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Biomedical subjects

A Spencer

Publications and source records attributed to A Spencer.

At least 55 records · Page 3Linked to original sources
PubMed1998

Postoperative hypoxaemia: continuous extradural infusion of bupivacaine and morphine vs patient-controlled analgesia with intravenous morphine.

We carried out a randomized prospective study in 60 patients who had undergone major abdominal surgery for cancer. For postoperative pain control, 30 patients received continuous extradural infusion of 0.125% bupivacaine 12.5 mg h-1 and morphine 0.25 mg h-1 (EXI group) and 30 received patient-controlled analgesia (PCA) with intravenous morphine (1 mg bolus, 5-min lock-out and maximum dose 20 mg 4h-1). Both groups had general anaesthesia. The two groups were compared for postoperative pain scores, satisfaction, sedation and oxygen saturation. Oxygen saturation was recorded continuously the night before surgery and for two consecutive postoperative nights. Episodes of moderate desaturation (90% > SpO2 85%) were more frequent in the EXI group than in the PCA group (P < 0.05). Pain scores were lower in the EXI group compared with the PCA group at rest and while coughing (P < 0.05). No significant difference was found for patient sedation and satisfaction.

Abdominal Neoplasms↗
PubMed1998

Emmetropisation, axial length, and corneal topography in teenagers with Down's syndrome.

AIM: To study the refractive status and corneal topography in Down's syndrome. METHOD: A matched cohort subgroup of 50 individuals with Down's syndrome in the Manchester area aged 15-22 years was studied by refraction, corneal topography, A-scan biometry, slit lamp examination, and orthoptic examination. RESULTS: (1) A linear relation was found between axial length and spherical equivalent refraction. There was no statistical relation between keratometry and the axial length. (2) 80% of the group had a hyperopic refraction (mean +2.46 D, range +0.5 to +7.5 D); 18% were myopic (mean -2.75 D, range -0.5 to -8.0 D); and 2% were emmetropic (within plus or minus 0.5 D of zero). The overall mean spherical equivalent refraction was +1.43 (SD 2.86) D. 63% of eyes could see 6/12 or better and 66% of the individuals had a binocular vision of 6/12 or better. (3) Corneal topography was generally of a regular "bow tie" pattern, but there was a high incidence of oblique cylinders. Mean cylinder strength was 1.14 (1.15) D. (4) The prevalence of overt keratoconus was 2%. 6% had corneal topography with inferior steepening which may be a preclinical keratoconic process. CONCLUSIONS: In this cohort of late teenagers with Down's syndrome, emmetropisation has failed to occur in most individuals. In a similar aged group of non-disabled individuals one would expect about 83% emmetropic (plus or minus 0.25 D), 13% myopic, and 4% hyperopic. The wide spread of oblique cylinders and the small proportion of with the rule astigmatism is probably related to this failure of emmetropisation. The prevalence of 2% keratoconus in Down's syndrome compares with that found by other authors of between 5.5 and 15%. The 6% with inferior steepening on topography will be followed up over the next few years to see if there is any development of clinical keratoconus. Hence we will see if corneal topography is useful as a screening tool for preclinical keratoconus in this high risk group.

Adolescent↗
PubMed1998

Gadolinium chloride toxicity in the mouse.

1. Groups of five male and five female CD-1 mice received a single intravenous injection of gadolinium chloride at dosages of 0 (saline control), 0.05, 0.1 and 0.2 mmol/ kg. All mice were necropsied 48 h post dose. 2. Plasma analysis showed increases in concentrations of lactate dehydrogenase (both sexes), aspartate aminotransferase and alanine aminotransferase (females only) in the 0.2 mmol/kg group. Cholesterol was elevated at all dosages in both sexes whilst globulin was raised in both sexes at 0.1 and 0.2 mmol/kg. 3. Histological lesions were present at all dosages and increased in severity in a dose-related fashion. The most common lesions were: mineral emboli in capillaries, accumulation of mineral in the mononuclear phagocytic system, hepatocellular necrosis, and lymphoid depletion, necrosis and mineralisation in the spleen. 4. Such observations are similar to those in rats given gadolinium chloride and should be assessed when evaluating the toxicological profile of gadolinium containing compounds being developed for nuclear magnetic resonance imaging.

Alanine Transaminase↗
PubMed1997

Structural and dynamical properties of a denatured protein. Heteronuclear 3D NMR experiments and theoretical simulations of lysozyme in 8 M urea.

Oxidized and reduced hen lysozyme denatured in 8 M urea at low pH have been studied in detail by NMR methods. 15N correlated NOESY and TOCSY experiments have provided near complete sequential assignment for both 1H and 15N resonances. Over 900 NOEs, including 130 (i, i + 2) and 23 (i, i + 3) NOEs, could be identified by analysis of the NOESY spectra of the denatured states, and 3J(HN, Halpha) coupling constants and 15N relaxation rates have been measured. The coupling constant and NOE data were analyzed by comparisons with theoretical predictions from a random coil polypeptide model based on amino acid specific phi,psi distributions extracted from the protein data bank. There is significant agreement between predicted and experimental NMR parameters suggesting that local conformations of the denatured states are largely determined by short-range interactions within the polypeptide chain. This result is supported by the observation that the chemical shift, coupling constant, and NOE data are little affected by whether or not the four disulfide bridge cross-links are formed in the denatured protein. The relaxation data, however, show significant differences between the oxidized and reduced protein. Analysis of the relaxation data in terms of simple dynamics models provides evidence for weak clustering of hydrophobic groups near tryptophan residues and increased barriers to motion in the more compact conformers formed when the polypeptide chain is cross-linked by the disulfide bridges. Using this information, a structural description of these denatured states is given in terms of an ensemble of conformers, which have a complex relationship between their local and global characteristics.

Amino Acid Sequence↗
PubMed1997

Paranasal sinusitis following allogeneic bone marrow transplant.

In attempt to identify major clinical features of paranasal sinusitis following allogeneic BMT, we reviewed 44 consecutive cases diagnosed at the Hammersmith Hospital between August 1993 and December 1995. All patients had symptoms and signs characteristic of sinusitis. Plain radiographs and/or CT scans revealed fluid levels in 86.4% of patients, opacification in 9.1%, and marked mucosal thickening in 4.5%. Two-thirds of patients were diagnosed within 120 days of BMT. The WBC was less than 1 x 10(9)/1 in 16.3% of patients, the neutrophil count was less than 0.5 x 10(9)/1 in 18.6%, and serum immunoglobulins were depressed (< 6.7 g/l) in 40.6%. Grade III-IV acute GVHD was present in 25.6% of patients and grade I-II in 66.7%; 68.6% developed chronic GVHD. There were 70.5% of patients receiving corticosteroids. Specific pathogens could not be identified in most cases. Pneumonia was present in 10 patients, seven of whom had Aspergillus species identified by bronchoalveolar lavage. Parainfluenza virus was isolated in three patients and Pseudomonas aeruginosa in two. Although all patients received antimicrobial therapy, 70.5% developed chronic sinusitis. Fatal complications did not occur. In 94 consecutive patients receiving allografts for CML during the period of study, WBC and neutrophil counts were lower 3 months post-BMT in patients who developed sinusitis (P < 0.02). Patients receiving higher doses of total body irradiation (13.2 and 14.4 Gy) had a greater probability of developing sinusitis (P = 0.023). Sinusitis occurred in only one of 37 patients receiving autologous transplants in the same period. Sinusitis is common following allogeneic BMT. Leukopenia is often present, but microbiological diagnosis is difficult, and progression to chronic sinusitis common.

Adolescent↗
PubMed1997

Clonal instability preceding lymphoid blastic transformation of chronic myeloid leukemia.

We have sought the presence of rearrangements of the immunoglobulin heavy chain gene locus in 13 patients with chronic myeloid leukemia (CML) in lymphoid blastic transformation (L-BT) using the polymerase chain reaction (PCR). The lymphoid nature of the transformation was confirmed by immunophenotyping and/or Southern blot hybridization with a J(H) probe. Clonal rearrangements were detected in 85% of cases and two or more rearrangements were visible in 64% of informative cases. The pattern of V(H) gene family utilization revealed an apparent reduction in V(H)4 family gene usage but otherwise reflected the known proportion of each gene family in the germline repertoire. In six cases the third complementary determining regions (CDR3) of the predominant blast crisis clone/s were sequenced revealing minimal evidence of somatic mutation. No clonal changes were detected in the chronic phase leukemia cells collected more than 6 months before the onset of L-BT in three of these patients. Of the other three patients studied in chronic phase from 1 to 6 months before L-BT, two showed clonal rearrangements which differed in size from those present at L-BT. In one patient a V(H)3 to V(H)5-D(H)-J(H) substitution had occurred at least 3 months prior to L-BT. In the other patient, however, the sequence of the rearrangement present 5 months prior to L-BT was unrelated to the rearrangements at the time of L-BT indicating a pattern of clonal succession. We conclude that: (1) IgH gene rearrangements are detectable in the majority of patients with L-BT using PCR and the lymphoid lineage of blastic CML is most readily confirmed using consensus primers to the framework 3 region; (2) somatic mutation is uncommon; and (3) B lymphoid clones distinct from those identified later may be detected before overt lymphoid BT. The identification of such 'abortive' clones is evidence for clonal instability before the onset of transformation and might have prognostic value.

Adolescent↗
PubMed1997

BCR/ABL-negative progenitors are enriched in the adherent fraction of CD34+ cells circulating in the blood of chronic phase chronic myeloid leukemia patients.

Philadelphia chromosome-positive (Ph+) hemopoietic cells predominate in patients with chronic myeloid leukemia (CML) in chronic phase, but some Ph presumably normal stem cells persist in most patients. Ph cells are relatively frequent, compared to mature cell populations, in primitive hemopoietic cell populations from CML patients. We have purified CD34+ cells from chronic phase CML blood and separated them into two fractions on the basis of adherence or non-adherence to tissue culture plastic. We also separated CD34+ CML cell populations into HLA-DR(hi) and HLA-DR(lo) fractions and CD38(hi) and CD38(lo) fractions by flow cytometry. The CD34+ cells that adhered to plastic were predominantly CD33-, CD38- and HLA(-)-DR; cells with these phenotypic properties were significantly rarer in the CD34+ non-adherent cell population (P = 0.008-0.02). Expression of p210 BCR/ABL mRNA by adherent, non-adherent, HLA-DR(hi) and HLA-DR(lo)CD34+ cell subpopulations was demonstrated by RT-PCR. Using fluorescence in situ hybridization (FISH) in conjunction with BCR and ABL probes we detected Ph+ and Ph- cells in both adherent and non-adherent CD34+ cell fractions of 15/15 patients studied and in the HLA-DR(lo) or CD38(lo) sorted CD34+ cell fractions. The concentration of Ph- cells in the adherent CD34+ cell fraction was three-fold higher than in the non-adherent fraction (P = 0.001). Ph- adherent cells were detected in untreated CML patients and as late as 6 years after diagnosis of CML in patients treated with hydroxyurea (HU) or interferon-alpha (IFN-alpha). We conclude that whilst appreciable numbers of Ph- primitive hemopoietic progenitors are present in the circulation in untreated patients and also in treated patients in late chronic phase, the majority of cells expressing CD34 but not CD33, CD38 or HLA-DR antigens, are part of the CML clone.

Adult↗
PubMed1997

Primers for exon-specific amplification of the KRT5 gene: identification of novel and recurrent mutations in epidermolysis bullosa simplex patients.

The KRT5 and KRT14 genes encode the proteins keratin 5 and 14, respectively, which are the primary structural components of the 10-nm intermediate filaments of the mitotic epidermal basal cells. A single mutation in either gene can disrupt the keratin intermediate filament cytoskeleton, resulting in the skin fragility and blistering that is characteristic of the group of inherited disorders known as epidermolysis bullosa simplex. We have established a mutation detection system that facilitates KRT5 gene analysis from leukocyte genomic DNA, obviating the need for a skin sample or keratinocyte culture for cDNA synthesis. KRT5 intronic regions that flanked each exon were sequenced and sets of facing intronic primers were designed for specific amplification of each of the nine KRT5 exons. Direct sequencing of KRT5-amplified exons identified three novel missense mutations. One mutation recurred in two unrelated patients with sporadic EBS. This glutamate to lysine substitution (E477K), located in the highly conserved KLLEGE motif at the end of the central rod domain, is the third recurrent mutation identified in dominant epidermolysis bullosa simplex disease. The corresponding glutamate in keratin 2e was previously reported to be frequently mutated in ichthyosis bullosa of Siemens, suggesting that this highly conserved residue may be a potential mutational hot spot in other type II keratins or nonkeratin intermediate filament proteins.

Alleles↗
PubMed1996

Quantitation of mafosfamide-resistant pre-colony-forming units in allogeneic bone marrow transplantation: relationship with rate of engraftment and evidence for long-lasting reduction in stem cell numbers.

Current assays of human committed-stem cells are of limited value in predicting the rate of engraftment or in assessing the integrity of the stem cell pool after allogeneic bone marrow (BM) transplantation (BMT). We have used a limiting dilution assay of mafosfamide-resistant progenitors (pre-colony-forming units [CFU]), which are ancestral to committed progenitors such as CFU-granulocyte-macrophage (GM) to analyze the kinetics of myeloid engraftment after BMT and to assess the size of the stem cell pool at intervals up to 66 months thereafter. In 24 patients transplanted for chronic myeloid leukemia in chronic phase (eight with matched unrelated donors and 16 with sibling donors), the rate of neutrophil engraftment correlated strongly with the number of pre-CFU transfused per kilogram recipient body weight (r = .7, P < .005) but not with CFU-GM per kilogram or nucleated cells per kilogram. In 25 patients studied 6 to 66 months after allogeneic BMT, the mean number of pre-CFU in the marrow was 3.1/10(5) mononuclear cells (MNC) (median, 3.47; range, 0.4 to 23.3), compared with 24.7/10(5) MNC (median, 27.3; range, 4.2 to 180) in 25 normal subjects. CFU-GM were also reduced in these patients, but with considerable overlap into the normal range (mean +/- SD: 54 +/- 45.6 per 10(5) MNC; normal, 129 +/- 61.6). Low pre-CFU but not low CFU-GM levels were associated with reduced peripheral blood white blood cell counts in post-BMT patients. Pre-CFU and CFU-GM levels were not related to the interval posttransplant and remained low for up to 66 months. We conclude that the pre-CFU assay measures a population of stem/progenitor cells that are important in the kinetics of engraftment after allogeneic BMT. Our data suggest that pre-CFU levels may remain low for some years after BMT in humans.

Antineoplastic Agents↗
PubMed1996

Feasibility of neonatal lung imaging using electrical impedance tomography.

The feasibility of detecting the lungs in preterm babies using electrical impedance tomography (EIT) was investigated. A single frequency instrument using 16 electrodes to apply current and detect peripheral voltages was constructed. The instrument applied AC current of 1.5 mA peak-peak at a carrier frequency of 20 kHz. Images were reconstructed using a sensitivity-regions backprojection method. A 9-day-old preterm baby was tested and data were collected at a speed of 10 frames/s. A dynamic image showing the lungs at full inspiration referenced to expiration is illustrated in this paper. Impedance measurements taken across the chest during the first 2 s did not show a clear pattern thus demonstrating irregular breathing. Region of interest analysis were carried out on the reconstructed images and tracked with time. Fourier transforms were then performed on these signals and a fundamental frequency at 1 Hz, corresponding to normal breathing rate of 60 breaths/min, was detected. Harmonics of the signal caused distortion especially on the left lung where the effects of cardiac events were more dominant.

Electric Impedance↗
PubMed1996

Marginal costs and benefits.

Decision makers are interested in measuring the costs and benefits of various interventions, and sometimes they are presented with the average costs and benefits of alternative interventions and asked to compare these. Usually a newer intervention is being compared with an existing one, and the most appropriate comparison is not of average costs (and benefits) but of the extra--or marginal--costs (and benefits) of the new intervention. Reanalysis of the cost effectiveness ratio of biochemical screening of all women for Down's syndrome compared with age based screening shows that the marginal cost effectiveness of biochemical screening is 47,786 pounds, compared with an average cost effectiveness of 37,591 pounds. It may sometimes be difficult or costly to calculate marginal costs and benefits, but this should be done whenever possible.

Adult↗
PubMed1996

BCR-ABL-positive lymphoblastoid cells display limited proliferative capacity under in vitro culture conditions.

We studied the kinetics of EBV-transformed B-cell lines from patients with chronic myeloid leukaemia (CML) using RT-PCR for BCR-ABL transcripts and immunoglobulin heavy chain (IgH) gene rearrangements. Peripheral blood mononuclear cells, obtained from four patients with CML in chronic phase and from one in accelerated phase, were incubated with supernatant from the B95-8 EBV producing cell line. In 11/25 (44%) B-cell cultures established we demonstrated the presence of BCR-ABL transcripts at intervals ranging from 32 to 125 d post EBV transformation. In all but two cases, evidence of BCR-ABL transcripts disappeared with time. Cultures were initially polyclonal with respect to IgH rearrangements but became progressively oligoclonal, suggesting the longer-term survival of fewer clones, all of which were BCR-ABL negative. We conclude that BCR-ABL-positive lymphoid cultures can be established in the short term from the majority of patients with CML but they have limited capacity to survive in the longer term. Therefore, in lymphoid cells the presence of the BCR-ABL chimaeric gene appears to confer no survival advantage.

Cell Division↗
PubMed1996

Using consumer feedback to improve services.

Describes how a consumer satisfaction survey was carried out at a community mental health centre and the improvements that occurred as a result. A questionnaire was designed to be delivered as a semi-structured interview to elicit the views and opinions of the clients. Their responses highlighted a number of positive areas about the centre, especially in terms of the staff and the therapeutic support they provide. The feedback also revealed a number of areas where improvements were needed. Reports on six recommendations which were made in terms of medication, activities, privacy, reviews, social service issues and complaints. The staff worked hard to implement a number of changes to improve the quality of the service they provide. The end result is that users' views and opinions have been integrated with the service design and delivery, making the centre a more user-friendly place.

Community Mental Health Centers↗
PubMed1996

Pretreatment with controlled-release morphine for pain after hysterectomy.

In a double-blind randomised study, two dosing regimens for controlled-release morphine tablets were compared against placebo to ascertain the extent of prophylactic postoperative pain control in 51 women undergoing abdominal hysterectomy. One group of patients received controlled-release morphine every 12 h for 2 days before surgery, a second group received a single dose of controlled-release morphine 2 h before surgery and a third group received placebo. Patient-controlled analgesia system demands were compared for the first 38 h after surgery and 10-point pain scores and McGill pain questionnaires were compared for the first 6 postoperative days and at 6 weeks after surgery. During the first 2 days after surgery, patients reported high levels of pain which were similar in all groups. Pain scores on the third and fourth postoperative days were significantly lower in those who had a single pre-operative dose of controlled-release morphine compared with placebo and those who had been treated with-morphine every 12 h for 2 days (p = 0.043 and 0.024 for third and fourth day respectively). Patient-controlled analgesia demands were also fewer and less variable in those patients receiving the single dose of morphine 2 h before surgery. The study shows a beneficial analgesic effect of a single pre-operative dose of morphine, but shows no benefit for a more prolonged pre-operative dosing regimen.

Adolescent↗
PubMed1996

Pharmacological properties of voltage-gated Na+ currents in motor neurones from a hydrozoan jellyfish Polyorchis penicillatus

The Na+ current of 'swimming motor neurones' in the hydromedusan Polyorchis penicillatus was tetrodotoxin-insensitive. The local anaesthetics lidocaine and procainamide caused partial, non use-dependent blockade of the Na+ channel. Veratridine produced partial blockade of the Na+ channel without affecting inactivation. An order of blocking potency of di- and trivalent cations was established as: La3+ = Zn2+ = Cd2+ > Ni2+ > Mn2+ = Co2+ > Ca2+ > Ba2+ > Mg2+. All these cations, except Ba2+, produced depolarizing shifts in the conductance-voltage curves. Even at relatively high concentrations, the dihydropyridines nicardipine, nitrendipine and (+)Bay K 8644 produced only weak blockade of the Na+ current; while nimodipine, nifedipine and (-)Bay K 8644 were ineffective. Diltiazem and verapamil weakly blocked the Na+ current in a dose-dependent manner with no evidence of use-dependence. The calmodulin inhibitors W7 and calmidazolium were ineffective blockers of Na+ currents. Crude Conus venoms and the Conus peptides, &micro;-conotoxin GIIA, &micro;O-conotoxin MrVIA, omega-conotoxin GVIA and omega-conotoxin MVIIC, were without effect. Capsaicin produced rapid, reversable blockade of Na+ current. It has been suggested that 'primitive' Na+ channels could be expected to have pharmacological properties that are intermediate between those of Na+ and Ca2+ channels. If such channels exist, the Na+ channel described here is clearly not one of them.

Journal Article↗
PubMed1996

Expression of the LH2 gene in chronic myeloid leukaemia cells.

The LH2 gene encodes a putative transcription factor containing two N-terminal LIM and one C-terminal HOX domains. The LH2 locus was mapped to 9q33-34.1, centromeric to the ABL gene. In a recent report, it was suggested that high levels of LH2 expression are consistently observed in chronic myeloid leukemia (CML) patients, whereas no transcription is detected in normal individuals. This led to the hypothesis that aberrant expression of LH2 may represent an additional mechanism for malignant cell proliferation in CML. We have studied the expression of LH2 in leucocytes from patients with CML or with other chronic myeloproliferative disorders (CMD), and from normal individuals, using an optimised reverse-transcription and polymerase chain reaction (PCR) technique. Twenty-seven out of 29 cDNA samples from normal individuals (93%), 49 out of 51 samples from CML patients (96%) and 20 out of 20 from Philadelphia chromosome-negative CMD showed evidence of LH2 expression. Similarly, LH2 transcription was also detected in leucocytes from CML patients in complete cytogenetic remission after treatment with interferon-alpha. Furthermore, all 36 EBV-induced lymphoblastoid cell lines established from six chronic phase CML patients showed unequivocal LH2 expression, regardless of the BCR-ABL status of the line (9 BCR-ABL positive, 27 BCR-ABL negative). We conclude that LH2 expression is not confined to CML cells, and that the t(9;22)(q34;qll) does not promote 'de novo' transcriptional activation of this gene.

Base Sequence↗