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Biomedical subjects

H Griffiths

Publications and source records attributed to H Griffiths.

At least 37 records · Page 2Linked to original sources

Tissue spectroscopy with electrical impedance tomography: computer simulations.

A method is proposed by which bioelectrical spectroscopy could be combined with electrical impedance tomography (EIT) to provide noninvasive characterization of tissue. Multifrequency (2-200 kHz) EIT measurements were simulated with a numerical model for a volume of porcine liver immersed in an electrolytic tank. From the reconstructed EIT images the tissue characterization method was then applied enabling a plot of complex resistivity to be drawn for any selected pixel in the image. Simulations were performed for a small volume of degraded tissue embedded in the normal tissue to examine its effect on the derived spectroscopic parameters. The method could have an application in transplant surgery for screening organs for tissue degradation.

Animals

Avidity of specific IgG antibodies elicited by immunisation against Haemophilus influenzae type b.

AIM: To investigate the avidity of specific IgG polyribosyl ribitol phosphate (PRP) antibodies induced by three Haemophilus influenzae type b (Hib) conjugate vaccines: PRP-meningococcal outer membrane protein complex (PRP-OMP), PRP-non-toxic mutant diphtheria toxin, CRM197 (HbOC) and PRP-tetanus toxoid (PRP-T). METHODS: One hundred and ten infants were immunised with one of the vaccines at two, three and four months of age. Blood samples were taken after each vaccination and serum stored at -20 degrees C. Serum samples collected after the third course (that is, at five months of age) were submitted to antibody avidity assessment, using a urea enzyme linked immunosorbent assay (ELISA). RESULTS: All three conjugate vaccines elicited IgG PRP antibodies of high median avidity. The resultant antibody populations were heterogeneous with regard to avidity, which in turn was independent of PRP antibody concentration. CONCLUSIONS: With the recent findings of a correlation between bactericidal killing and affinity, our data highlight the need for a protective level to be expressed qualitatively as well as quantitatively.

Antibodies, Bacterial

Immunological factors and risk of infection in plateau phase myeloma.

AIMS: A series of patients with myeloma were investigated to assess whether immunological risk factors predisposing to serious infection could be identified. METHODS: Patients (n = 102) with predominantly plateau phase myeloma were monitored prospectively for infections. Immunological parameters including total non-paraprotein immunoglobulins and specific antibody titres were measured in all patients and compared with a control population of healthy individuals of a similar age; response to immunisation with Pneumovax II, tetanus and diphtheria toxoids and IgG subclasses were measured in a subgroup of 41 patients. Other characteristics investigated for any association with infection included age, sex, paraprotein type, disease stage, and chemotherapy. RESULTS: Specific antibody titres to pneumococcal capsular polysaccharides and tetanus and diphtheria toxoids were significantly reduced compared with the control population. Low antipneumococcal and anti Escherichia coli titres correlated with risk of serious infection and low anti-pneumococcal titres with severity of non-paraprotein immunosuppression. In 41 immunised patients responses to Pneumovax II, tetanus and diphtheria toxoids were poor; IgG subclass levels were significantly reduced and a poor IgG response to Pneumovax II immunisation was associated with an increased risk of septicaemia and low IgG2 levels. The overall serious infection rate was 0.92 infections per patient year and was four times higher during periods of active disease (1.90) compared with plateau phase myeloma (0.49). The predominant site of infection was the respiratory tract. Clinical and laboratory parameters showed only male sex and reduced non-paraprotein IgG and IgA levels to be significantly associated with at least one serious infection. CONCLUSIONS: A subgroup of patients with myeloma with poor IgG responses to exogenous antigens, who are at increased risk of serious infection, can be identified and may benefit from replacement immunoglobulin therapy to reduce the risk of infection.

Aged

Binding of anti-DNA antibodies to oxidatively damaged DNA in spouses and relatives of patients with systemic lupus erythematosus.

The prevalence of serum anti-DNA antibodies was evaluated by ELISA using oxidatively damaged DNA as antigen in 21 patients with systemic lupus erythematosus (SLE), in 9 spouses and in 15 first-degree relatives. These were compared with 12 healthy controls. There was no significant difference in the levels of serum antibodies detected between the group of spouses and normal controls with all results within the normal range of the assay. Binding of serum antibodies to the oxidatively damaged DNA was detectable in 12 (80%) of the relatives studied, and the range of values obtained overlapped significantly with the SLE patient group. The relevance of these antibodies to the immunopathology of SLE is unclear since they appear to be present in the absence of any clinical symptoms. However, they may be useful predictively as a marker for those individuals who are more likely to develop SLE.

Adolescent

Bioelectrical spectroscopy from multi-frequency EIT.

A method is described by which bioelectrical spectroscopy could be combined with multi-frequency electrical impedance tomography (EIT) enabling a Cole-Cole plot to be drawn for any selected pixel in the image for tissue characterization. To demonstrate the principles of the method, multi-frequency EIT measurements were simulated with a numerical model. As an example, porcine myocardium, immersed in an electrolytic tank, was simulated for a frequency range of 20 kHz to 2 MHz. The method could have an important application in transplant surgery for screening organs for viability prior to transplant.

Animals

An analysis of studies comparing electrical impedance tomography with x-ray videofluoroscopy in the assessment of swallowing.

Electrical impedance tomography can be used to record the conductivity change occurring in the neck during a swallow. X-ray videofluoroscopy provides excellent anatomical detail of the structures involved in swallowing and of the position of the swallowed bolus. The two techniques have been performed simultaneously on seven patients with swallowing problems to establish what produces the peak change in conductivity when a solution of low conductivity is swallowed. The results suggest that the exclusion of air from the larynx and pharynx is the major factor influencing the change in conductivity when a solution of low conductivity is swallowed.

Deglutition

A dosing scheme for carboplatin in adult cancer patients based upon pre-infusion renal function and platelet count.

The most important risk factors for the development of carboplatin-induced thrombocytopenia are total dose, glomerular filtration rate (GFR) and pre-infusion platelet count (P0). Pharmacokinetic and toxicity data from 23 patients with ovarian or testicular cancer were combined with published values from four other centers and the relationships between plasma clearance of ultrafilterable platinum and GFR, and between percentage reduction in platelet count and area under the plasma platinum curve were determined. The scatter in the data was estimated and used in a Monte-Carlo computer simulation to derive the following five-level dosing scheme. [table: see text] The scheme is based on 5% of patients incurring grade IV thrombocytopenia. Using this scheme, the majority of patients with ovarian or testicular cancer receiving carboplatin will be given an initial dose of 900 mg.

Adenocarcinoma

An investigation into the role of reactive oxygen species in the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity using neuronal cell lines.

The study of oxygen radical generation and effects during 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) metabolism was undertaken in an in vitro test system. Three neurochemically discrete neuronal cell lines, B50 (cholinergic) and B65 rat cell lines and SKNSH human neuroblastoma (both catecholaminergic), were exposed to MPTP (0-200 microM). Parallel experiments were performed using reagent H2O2, an intermediate which may be generated during MPTP metabolism, to determine whether MPTP and H2O2 had any selectivity of toxicity and whether the mechanisms of cell death were similar. MPTP toxicity was shown to be reduced by monoamine oxidase B inhibitors, pargyline (P < 0.01) and selegiline (P < 0.05), indicating that toxicity was due to metabolism of MPTP rather than the parent compound. Cytotoxicity was also decreased in the presence of antioxidants, most notably in the presence of superoxide dismutase and catalase together (P < 0.01), suggesting that reactive oxygen species (ROS) play a role in MPTP-induced cell death. Attempts to determine the intracellular target for oxidative attack did not identify significant levels of lipid peroxidation products, but did demonstrate nucleoid expansion, possibly the result of double stranded DNA breaks induced by ROS.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Actions of extracellular chloride ion substitution on contractility of isolated ventricular myocardium.

OBJECTIVE: Replacement of extracellular chloride ions by some other anions exerts a positive inotropic effect on isolated cardiac muscle preparations. The aim of this study was to determine whether the increase of force was mediated by an intracellular alkalosis. METHODS: Isometric tension development was measured using guinea pig papillary muscles during replacement of superfusate Cl- with isethionate ions. Intracellular pH and L-type Ca2+ currents were measured in isolated myocytes using epifluorescence microscopy and a switch-clamp technique respectively. RESULTS: Reduction of extracellular Cl- increased tension, a phenomenon which was partially inhibited with the anion exchange blocker SITS. Force was also increased by reducing superfusate PCO2. Reduction of superfusate [Cl-] and PCO2 both produced concentration dependent intracellular alkalosis. The relationship between the changes to tension and intracellular pH was different when either the superfusate [Cl-] or PCO2 was reduced, less pronounced when the [Cl-] was reduced. An increase of the L-type Ca2+ current was produced in low [Cl-] solutions which could be attributed to the accompanying intracellular alkalosis. CONCLUSIONS: The positive inotropic effect of superfusate Cl- removal can only partially be explained by intracellular alkalosis. Other, as yet unknown, changes must determine the remainder of the inotropic response.

Animals

Haemophilus influenzae type b carriage and immunity four years after receiving the Haemophilus influenzae oligosaccharide-CRM197 (HbOC) conjugate vaccine.

Late in 1991, before the implementation of a national immunization program against Haemophilus influenzae type b (Hib) in the United Kingdom, we performed a 4-year follow-up of 120 children who in 1987 had been enrolled in an immunogenicity trial in which 60 of them (vaccinees) received an Hib conjugate vaccine (HbOC) at the same time as diphtheria-tetanus toxoid-pertussis vaccine at the ages of 3, 5 and 9 months. Sixty others (controls) received only diphtheria-tetanus toxoid-pertussis vaccine at the same ages and were not subsequently immunized against Hib. We investigated Hib pharyngeal colonization using the antiserum agar method and the concentrations of serum IgG antibody to the type b capsule by enzyme-linked immunosorbent assay. At 4 years of age the Hib colonization rates in vaccinees and controls were 8% (5 of 60) and 5% (3 of 60), respectively. The children colonized with Hib had greater serum anti-capsular IgG concentrations than did noncolonized children (P < 0.001), and colonized vaccinees tended to have higher concentrations than colonized controls (P = 0.053). Regardless of Hib colonization status vaccinees had greater antibody concentrations than controls (P < 0.001). Forty-nine percent of vaccinees had an antibody concentration > 1 microgram/ml. There was an inverse relationship between the Hib colony count on culture and the serum IgG concentration. These data indicate that the increase in serum antibody concentration after immunization with an Hib conjugate vaccine is sustained and that immunization primes for a booster response on exposure to Hib. There may be a relationship between previous Hib conjugate immunization and the density of Hib colonization in children.

Antibodies, Bacterial

Dentine hypersensitivity: the measurement in vitro of streaming potentials with fluid flow across dentine and hydroxyapatite.

Stimulus transmission across dentine, in conditions such as dentine hypersensitivity, is considered to occur via a hydrodynamic mechanism. This fluid flow in dentine may then induce a mechanoreceptor response in pulpal nerves. However, when fluid flows through a porous structure electrical potentials are also generated. The aim of this study was to develop a reproducible model system to measure streaming potential across dentine and hydroxyapatite and determine the influence of pressure. Using an acrylic cell, with silver electrodes, streaming potentials were recorded across dimensionally standardized dentine and hydroxyapatite specimens, over a pressure range of 1-6 atmospheres. Streaming potentials were found to be directly proportional to pressure and dependent on the electrical conductivity of the saline used in the cell. The results confirm the limited existing data on streaming potentials across dentine and indicate that at these low pressures excitation of pulpal nerves would not occur. However, if, as may be the case, stimuli applied to dentine create very high pressures, the resultant potentials generated could indeed evoke a neural response. The model system is worthy of further use to study this phenomenon and the factors which may influence it.

Dentin

Effect of beta propiolactone on specific antibody measurements by ELISA.

Serum samples from 30 HIV seronegative patients were treated with beta propiolactone (BPL) to determine whether BPL interfaces with ELISA for specific antibodies against protein and carbohydrate antigens. BPL had no discernible effect on specific antibody measurements by ELISA. With the measuring need for specific antibody measurements in the management of HIV seropositive patients, it is reassuring that this laboratory safety measure does not impair the reliability of results.

Antibodies, Bacterial

The incidence of deep-vein thrombosis after upper tibial osteotomy. A venographic study.

We performed postoperative venography on 84 consecutive patients who had undergone upper tibial osteotomy for medial compartment osteoarthritis of the knee. Deep-vein thrombosis was demonstrated in 41%. Only 15% of the cases were diagnosed clinically, all in the calf veins. Cases of proximal thromboses (3) and mixed-vein thromboses (12) were only revealed by venography.

Adult

Morphologic changes in the human patellar tendon after bone-tendon-bone anterior cruciate ligament reconstruction.

Magnetic resonance imaging (MRI) was performed on 15 patients, an average of 2.5 years after arthroscopically assisted bone-tendon-bone (BTB) anterior cruciate ligament (ACL) reconstruction, to evaluate the patellar tendon donor site. Five patients who had arthroscopically assisted ACL reconstruction using the semitendinosus tendon as a graft also were scanned bilaterally and evaluated. The mean difference between the involved and uninvolved patellar tendon length was -0.2 mm for the BTB patients and -2.6 mm for the semitendinosus patients. The mean difference between patellar tendon width for the BTB patients was 1.1 mm and 1.9 mm for the semitendinosus patients. The mean difference between patellar tendon thickness was 0.4 mm for the BTB surgery group and 0.02 mm for the semitendinosus surgery group. None of the differences were statistically significant. Results indicate that harvesting the central one third of the patellar tendon does not significantly affect the length, width, or thickness of the tendon at least 22 months after arthroscopically assisted BTB-ACL.

Adolescent