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Biomedical subjects

H Griffiths

Publications and source records attributed to H Griffiths.

At least 19 recordsLinked to original sources

Antipolysaccharide antibodies in 450 children with otitis media.

We have measured antibodies to pneumococcal and Haemophilus polysaccharides in a prospective study of 450 children aged 2-16 years with otitis media requiring grommets (ear tubes). Pneumococcal antibody levels were significantly higher in the 2-6 year (P < 0.004) and 7-10 year (P < 0.04) study groups in comparison with age-matched controls. There was no difference in Haemophilus antibody levels between the study and control group children for the age groups 2-6 years and 11-16 years. Haemophilus antibody levels were significantly lower in the 7-10 year (P < 0.003) group in comparison with age-matched controls. Eighty-eight out of 450 (19.6%) children had pneumococcal antibody levels below the 25th percentile. Nineteen out of 88 (21.6%) children with pneumococcal antibody levels below the 25th centile were test immunized with 23 valent Pneumococcal polysaccharide and unconjugated Haemophilus type b capsular polysaccharide. Of these 19 children (aged 4-11 years), five mounted suboptimal responses to both polysaccharide antigens, whilst one child failed to respond to Haemophilus polysaccharide alone. There was no significant difference in the prevalence of IgG subclass deficiency between the normal responders and poor responders to immunization (P = 0.12). We found no evidence of specific polysaccharide antibody deficiency in the vast majority of the 450 children studied. However, the significance of poor antibody responses to test immunization in a small minority of children with otitis media is unclear. Long-term follow up of these children is required to determine whether poor immunization responses herald the development of frank antibody deficiency.

Antibodies, Bacterial

Simultaneous electrical impedance tomography and videofluoroscopy in the assessment of swallowing.

Simultaneous videofluoroscopy and electrical impedance tomography (EIT) were performed in 13 patients. Subjects swallowed a low-conductivity and a higher-conductivity bolus of between 5 and 20 ml. EIT images from the two swallows were then subtracted to cancel out movement related changes. The peak in the conductivity change was most closely associated in time with a point at which the pharynx is filled with bolus: this suggests that the subtraction process does produce data and images which are related to the bolus rather than to movement of involved structures. The full width at 50% and 75% of the maximum of the time conductivity plot was correlated with the time taken for the bolus to be cleared from the mouth (r = 0.63 and 0.68 respectively, p < 0.05 for both). Despite the sampling frequency of only 9 frames s-1, compared to 50 frames s-1 for videofluoroscopy, EIT recordings from the neck are able to detect the presence of a conductive bolus in the pharynx and for the first time the relationship between parameters of an EIT time-conductivity plot and a measure of bolus transit using an accepted technique has been established.

Adult

An electrical impedance tomography microscope.

A circular array of 16 electrodes has been constructed for use as an electrical impedance tomography (EIT) microscope. The electrodes were made from 60 microns diameter gold wires anchored to a printed circuit board. The internal diameter of the array was 0.9 mm giving a theoretical spatial resolution of about 100 microns. For EIT imaging, the array was connected to an imaging system operating at 82 kHz. Static images of conducting and insulating filaments (cooper wire and human hair) in saline solution were obtained as well as dynamic imaging sequences of glass microspheres migrating through the array. The interelectrode impedance was typically 5 k omega and the transimpedances ranged from 14 to 210 omega.

Electric Impedance

EITS changes following oleic acid induced lung water.

We present the results of using electrical impedance tomographic spectroscopy (EITS) to follow the changes in lung water induced by oleic acid. Measurements were made on three goats before and after the injection of oleic acid. In addition to the EITs measurements, lung water was also measured using a double-indicator technique. Large falls in lung electrical impedance were seen as a result of the increase in lung water but the size of the fall was a function of the frequency at which the measurements were made. These changes have been modelled using the Cole equation. Four-electrode measurements were also made on two extracted porcine lungs and Cole equation modelling carried out following the introduction of saline into the lungs. Results were similar in the two sets of animal experiments.

Animals

Persistence of antibody responses to Haemophilus influenzae type b polysaccharide conjugate vaccine in children with vertically acquired human immunodeficiency virus infection.

BACKGROUND: Recurrent bacterial sepsis is common in pediatric HIV infection and immunization against Haemophilus influenzae type b (Hib) is recommended. Long term persistence of anti-Hib antibody and the need for, or timing of, a booster dose has not been adequately studied. METHODS: Immunogenicity during a 12-month period following immunization with Hib-tetanus conjugate vaccine (ACT-HIB; Merieux) was evaluated in 48 vertically HIV-infected children and 36 uninfected children, born to HIV-positive mothers. A titer of anti-Hib polysaccharide antibody of > or = 0.15 microgram/ml was considered to indicate short term and > or = 1 microgram/ml long term protection. RESULTS: At 1 month postvaccination 36 (100%) uninfected and 42 (88%) HIV-infected children achieved titers of > or = 1 microgram/ml. However, by 1 year titers had dropped below this value in 18 (43%) infected compared with only 4 (11%) uninfected children (chi square, 9.7; P = 0.002). Although the rate of fall of antibody titer was greater in uninfected than in infected children, this was no longer the case after adjustment for the 1-month postimmunization titer. The rate of antibody titer decline was not significantly related to HIV disease status or to either the age-related CD4 count at the time of immunization or the change in age-adjusted CD4 count during the 12 months after immunization. CONCLUSIONS: Not only was the initial antibody response to Hib conjugate vaccine decreased in children with HIV infection and AIDS but also 1 year later only 57% of the initial responders had persisting titers above the level associated with long term protection. The need for reimmunization of children with HIV infection against Hib requires further evaluation.

AIDS-Related Opportunistic Infections

Haematological and acute-phase responses associated with delayed-onset muscle soreness in humans.

Delayed-onset muscle soreness following unaccustomed or eccentric exercise is associated with inflammation, tissue necrosis and the release of muscle enzymes (Newham et al. 1983). We have investigated the time course of changes in circulating leucocytes and serum levels of some acute phase reactants, serum creatine kinase activity (CK) and muscle pain after a 40-min bout of bench-stepping exercise in eight healthy untrained subjects. Leg muscle soreness was greatest 2 days after the exercise bout. Peak serum CK values [mean (SD) 540 (502) IU.1-1] occurred 1-7 days post-exercise. Serum C-reactive protein (CRP) was unchanged from pre-exercise levels [7.8 (3.4) mg.1-1] immediately post-exercise [7.9 (2.3) mg.1-1] but rose to a peak of 17.0 (3.9) mg.1-1 1 day post-exercise, thereafter declining to basal levels. Serum levels of iron and zinc fell below pre-exercise levels for 1-3 days post-exercise. Serum albumin, IgG and IgM fell below pre-exercise levels from 1 day post-exercise, reaching minimal values (about 80% of basal levels) at 7 days post-exercise. The exercise did not appear to significantly affect serum levels of alpha-1-antitrypsin and alpha-1-acid glycoprotein. Two and three days after the exercise bout the circulating numbers of total leucocytes, neutrophils, monocytes and basophils fell 15-20% below pre-exercise levels, whereas lymphocytes, eosinophils and platelets were unchanged. The results indicate that a rapid acute phase inflammatory response is initiated within 1 day of a bout of exercise that induces delayed-onset muscle soreness, and that any later tissue necrosis that may occur is not accompanied by further marked changes in acute-phase reactants such as CRP.

Acute-Phase Proteins

Antibody responses and symptoms after DTP and either tetanus or diphtheria Haemophilus influenzae type B conjugate vaccines given for primary immunisation by separate or mixed injection.

The safety and immunogenicity of two conjugate Haemophilus influenzae type B (Hib) vaccines administered either mixed with, or in separate limbs to, a whole-cell DTP vaccine, was compared in infants vaccinated at 2, 3 and 4 months of age. Antibody titres to purified polyribosylribitol phosphate, diphtheria, and to pertussis antigens between infants who received the Hib and DPT vaccines in separate limbs or in the same limbs were similar (P > 0.1) while antibody titres to tetanus toxoid were higher in the later group (P < 0.05). This study demonstrated that both Hib vaccines can be mixed with whole-cell DTP vaccine without reducing immunogenicity of either vaccine or increasing the incidence of adverse reactions.

Antibodies, Viral

A Cole phantom for EIT.

A phantom was designed for testing and comparing multifrequency EIT data collection systems. The phantom simulates a cylinder of homogeneous conductor with 16 drive and 16 receive electrodes interleaved. Combinations of resistors and capacitors were used to simulate the complex impedance, Z*, of a typical tissue in the frequency range 8-2048 kHz obeying the Cole equation Z* = Z infinity + (Z0 - Z infinity)/[1 + (if/fc)(1- alpha )] where Z* is the complex impedance at frequency f, Z0 and Z infinity are the limiting values of impedance at low and high frequencies, fc is the characteristic frequency and alpha is a constant. A practical phantom was then constructed on which four different sets of spectroscopic parameters could be selected: (i) alpha = 0.20, fc = 150 kHz, Z0/Z infinity = 3.31; (ii) alpha = 0, fc = 273 kHz, Z0/Z infinity = 2.64; (iii) alpha = 0, fc = 71.1 kHz, Z0/Z infinity = 1.36; and (iv) Z0/Z infinity = 1.00 with no dispersion.

Electric Impedance

The repeatability and variability of electrical impedance tomography indices of pharyngeal transit time in normal adults.

Two electrical impedance tomography (EIT) indices of pharyngeal transit time have been repeatedly measured in 20 normal adults. The time course of change in pharyngeal conductivity whilst swallowing 5, 10 and 20 ml boluses was expressed either as a full width at 20% maximum (FW20) or as a full width at 50% maximum (FW50): the latter could be satisfactorily measured more frequently. Mean coefficients of variation for FW20 and FW50 tended to decrease with increasing bolus volume but this was statistically significant only for FW50 in men. FW20 and FW50 were significantly shorter in men than women and increased with increasing age. FW50 was significantly smaller when larger bolus volumes were swallowed. FW50 was significantly shorter when low-conductivity fluid was used and there was an insignificant trend for it to be longer with electrodes in the highest position. The amplitude of the conductivity change recorded was significantly affected by all factors studied apart from age. If EIT is to be used as a technique for monitoring changes in pharyngeal transit time in patients with neurogenic dysphagia, repeat examinations should be performed under the same conditions and, if possible, large bolus volumes should be used.

Adult

Antibody responses to Haemophilus influenzae type b and Streptococcus pneumoniae vaccines in children with human immunodeficiency virus infection.

Antibody responses to Haemophilus influenzae type b (Hib) conjugate (ActHIB; Pasteur Merieux) and pneumococcal (Pneumovax II; Morson) vaccines were measured in 56 infected children (VI) and 44 uninfected children (U) older than 18 months of age, born to human immunodeficiency virus-positive mothers. Preimmunization, 21% U and 20% VI had protective concentrations of anti-Hib polysaccharide antibodies. Postimmunization, 100% U and 86% VI achieved protective titers (P = 0.008). The geometric mean increase in anti-Hib polysaccharide antibody was 7.6 (95% confidence interval, 3.5 to 16.3; P = 0.0001) times higher in U than in VI children after adjusting for age and ethnicity. Sixty-one percent U compared to 54% VI showed a 2-fold increase in antibody levels to at least one of the four pneumococcal vaccine serotypes (3, 6, 19, 23) measured (P = 0.4). For both vaccines there was a significant trend toward poorer responses in children with acquired immunodeficiency syndrome but no correlation with age adjusted CD4 counts. These data suggest that human immunodeficiency virus-infected children should be immunized with these polysaccharide vaccines early in the course of their disease.

Antibodies, Bacterial

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