Biomedical subjects

D Charlton

Publications and source records attributed to D Charlton.

11 recordsLinked to original sources

PubMed2000

Pre-existent adenovirus antibody inhibits systemic toxicity and antitumor activity of CN706 in the nude mouse LNCaP xenograft model: implications and proposals for human therapy.

Pre-existent humoral antibody to adenovirus potentially confounds human clinical trials involving intravascular administration of adenovirus. Using the LNCaP prostate cancer xenograft model in BALB/c nu/nu mice and the prostate-specific attenuated replication-competent adenovirus (ARCATM) CN706, we developed an animal model that systematically controls both the dose of intravascularly administered adenovirus and the titer of the pre-existent anti-Ad5 antibody, and then measures the virus-induced toxicity as well as antitumor activity. We prepared hyperimmune sera to adenovirus in rabbits, passively injected the purified rabbit anti-Ad5 antibody into tumor-bearing mice, and established measurable humoral anti-Ad5 antibody titers. CN706 was intravenously injected into the tail vein of animals 24 hr after passive anti-Ad5 antibody administration. In the absence of pre-existent antibody, the lethal dose (LD100) for BALB/c nu/nu mice was 2.5x10(11) CN706 particles, whereas 1x10(11) CN706 particles was not lethal. However, in the presence of a 1:80 pre-existent titer of Ad5 neutralizing antibody (NAb), intravenous injection of 5x10(11) CN706 particles was no longer lethal. In addition, pre-existent antibody also prevented antitumor activity in a dose-dependent manner: 1x 10(11) CN706 particles prevented LNCaP xenograft tumor progression, but antitumor activity was eliminated by a pre-existent 1:80 NAb titer. These results led us to propose transient removal of pre-existent adenovirus antibody by immunoapheresis. An affinity column of cloned virus capsid proteins was constructed that was able to specifically remove adenovirus antibody from human clinical serum samples. A 5-min disposable immunoassay was also developed to monitor the level of pre-existent antibody in sera before and after immunoapheresis. Clinically, this approach may enable controlled clinical studies of intravenously administered adenovirus in patients with pre-existent anti-adenovirus antibody.

Adenoviruses, Human↗

PubMed2000

Properties of packable dental composites.

The introduction of many new packable composites suggests that these products are rapidly gaining popularity. The purpose of this study was to evaluate the in vitro properties of a variety of packable composites and to determine if significant enhancements in physical and mechanical properties have been achieved for these materials compared with two popular nonpackable posterior composites. For the five packable and two regular composites tested (ALERT, Pyramid-Dentin, Pyramid-Enamel, Solitaire, SureFil, Heliomolar, and Z100), the values for fracture toughness, flexure strength, flexure modulus, hardness, and volumetric polymerization shrinkage were determined. In general, although the packable composites were of heavier consistency, they had mechanical properties that were intermediate to (ALERT, Pyramid, and SureFil) or lower than (Solitaire) those of the nonpackable materials. These results could have been predicted based on the similar methacrylate resin chemistry and filler volumes of the various composites. No composite had adequate depth-of-cure when tested in increments greater than 2 mm thick. Polymerization contraction of the packable composites was similar to or higher than that of the nonpackable composites. In addition, the radiopacity of at least one material, Solitaire, was not considered to be adequate (less than 2 mm of aluminum). The results of this study suggest that these packable composites are unlikely to offer improved clinical performance over well-placed nonpackable composites.

Acrylic Resins↗

PubMed1998

High incidence and prevalence of multiple sclerosis in south east Scotland: evidence of a genetic predisposition.

OBJECTIVE: To determine the incidence and prevalence of multiple sclerosis in the Lothian and Border Health Board Regions of south east Scotland. METHODS: Incidence study: all patients were identified in whom a diagnosis of Poser category probable or definite multiple sclerosis was made by a neurologist between 1992 and 1995. Prevalence study: all patients known to have multiple sclerosis who were alive and resident in the study area on 15 March 1995 were recorded. RESULTS: The crude annual incidence rates of probable or definite multiple sclerosis per 100000 population were the highest ever reported: 12.2 (95% confidence interval (95% CI) 10.8-13.7) in the Lothian Region and 10.1 (95% CI 6.6-13.6) in the Border Region. A total of 1613 patients with multiple sclerosis were resident in the study area, giving standardised prevalence rates per 100000 population of 203 (95% CI 192-214) in the Lothian Region and 219 (95% CI 191-251) in the Border Region. Prevalent cases were more likely than expected to have a Scottish surname (risk ratio 1.24, 95% CI 1.14-1.34). CONCLUSION: Orkney and Shetland were previously thought to have by far the highest prevalence of multiple sclerosis in the world: about double that found in England and Wales. However, the prevalence in south east Scotland is equally high, suggesting that the Scottish population as a whole has a genetic susceptibility to the disease, and undermining the hypothesis that patterns of infection specific to small sparsely populated island communities are important in the causation of multiple sclerosis.

Adolescent↗

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↗

PubMed1991

Optical biosensor assay (OBA).

We describe a new biosensor immunoassay involving optical diffraction to detect clinically important analytes in human body fluids. A silicon wafer is used as a support for immobilization of antigen or antibody. The protein-coated surface is illuminated through a photo mask to create distinct periodic areas of active and inactive protein. When the surface is incubated with a positive sample, antigen-antibody binding occurs only on the active areas. Upon illumination with a light source such as a laser, the resulting biological diffraction grating diffracts the light. A negative sample does not result in diffraction because no antigen-antibody binding occurs to create the diffraction grating. The presence or absence of a diffraction signal differentiates between positive and negative samples, and the intensity of the signal provides a quantitative measure of the analyte concentration. The technique is demonstrated with a quantitative assay of choriogonadotropin in serum.

Biosensing Techniques↗

PubMed1991

[Ambulatory vigil anesthesia for implant surgery].

The length of certain implant surgery operation as well as their precision requires the complete cooperation of patients. The vigilambulant anesthesia, regularly used in other medical specialties, ensures in total security, anxiolism, sedation, analgesia and amnesia for patients. The presence of an anesthesist having at his disposal all the material and all drugs for anesthesia and reanimation gives the surgeon an unequalled operatory comfort.

Alfentanil↗

PubMed1983

Oral levonantradol in the control of cancer chemotherapy-induced emesis.

A dose-ranging study with oral levonantradol was performed in 20 cancer patients. The optimum oral dose which attenuated vomiting accompanying chemotherapy was 1 mg 4-hourly. Side-effects comprised dizziness, confusion, euphoria, drowsiness, and difficulty in concentrating. There was no cardiovascular toxicity. Overall toxicity appeared to be dose-related and was mild and acceptable.

Antiemetics↗

PubMed1983

A randomised multicentre single blind comparison of a cannabinoid anti-emetic (levonantradol) with chlorpromazine in patients receiving their first cytotoxic chemotherapy.

One hundred and eight patients selected to receive combinations of highly emetic cytotoxic chemotherapy for malignant disease were included in a study of anti-emetic therapy. The patients were randomly allocated to receive levonantradol (0.5, 0.75 or 1 mg) or chlorpromazine (25 mg) prior to receiving their first course of cytotoxic therapy. The appropriate anti-emetic was administered 2 hr prior to the start of chemotherapy, 2 hr after chemotherapy and subsequently at 4-hourly intervals for a further 8 hr. The extent of anorexia, nausea and vomiting along with other side-effects were assessed at regular intervals by physicians and nursing staff during the 24 hr following chemotherapy. In addition, a self-assessment questionnaire was completed by the patients. Levonantradol (0.5 mg) was superior to chlorpromazine (25 mg) as an anti-emetic. Both were reasonably well tolerated, although at this dose of levonantradol 22% of patients experienced dysphoric reactions. At higher doses of levonantradol the proportion of patients experiencing these reactions rose to 50%, but without a concomitant increase in antiemetic activity. Neither drug achieved satisfactory control of vomiting in patients receiving combinations containing cis-platinum. We conclude that levonantradol (0.5 mg) is a more effective anti-emetic than chlorpromazine (25 mg) in patients receiving cytotoxic chemotherapy. However, its use cannot be recommended due to its high incidence of unacceptable central nervous system side-effects.

Adolescent↗

PubMed1977

Immunoglobulin class-specific antibody response in serum, spleen, lungs, and bronchoalveolar washings after primary and secondary sendai virus infection of germfree mice.

Immunoglobulin class-specific antibodies were measured by a solid-phase radioimmunoassay in serum, bronchoalveolar washings (BAW), lung cell lysates, and spleen cell lysates in germfree mice after intranasal (i.n.) and intraperitoneal (i.p.) primary and secondary 10(5), 10(4), and 10(3) mean tissue culture infective doses (TCID(50)) of live parainfluenza 1 (Sendai) virus. The earliest antibody detected in lungs after i.n. virus challenge was immunoglobulin G (IgG), followed by IgM and, lastly, IgA. The local IgA response after both primary and secondary i.n. virus challenge was lowest after the severest infection. It is suggested that the delayed appearance of IgA antibody and the lower response after severe lung damage may be related to a temporary local secretory component-producing cell deficiency. The lungs were a major source of serum IgG antibody after both primary and secondary i.n. virus challenge. Only IgG and IgM antibodies were detectable in lung cell lysates after the i.n. 10(3) TCID(50) secondary response. A secondary response was detected in IgG, IgA, and IgM after secondary i.n. challenge with the other two doses. The lung response to all of primary and secondary i.p. doses of virus was exclusively IgG and IgM. Calculation of radioimmunoassay antibody per microgram of IgG, IgA, and IgM in serum and BAW after both i.n. and i.p. virus challenges showed that, when BAW antibody was present, the ratio in BAW was always higher than that in serum. This finding in the i.n. mice, together with the presence of IgA antibody-containing cells in the lungs, strongly indicates local manufacture and secretion of IgA antibodies in these animals and suggests that the same conclusion could apply to local IgG and IgM antibodies after both i.n. and i.p. challenges.

Animals↗

PubMed1977

Studies of pulmonary and renal immunopathology after nonlethal primary sendai viral infection in normal and cyclophosphamide-treated hamsters.

Hamsters were infected by aerosol with a nonlethal strain of Sendai virus. The virus infected mainly bronchial mucosal cells, some alveolar cells, and occasional renal tubular cells. By the third day after infection, there was an impressive local influx of inflammatory and IgG-secreting cells at sites of infection, disruption and desquamation of infected mucosal cells, and destruction of bronchial basement membrane. These findings were associated with the presence of specific antibodies bound to viral antigens in the tissues. Treatment with cyclophosphamide resulted in the ablation of these histologic events, failure to eradicate virus or to produce antibody, and some spontaneous deaths. Viral antigens were regularly detected in kidneys on days 3, 6, and 9 as a fine, granular glomerular and tubular basement membrane staining pattern after elution of tissue sections. The IgG deposition was found in a similar pattern at the same times, persisted after Sendai antigens could no longer be detected, and tended toward linear staining, fading with time. Treatment with cyclophosphamide decreased significantly, but did not completely abolish, the renal abnormalities. It was concluded that the humoral immune response is associated with eradication of virus, excess local tissue damage, and some immunopathologic consequences in the kidney.

Animals↗

PubMed1975

A solid phase micro-radioimmunoassay to detect minute amounts of Ig class specific anti-viral antibody in a mouse model system.

A simple and rapid micro-radioimmunoassay was developed to detect and quantitate class specific mouse anti-Sendai virus antibodies. Two different 125I-labelled indicator systems were studied. After incubation of test serum with antigen one system used 125I-rabbit anti-mouse IgG (RIA 1) and the second employed rabbit anti-mouse IgG, IgA or IgM followed by 125I-sheep anti-rabbit immunoglobulin reagent (RIA 2). The RIA 2 method was adopted for routine use as it was more sensitive, gave better discrimination between sample and background counts and eliminated the need for several labelled rabbit anti-mouse Ig class specific antisera. The technique was found to be about 100 times more sensitive than conventional HI tests, specific, reliable and economical of reagents and time.

Animals↗