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Biomedical subjects

D E Thompson

Publications and source records attributed to D E Thompson.

At least 37 records · Page 2Linked to original sources

A virtual five-link model of the thumb.

Most researchers have modelled the thumb as three rigid links with connections of two universal joints (carpometacarpal joint and metacarpo-phalangeal joint), and a hinge joint (interphalangeal joint). Although this produces the required number of degrees of freedom, the resulting motion is not anatomically accurate. In this work, the thumb is modelled as a five-link manipulator with the virtual links connected by hinge joints-one for each degree of freedom of the thumb. The axes of the hinges are not orthogonal to one another, in the long axis of the bones or to the anatomic planes. Four static positions of hand function were analysed-key pinch, screwdriver hold, tip pinch, and wide grasp. The virtual five-link model of the thumb predicted similar muscle recruitment patterns to published EMG data. The force at the distal surface of the trapezium is between 6 and 24 times the applied load depending on the posture.

Biomechanical Phenomena↗

A prospective study of rectal methohexital: efficacy and side effects in 648 cases.

Rectal methohexital has been used for nearly 30 yr in pediatric anesthesia. Despite this long and increasingly varied use, no large prospective series has been published detailing safety and efficacy. This study prospectively evaluated the efficacy, safety, and side effects of this medication in a series of 648 cases. On 553 of 648 occasions (85%), the child fell asleep after a single 30-mg/kg dose of 10% methohexital. Sleep was less likely in patients with myelomeningocele or who were receiving oral phenobarbital or phenytoin. When sleep occurred, the average time to onset of sleep was 6 min. Most patients who remained awake 15 min after drug were sedated. Defecation (10%) and hiccups (13%) were common but benign side effects. Partial airway obstruction and/or desaturation to Spo2 < or = 93% occurred in 26 patients (4%), but was resolved with blow-by oxygen and/or jaw-thrust in all but two cases. These two patients (0.3% of total) required aggressive airway intervention by the supervising anesthesiologist. Apnea did not occur in any patient. Methohexital has a high efficacy rate for sleep (85%) or sedation (96%), and has a relatively rapid onset. Significant respiratory side effects occur infrequently, but can be life threatening if not properly managed.

Administration, Rectal↗

Nucleotide sequence of the gene coding for non-proteolytic Clostridium botulinum type B neurotoxin: comparison with other clostridial neurotoxins.

The neurotoxin gene of non-proteolytic Clostridium botulinum type B (strain Eklund 17B) was cloned as a series of overlapping polymerase chain reaction (PCR) fragments generated with primers designed to conserved regions of published botulinal toxin (BoNT) sequences. The 3' end of the gene was obtained by using primers designed to the determined sequence of non-proteolytic BoNT/B and a published downstream region of BoNT/B gene from a proteolytic strain. Translation of the nucleotide sequence derived from cloned PCR fragments demonstrated the toxin gene encodes a protein of 1291 amino acid residues. Comparative alignment of the derived BoNT/B sequence with those of other published botulinal neurotoxins revealed highest sequence relatedness with BoNT/B of proteolytic C. botulinum. The sequence identity between non-proteolytic and proteolytic BoNT/B was 97.7% for the light chain (corresponding to 10 amino acid changes) and 90.2% for the heavy chain (corresponding to 81 amino acid changes), with most differences occurring at the C-terminal end. A genealogical tree constructed from all known botulinal neurotoxin sequences revealed marked topological differences with a phylogenetic tree of C. botulinum types based upon small-subunit (16S) ribosomal RNA sequences.

Amino Acid Sequence↗

Cancer incidence in atomic bomb survivors. Part I: Use of the tumor registries in Hiroshima and Nagasaki for incidence studies.

More than 30 years ago, population-based tumor registries were established in Hiroshima and Nagasaki. This report, the first of a series of papers on cancer incidence, describes methodological aspects of the tumor registries and discusses issues of data quality in the context of the Life Span Study (LSS) cohort, the major atomic bomb survivor population. The tumor registries in Hiroshima and Nagasaki are characterized by active case ascertainment based on abstraction of medical records at area hospitals, augmented by tissue registries operational in the area and a number of clinical and pathological programs undertaken over the years among the atomic bomb survivors. Using conventional measures of quality, the Hiroshima and Nagasaki tumor registries have a death certificate-only (DCO) rate of less than 9%, a mortality/incidence (M/I) ratio of about 50%, and a histological verification (HV) rate in excess of 70%, which place these registries among the best in Japan and comparable to many established registries worldwide. All tumor registry data pertaining to the LSS population were assembled, reviewed and handled with special attention given to the quality and uniformity of data based on standardized procedures. Special studies and monitoring programs were also introduced to evaluate the quality of the tumor incidence data in the LSS. Analyses were performed to examine the quality of incidence data overall and across various substrata used for risk assessment such as age, time and radiation dose groups. No significant associations were found between radiation dose and data quality as measured by various indices. These findings warrant the use of the present tumor registry-based data for studies of cancer incidence in the atomic bomb survivors.

Adolescent↗

Cancer incidence in atomic bomb survivors. Part II: Solid tumors, 1958-1987.

This report presents, for the first time, comprehensive data on the incidence of solid cancer and risk estimates for A-bomb survivors in the extended Life Span Study (LSS-E85) cohort. Among 79,972 individuals, 8613 first primary solid cancers were diagnosed between 1958 and 1987. As part of the standard registration process of the Hiroshima and Nagasaki tumor registries, cancer cases occurring among members of the LSS-E85 cohort were identified using a computer linkage system supplemented by manual searches. Special efforts were made to ensure complete case ascertainment, data quality and data consistency in the two cities. For all sites combined, 75% of the cancers were verified histologically, 6% were diagnosed by direct observation, 8% were based on a clinical diagnosis, and 12.6% were ascertained by death certificate only. A standard set of analyses was carried out for each of the organs and organ systems considered. Depending on the cancer site, Dosimetry System 1986 (DS86) organ or kerma doses were used for computing risk estimates. Analyses were based on a general excess relative risk model (the background rate times one plus the excess relative risk). Analyses carried out for each site involved fitting the background model with no dose effect, a linear dose-response model with no effect modifiers, a linear-quadratic dose-response model with no effect modifiers, and a series of linear dose-response models that included each of the covariates (sex, age at exposure, time since exposure, attained age and city) individually as effect modifiers. Because the tumor registries ascertain cancers in the registry catchment areas only, an adjustment was made for the effects of migration. In agreement with prior LSS findings, a statistically significant excess risk for all solid cancers was demonstrated [excess relative risk at 1 Sv (ERR1Sv) = 0.63; excess absolute risk (EAR) per 10(4) person-year sievert (PY Sv) = 29.7]. For cancers of the stomach (ERR1SV = 0.32), colon (ERR1SV = 0.72), lung (ERR1SV = 0.95), breast (ERR1SV = 1.59), ovary (ERR1SV = 0.99), urinary bladder (ERR1SV = 1.02) and thyroid (ERR1SV = 1.15), significant radiation associations were observed. There was some indication of an increase in tumors of the neural tissue (excluding the brain) among persons exposed to the bombs before age 20. For the first time, radiation has been associated with liver (ERR1SV = 0.49) and nonmelanoma skin (ERR1SV = 1.0) cancer incidence in the LSS cohort. The present analysis also strengthened earlier findings, based on a smaller number of cases, of an effect of A-bomb radiation on salivary gland cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Cancer incidence in atomic bomb survivors. Part IV: Comparison of cancer incidence and mortality.

This report compares cancer incidence and mortality among atomic bomb survivors in the Radiation Effects Research Foundation Life Span Study (LSS) cohort. Because the incidence data are derived from the Hiroshima and Nagasaki tumor registries, case ascertainment is limited to the time (1958-1987) and geographic restrictions (Hiroshima and Nagasaki) of the registries, whereas mortality data are available from 1950-1987 anywhere in Japan. With these conditions, there were 9,014 first primary incident cancer cases identified among LSS cohort members compared with 7,308 deaths for which cancer was listed as the underlying cause of death on death certificates. When deaths were limited to those occurring between 1958-1987 in Hiroshima or Nagasaki, there were 3,155 more incident cancer cases overall, and 1,262 more cancers of the digestive system. For cancers of the oral cavity and pharynx, skin, breast, female and male genital organs, urinary system and thyroid, the incidence series was at least twice as large as the comparable mortality series. Although the incidence and mortality data are dissimilar in many ways, the overall conclusions regarding which solid cancers provide evidence of a significant dose response generally confirm the mortality findings. When either incidence or mortality data are evaluated, significant excess risks are observed for all solid cancers, stomach, colon, liver (when it is defined as primary liver cancer or liver cancer not otherwise specified on the death certificate), lung, breast, ovary and urinary bladder. No significant radiation effect is seen for cancers of the pharynx, rectum, gallbladder, pancreas, nose, larynx, uterus, prostate or kidney in either series. There is evidence of a significant excess of nonmelanoma skin cancer in the incidence data, but not in the mortality series. Cancers of the salivary gland and thyroid are also in excess in the incidence series, but they were not evaluated in the earlier mortality analyses. For all solid tumors the estimated excess relative risk at 1 Sv (ERR1Sv) for incidence (ERR1Sv = 0.63) is 40% larger than the excess relative risk (ERR) based on mortality data from 1950-1987 in all Japan (ERR1Sv = 0.45). The corresponding excess absolute risk (EAR) point estimate is 2.7 times greater for incidence than mortality. For some cancer sites, the difference in the magnitude of risk between incidence and mortality is greater. These differences reflect the greater diagnostic accuracy of the incidence data and the lack of full representation of radiosensitive but relatively nonfatal cancers, such as breast and thyroid, in the mortality data. Analyses of both incidence and mortality data are needed since the two end points provide complementary information for risk assessment.

Adolescent↗

Nucleotide sequence of the gene coding for Clostridium barati type F neurotoxin: comparison with other clostridial neurotoxins.

The neurotoxin gene from Clostridium barati ATCC43756 was cloned as a series of overlapping polymerase chain reaction (PCR) generated fragments using primers designed to conserve toxin sequences previously published. The toxin gene has an open reading frame (ORF) of 1268 amino acids giving a calculated molecular mass of 141,049 Da. The sequence identity between the C. barati ATCC43756 and non-proteolytic C. botulinum 202F neurotoxins is 64.2% for the light chain and 73.6% for the heavy chain. This is much lower than reported identities for the type E neurotoxins from C. botulinum and C. butyricum (96% identity between light chains and 98.8% between the heavy chains). Previously identified conserved regions in other botulinal neurotoxins were also conserved in that of C. barati. An ORF upstream of the toxin coding region was revealed. This shows strong homology to the 3' end of the gene coding for the nontoxic-nonhemagglutinin (NTNH) component of the progenitor toxin from C. botulinum type C neurotoxin.

Amino Acid Sequence↗

Genetic interrelationships of saccharolytic Clostridium botulinum types B, E and F and related clostridia as revealed by small-subunit rRNA gene sequences.

The phylogenetic interrelationships of saccharolytic C. botulinum types B, E and F together with eleven other saccharolytic clostridia were examined by 16S rRNA gene sequencing. Comparative analysis of the sequence data revealed that the saccharolytic C. botulinum types B, E and F were highly related and represent a single genetic group. Strains of C. barati and C. butyricum that produce botulinal neurotoxin revealed almost 100% 16S rRNA sequence identity with their respective non-toxigenic counterparts and were phylogenetically distinct from saccharolytic C. botulinum (types B, E and F). Proteolytic C. botulinum type F was shown to be phylogenetically remote from the saccharolytic C. botulinum group. The implications of the sequence data for the taxonomy of the C. botulinum complex are discussed.

Base Sequence↗

Poly(2-hydroxyethyl methacrylate) sponges as implant materials: in vivo and in vitro evaluation of cellular invasion.

The pore size and the in vivo behaviour of four poly(2-hydroxyethyl methacrylate) sponges were investigated. The sponges were synthesized by polymerization of monomer in 70, 80 and 90 wt% water, respectively. In one of the formulations, a high amount of initiator was added. The average pore diameter was calculated with Ferry's equation and the results compared to those obtained by examination of samples using environmental scanning electron microscopy. The use of the equation greatly underestimated the size of pores. We also showed that the pores in polymers obtained in 70 wt% water were not interconnected, whilst the pores in polymers obtained in 80 and 90 wt% water, respectively, were larger and interconnected throughout the polymer. When implanted subcutaneously in rabbits, only the latter polymers allowed invasion and proliferation of cells. Penetration and proliferation of cells in these sponges were also assessed by an in vitro method using cultured human fibroblasts. The procedure included the overlaying of a glass plate covered by confluent cultured cells on to the surface of polymer impregnated with collagen. The depth of migration and number of sections needed to be cut to count a fixed number of invading cells were measured after incubation for 2 wk and used as indicators in comparing the ability of various sponges to allow cellular invasion. The assay showed that more cells invaded a hydrogel sponge produced in 80 wt% water than one produced in 90 wt% water. It also showed that the cut polymer surfaces allowed a greater cellular invasion than the moulded ones.

Animals↗

Tissue interaction with hydrogel sponges implanted in the rabbit cornea.

We proposed poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel sponges as potential materials for the peripheral zone of a composite keratoprosthesis. It was previously shown that such sponges allowed cellular invasion when implanted s.c. in rabbits. To evaluate the reaction elicited by these materials in the corneal tissue, a PHEMA sponge, with pore size diameters of 10-30 microns, was produced, impregnated with collagen, and implanted in the rabbit cornea in both central and limbal regions of separate eyes. The eyes were examined by slit-lamp biomicroscopy up to 6 months postoperatively. Enucleation was performed at 3 weeks, 6 weeks, and 6 months, then excised implants were examined by light and transmission electron microscopy. Both clinical and histopathological examination indicated that sponges were well tolerated by the stromal and limbal tissues. No capsule was formed around any of the implants. Corneal fibroblasts and capillaries readily invaded the internal voids in the sponge to all depths. The invading cells remained viable and active up to the end of the follow-up period. Our findings suggest that hydrophilic PHEMA sponges may be successful as peripheral keratoprosthetic materials able to provide a permanent and tight fusion of the keratoprosthesis with the host tissue.

Animals↗

Construction of biological surface models from cross-sections.

An approach improving on existing techniques is presented for blending cross-sections of biological objects to produce a polynomial surface model. As intermediate steps to the final surface skinning, representative data points on the cross-sections are selected for defining piecewise cubic B-splines providing an immediate reduction in storage and computational requirements for the contour representation of the objects. A mesh of quadrilateral patches is subsequently formed over adjacent cross-sections using bicubic B-spline surfaces which exhibit second parametric derivative (C2) continuity. The surface model provides a complete and robust representation with significant data reduction. The resulting algorithm is demonstrated using bone data of a human hand.

Biomechanical Phenomena↗

Studies on the ribosomal RNA operons of Listeria monocytogenes.

A 23S rRNA gene of Listeria monocytogenes was cloned into pUC19 on a 6.2-kb Pst I fragment. Hybridisation studies demonstrated the presence of the 5S and partial 16S rRNA genes within the clone. The nucleotide sequence of the region encoding the 23S rRNA was found to be highly homologous with those of other low G + C Gram-positive bacteria. The 16S-23S intergenic spacer region was amplified using PCR technology and revealed two product sizes, the larger of which contained tRNA(Ala) and tRNA(Ileu) genes. Further tRNA genes were found downstream of the 5S rRNA gene.

Base Sequence↗

Sequence of the gene encoding type F neurotoxin of Clostridium botulinum.

Primers designed to conserved regions of botulinum and tetanus clostridial toxins were used to amplify DNA fragments from non-proteolytic Clostridium botulinum type F (202F) DNA using polymerase chain reaction technology. The fragments were cloned and the complete nucleotide sequence of the gene encoding type F toxin determined. Analysis of the nucleotide sequence demonstrated the presence of an open frame encoding a protein of 1274 amino acids, similar to other botulinum neurotoxins. Upstream of the toxin gene is the end of an open reading frame which encodes the C-terminus of a protein with homology to non-toxic-non-hemagglutinin component of type C progenitor toxin.

Amino Acid Sequence↗

PCR cloning and nucleotide sequence determination of the 18S rRNA genes and internal transcribed spacer 1 of the protozoan parasites Cryptosporidium parvum and Cryptosporidium muris.

The genes encoding 18S rRNA and internal transcribed spacer 1 (1TS1) of Cryptosporidium parvum and Cryptosporidium muris were amplified from oocysts by PCR utilizing primers complementary to conserved regions of the 5' end of 18S and 5.8S rRNA. PCR products were cloned and the complete nucleotide sequences of two clones of each Cryptosporidium species were determined. The 18S rRNA genes of C. parvum and C. muris showed more than 99% sequence identity.

Animals↗

Analysis of operons encoding 23S rRNA of Clostridium botulinum type A.

Southern hybridization analysis of Clostridium botulinum type A chromosomal DNA indicated the presence of six copies of the 23S rRNA gene. Fragments of DNA encoding 23S rRNA were amplified by polymerase chain reaction and cloned in Escherichia coli. Three clones examined by restriction enzyme and sequence analysis were found to be derived from different operons. Sequence determination of the entire insert of two clones revealed nine nucleotide changes in the genes coding for 23S rRNA (99.7% sequence identity) between operons encoded on the same chromosome, showing microheterogeneity in the rRNA operons of this organism.

Base Sequence↗

In vitro cytotoxicity of melanized poly(2-hydroxyethyl methacrylate) hydrogels, a novel class of ocular biomaterials.

Due to their ability to absorb ultraviolet and visible radiation, we have proposed the melanized poly(2-hydroxyethyl methacrylate) hydrogels as biomaterials suitable for the manufacture of soft artificial intraocular lenses. Their biocompatibility has not been evaluated so far. In this study, poly(2-hydroxyethyl methacrylate) containing various amounts of adrenochrome-melanin were synthesized and the cytotoxicity of their aqueous extracts was assessed by using four in vitro testing techniques (trypan blue dye exclusion, inhibition of DNA synthesis, lactate dehydrogenase release, and inhibition of cell growth). Assays were based on incubation with human choroidal fibroblasts. By the first three techniques, no cytotoxicity was found in the extracts. The inhibition of cell growth test showed a slight cellular protein loss, however only in the extracts of polymers with high melanin content. The results suggest that the release of potentially toxic agents from melanized hydrogels into an aqueous medium is not significant. However, when an assay in collagen gel was carried out in the presence of specimens of melanized hydrogels, a toxic reaction was clearly revealed. This can be caused by a delayed release of toxic molecules from melanin, or by some other mechanism. The use of melanin-containing polymers as implant materials becomes questionable and further research is necessary.

Biocompatible Materials↗

Cytotoxic effects of residual chemicals from polymeric biomaterials for artificial soft intraocular lenses.

Development of improved hydrogels for soft intraocular lenses, based on 2-hydroxyethyl methacrylate monomer, requires the use of various other monomers and polymerization additives which have potential ocular toxicity. Three monomers, 2-hydroxyethyl methacrylate, methyl methacrylate, and 2-ethoxyethyl methacrylate, as well as two common inhibitors, hydroquinone and 4-methoxyphenol, were subjected to in vitro cytotoxicity assays as aqueous solutions at different concentrations. A new polymerization initiator, 2,2'-azo-bis-(2,4-dimethyl valeronitrile), was thermally decomposed in water at different concentrations and the products were also assayed for cytotoxicity. Assays were based on incubation with human choroidal fibroblasts. Cell death was evaluated by trypan blue dye exclusion, DNA synthesis inhibition, and lactate dehydrogenase tests. While methyl methacrylate and 2-ethoxyethyl methacrylate were found nontoxic, the other chemicals displayed high cytotoxicity. However, when extracts of synthesized poly(2-hydroxyethyl methacrylate) specimens, differentially treated after polymerization, were subjected to the same assays it was found that toxicity from residual 2-hydroxyethyl methacrylate monomer was lost during steam sterilization and storage in water because of the removal of the monomer through aqueous washing. The lack of toxicity in these specimens suggests that residual contents of inhibitor and initiator are too low to cause toxic effects on choroidal fibroblasts. It is concluded that hydrogels have low cytotoxic effects in vitro.

Anisoles↗