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Biomedical subjects

E J Adams

Publications and source records attributed to E J Adams.

At least 37 records · Page 2Linked to original sources

Optimization of stereotactically-guided conformal treatment planning of sellar and parasellar tumors, based on normal brain dose volume histograms.

PURPOSE: To investigate the optimal treatment plan for stereotactically-guided conformal radiotherapy (SCRT) of sellar and parasellar lesions, with respect to sparing normal brain tissue, in the context of routine treatment delivery, based on dose volume histogram analysis. METHODS AND MATERIALS: Computed tomography (CT) data sets for 8 patients with sellar- and parasellar-based tumors (6 pituitary adenomas and 2 meningiomas) have been used in this study. Treatment plans were prepared for 3-coplanar and 3-, 4-, 6-, and 30-noncoplanar-field arrangements to obtain 95% isodose coverage of the planning target volume (PTV) for each plan. Conformal shaping was achieved by customized blocks generated with the beams eye view (BEV) facility. Dose volume histograms (DVH) were calculated for the normal brain (excluding the PTV), and comparisons made for normal tissue sparing for all treatment plans at > or =80%, > or =60%, and > or =40% of the prescribed dose. RESULTS: The mean volume of normal brain receiving > or =80% and > or =60% of the prescribed dose decreased by 22.3% (range 14.8-35.1%, standard deviation sigma = 7.5%) and 47.6% (range 25.8-69.1%, sigma = 13.2%), respectively, with a 4-field noncoplanar technique when compared with a conventional 3-field coplanar technique. Adding 2 further fields, from 4-noncoplanar to 6-noncoplanar fields reduced the mean normal brain volume receiving > or =80% of the prescribed dose by a further 4.1% (range -6.5-11.8%, sigma = 6.4%), and the volume receiving > or =60% by 3.3% (range -5.5-12.2%, sigma = 5.4%), neither of which were statistically significant. Each case must be considered individually however, as a wide range is seen in the volume spared when increasing the number of fields from 4 to 6. Comparing the 4- and 6-field noncoplanar techniques to a 30-field conformal field approach (simulating a dynamic arc plan) revealed near-equivalent normal tissue sparing. CONCLUSION: Four to six widely spaced, fixed-conformal fields provide the optimum class solution for the treatment of sellar and parasellar lesions, both in terms of normal brain tissue sparing and providing a relatively straightforward patient setup. Increasing the number of fields did not result in further significant sparing, with no clear benefit from techniques approaching dynamic conformal radiotherapy in the cases examined.

Brain↗

Comparison of intensity-modulated tomotherapy with stereotactically guided conformal radiotherapy for brain tumors.

PURPOSE: Intensity-modulated radiotherapy (IMRT) offers the potential to more closely conform dose distributions to the target, and spare organs at risk (OAR). Its clinical value is still being defined. The present study aims to compare IMRT with stereotactically guided conformal radiotherapy (SCRT) for patients with medium size convex-shaped brain tumors. METHODS AND MATERIALS: Five patients planned with SCRT were replanned with the IMRT-tomotherapy method using the Peacock system (Nomos Corporation). The planning target volume (PTV) and relevant OAR were assessed, and compared relative to SCRT plans using dose statistics, dose-volume histograms (DVH), and the Radiation Therapy Oncology Group (RTOG) stereotactic radiosurgery criteria. RESULTS: The median and mean PTV were 78 cm3 and 85 cm3 respectively (range 62-119 cm3). The differences in PTV doses for the whole group (Peacock-SCRT +/-1 SD) were 2%+/-1.8 (minimum PTV), and 0.1%+/-1.9 (maximum PTV). The PTV homogeneity achieved by Peacock was 12.1%+/-1.7 compared to 13.9%+/-1.3 with SCRT. Using RTOG guidelines, Peacock plans provided acceptable PTV coverage for all 5/5 plans compared to minor coverage deviations in 4/5 SCRT plans; acceptable homogeneity index for both plans (Peacock = 1.1 vs. SCRT = 1.2); and comparable conformity index (1.4 each). As a consequence of the transaxial method of arc delivery, the optic nerves received mean and maximum doses that were 11.1 to 11.6%, and 10.3 to 15.2% higher respectively with Peacock plan. The maximum optic lens, and brainstem dose were 3.1 to 4.8% higher, and 0.6% lower respectively with Peacock plan. However, all doses remained below the tolerance threshold (5 Gy for lens, and 50 Gy for optic nerves) and were clinically acceptable. CONCLUSIONS: The Peacock method provided improved PTV coverage, albeit small, in this group of convex tumors. Although the OAR doses were higher using the Peacock plans, all doses remained within the clinically defined threshold and were clinically acceptable. Further improvements may be expected using other methods of IMRT planning that do not limit the treatment delivery to transaxial arcs. Each IMRT system needs to be individually assessed as the paradigm utilized may provide different outcomes.

Algorithms↗

Evidence for an HLA-C-like locus in the orangutan Pongo pygmaeus.

HLA-B and C are related class I genes which are believed to have arisen by duplication of a common ancestor. Previous study showed the presence of orthologues for both HLA-B and C in African apes but only for HLA-B in Asian apes. These observations suggested that the primate C locus evolved subsequent to the divergence of the Pongidae and Hominidae. From an analysis of orangutan Tengku two HLA-C-like alleles (Popy C*0101 and Popy C*0201) were defined as well as three HLA-B-like (Popy-B) alleles. By contrast, no Popy-C alleles were obtained from orangutan Hati, although three Popy-B alleles were defined. Thus an HLA-C-like locus exists in the orangutan (as well as a duplicated B locus), implying that the primate C locus evolved prior to the divergence of the Pongidae and Hominidae and is at least 12-13 million years old. Uncertain is whether all orangutan MHC haplotypes contain a C locus, as the failure to find C alleles in some individuals could be due to a mispairing of HLA-C-specific primers with certain Popy-C alleles. These results raise the possibilities that other primate species have a C locus and that the regulation of natural killer cells by C allotypes evolved earlier in primate evolution than has been thought.

Alleles↗

Comparison of a multi-leaf collimator with conformal blocks for the delivery of stereotactically guided conformal radiotherapy.

Stereotactically-guided conformal radiotherapy is a practical technique for irradiating irregular lesions in the brain. The shaping of the conformal fields may be achieved using lead alloy blocks, a conventional multi-leaf collimator (MLC) or a mini/micro-MLC. Although the former gives more precise shaping, it is labour intensive. The latter methods are more practical as both mould room and treatment room times are reduced, but the shaping is limited by the finite leaf-width. This study compares treatment plans, in terms of normal tissue doses and tumour coverage, for fields shaped using conformal blocks and a conventional MLC in two series of geometrical shapes and nine patient tumours. For the range of tumour sizes considered (volumes 14-264 cm3, minimum dimension 30 mm, maximum 102 mm), the MLC treats, on average, 14% (range 3-34%) and 17% (range 0-36%) more normal brain tissue than conformal blocks to >50% and >80% of the prescription dose, respectively. The large variability is due to strong dependence on tumour shape and the presence of partial leaf-widths in the MLC fit. It is therefore important to consider both of these effects when deciding whether the MLC is appropriate for a particular target volume.

Brain Neoplasms↗

Demographic characteristics in adult paternity for first births to adolescents under 15 years of age.

PURPOSE: To examine parental demographic characteristics by adult (> or = 20 years at baby's conception) and teenage (< 20 years at baby's conception) paternity in births to very young adolescents (< 15 years at baby's conception). METHODS: This was a population-based, retrospective cohort analysis of all 12,317 very young adolescent mothers residing in California with a first singleton live birth during 1993-1995. Risks for adult, compared to teenage, paternity were evaluated using multivariate logistic regression. RESULTS: Adult fathers, responsible for 26.7% of births to very young adolescents, were a mean of 8.8 years older than the mother. The risk factors for adult compared to adolescent paternity were as follows: father's educational attainment of at least 3 years below that considered adequate for his age [adjusted odds ratio (AOR) = 8.34], father's (AOR = 2.46) or mother's (AOR = 1.36) educational attainment 1-2 years below that considered adequate for their age, mother's birthplace outside the United States (AOR = 3.12), and father's Hispanic ethnicity (AOR = 1.60) or African-American race (AOR = 1.50). CONCLUSIONS: Adult fathers were responsible for over one quarter of the births in our study. Adolescent pregnancy prevention focusing on younger adolescents must programmatically address adult paternity. Variations in adult paternity patterns across cultural groups suggest that we need further study of the role that cultural beliefs and practices play in very young adolescent pregnancy.

Adolescent↗

Analysis of a successful immune response against hepatitis C virus.

To investigate the type of immunity responsible for resolution of hepatitis C virus (HCV) infection, we monitored antibody and intrahepatic cytotoxic T lymphocyte (CTL) responses during acute (<20 weeks) infection in chimpanzees. Two animals who terminated infection made strong CTL but poor antibody responses. In both resolvers, CTL targeted at least six viral regions. In contrast, animals developing chronic hepatitis generated weaker acute CTL responses. Extensive analysis of the fine specificity of the CTL in one resolver revealed nine peptide epitopes and restriction by all six MHC class I allotypes. Every specificity shown during acute hepatitis persisted in normal liver tissue more than 1 yr after resolution. These results suggest that CD8+CTL are better correlated with protection against HCV infection than antibodies.

Acute Disease↗

Comparison of different scoring systems for immunohistochemical staining.

AIM: To carry out an objective assessment of two systems of scoring immunohistochemical staining, evaluating interobserver and intraobserver error. METHODS: 92 cervical tumours underwent immunohistochemical staining for p53 and epidermal growth factor receptor. Staining was assessed using two methods: a standard 4 point scale and a descriptive method, performed by three observers. Interobserver and intraobserver error were assessed for both scoring methods. RESULTS: In terms of interobserver error between three observers, no difference was found between a simple 4 point scale method of evaluation and the use of a highly circumscribed method. In all evaluations, interobserver error was scored as moderate (kappa w 0.48-0.49). However, evaluation of immunohistochemical staining by a panel of observers led to a marked improvement in the interobserver error scores (kappa w 0.63). CONCLUSIONS: There should be standardisation of immunohistochemical staining and scoring methods. More attention should be paid to measurement of interobserver and intraobserver error in studies. Use of a panel of tissue control slides and consensus scoring by several observers can lead to improvement in reproducibility.

ErbB Receptors↗

A major histocompatibility complex class I allele shared by two species of chimpanzee.

Little is known regarding the rates at which natural selection can modify or retain antigen presenting alleles at the major histocompatibility complex (MHC). Discovery of identical [1101 base pairs (bp)] coding regions at the MHC class I C locus in Pan troglodytes and Pan paniscus, chimpanzee species that diverged approximately 2.3 million years ago, now indicates that a class I allotype can survive for at least this period. Remarkable conservation was also reflected in the (1799 bp) introns where a maximum of only six substitutions distinguished five alleles (three from P. troglodytes and two from P. paniscus) that encoded the identical heavy chain allotype. Analysis of a more distantly related human allele, HLA-Cw*0702, corroborated that intron variation was non-uniform along the gene. Thus we provide a clear reference frame for the lifetime of an MHC class I allotype, a direct estimate of allelic substitution rates, and evidence for an unusual evolution of MHC class I introns.

Alleles↗

Characteristics of children having multiple Medicaid-paid asthma hospitalizations.

OBJECTIVES: We undertook this population-based study to describe the characteristics of poor children with multiple asthma hospitalizations and to discern if poor minority children have a greater risk for these events than poor white children. METHODS: We conducted a retrospective analysis of 1994 California hospital discharge data for asthma hospitalizations among 1 to 12-year-old Medicaid patients (N = 6844 discharges). Risk factors for multiple Medicaid asthma hospitalizations were calculated by using logistic regression procedures. RESULTS: In 1994, asthma hospitalizations accounted for 11.6% of Medicaid-funded hospitalizations for 1 to 12-year-olds in California. These hospitalizations had a mean length of 2.7 days and a mean hospital charge of $6532. After we controlled for source of admission and length of stay, African American children (OR, 1.93; 95% CI 1.49-2.49) and Latino children (OR, 1.34; 95% CI 1.04-1.72) had a higher risk of multiple Medicaid-paid hospitalizations for asthma than did white children. Adjusted odds ratios for multiple asthma hospitalizations were 1.35 (CI, 1.05-1.74) for children with emergency room admissions, and 1.16 (CI, 0.97-1.39) for children having hospital stays of at least 5 days duration. CONCLUSIONS: Among children with Medicaid-paid hospitalizations for asthma, the risk for multiple asthma hospitalizations within a year was greater among African Americans and Latinos than among whites. Programs attempting to decrease repeat hospitalizations for asthma may benefit by focusing on these populations.

Black or African American↗

CK-1, a putative chemokine of rainbow trout (Oncorhynchus mykiss).

Chemokines are small inducible proteins that direct the migration of leukocytes. While chemokines are well characterised in mammals, they have yet to be identified in fish. We have isolated a cDNA clone from rainbow trout (Oncorhynchus mykiss) which encodes a protein (CK-1) having structural features typical of chemokines. Amino-acid residues that define the beta-chemokines of mammals are conserved in CK-1, including the paired cysteine motif, CC. Further similarities are shared with the C6 subfamily of beta-chemokines. In contrast, the organisation of the CK-1 gene is closer to that of mammalian alpha-chemokine genes than beta-chemokine genes. The CK-1 gene is present in all four salmonid species examined and the nucleotide sequences of the exons are highly conserved. CK-1 has characteristics in common with mammalian alpha and beta-chemokine genes, suggesting that this salmonid chemokine gene preserves traits once present in the ancestral chemokine gene from which modern mammalian chemokine genes evolved.

Animals↗

Changes in the epidemiologic profile of sudden infant death syndrome as rates decline among California infants: 1990-1995.

OBJECTIVES: To evaluate changes in the rates and epidemiologic patterns of sudden infant death syndrome (SIDS) after implementation of public health campaigns to promote back sleeping and reduce exposure to cigarette smoke and environmental risk factors for SIDS. METHODS: California vital statistics data were used to evaluate changes in SIDS rates (deaths/1000 live births) and in the proportions of SIDS deaths by age and season of occurrence for California infants of black or other races from 1990 through 1995. RESULTS: From 1990 through 1995, 3508 SIDS deaths occurred. SIDS rates declined from 2.69 to 2.15 for black infants and from 1.04 to 0.61 for others between 1990 and 1995. Most SIDS deaths occurred during the 2nd to 4th months of life; the proportion of SIDS deaths during this period was unchanged for blacks but decreased for others from 70% to 65%. Of all SIDS deaths, 62% occurred during the colder season (October through March); the proportion of deaths in each season did not change for either race. CONCLUSION: California SIDS rates declined 20% for blacks and 41% for others between 1990 and 1995. Declines coincided with campaigns to reduce environmental risk factors for SIDS. Blacks continue to be at increased risk for SIDS compared with others, and the SIDS rate for blacks relative to others has increased. Reductions in SIDS mortality coinciding with interventions were smaller for blacks than for others. New strategies are needed to reduce further SIDS rates and narrow the gap between blacks and others.

Black or African American↗

The earlier the better: an evaluation of changes to teaching Year 1 nuclear medicine.

OBJECTIVE: In 1996 changes were made to the nuclear medicine content and mode of delivery in the Year 1 degree program at The University of Sydney, Australia. The aim was to evaluate whether changes made to the program raised the clinical abilities of students entering their clinical placement in Year 2. METHODS: Questionnaires to assess the students' perception of how well Year 1 had prepared them for their clinical Year 2 were distributed to both the 1995 and 1996 students. The clinical supervisors also were surveyed to determine if the 1996 students demonstrated any difference in their understanding and application of nuclear medicine technology principles. RESULTS: The 1996 students were more positive about their clinical readiness and the clinical supervisors observed an increased level of understanding and application by the 1996 students. CONCLUSION: Changes in the Year 1 curriculum provided students with a higher level of clinical readiness at the commencement of their Year 2 clinical placement.

Australia↗

Natural inactivation of a common HLA allele (A*2402) has occurred on at least three separate occasions.

HLA-A*2402 is common and widely distributed in human populations. Several individuals were identified who type genotypically for A*2402, but are serologically null for the HLA-A24 Ag. Sequencing and transfection of genomic DNA fragments containing null and wild-type A*2402 alleles, and the related A*2301 allele, revealed three different null alleles (A*2409N, A*2411N, and A*2402(low)), each of which differs from A*2402 by a single nucleotide change within the 6.7-kb sequence. The A*2301 and A*2402 sequences differ by no substitutions additional to those previously determined for the 1.1-kb cDNA. In exon 4, A*2409N has an in-frame stop codon, while A*2411N has a nucleotide insertion that alters the reading frame, causing premature termination. A*2402(low) has a nucleotide substitution near the splice acceptor site for intron 2 that impairs the production of correctly spliced mRNA. For A*2409N and A*2411N, mRNA is undetectable by Northern analysis, whereas A*2402(low) produces a low level of mRNA and a concomitant amount of normal A*2402 protein at the cell surface. The protein expressed from the A*2402(low) allele is sufficient to stimulate an alloreactive T cell response. On a background of unexpected sequence homogeneity, the single nucleotide changes in the A*2409N, A*2411, and A*2402(low) alleles have dramatic effects upon gene expression and are of likely importance for HLA matching in clinical transplantation. Segregation of at least three independently inactivated A*2402 alleles in human populations raises the possibility that loss of A*2402 may be the result of natural selection.

Alleles↗

HLA class I genotyping by cDNA sequence of a Vietnamese family expressing a weak B46 antigen.

Serological heterogeneity in HLA-B46 antigens has been described. Previous studies have identified B*4601 as the allele encoding the "strong" B46 antigen found in Chinese populations. Serological characterization of a Vietnamese family revealed a "weak" B46 antigen. Complementary DNA for the HLA-A, B and C alleles of three family members were cloned and the coding regions sequenced. The allele encoding the weak B46 antigen has the same coding sequence as B*4601, demonstrating that the antigenic differences are not due to polymorphism in the amino acid sequence of the HLA-B heavy chain. The recently described HLA-B*1525 and HLA-Cw*0403 alleles were also found to segregate in this Vietnamese family.

Alleles↗

Episodic evolution and turnover of HLA-B in the indigenous human populations of the Americas.

Nucleotide sequences were determined for the HLA-A, B and C alleles of three populations of Amerindians: the Havasupai tribe from North America, and the Guarani and Kaingang tribes from South America. All 15 Havasupai alleles are found in Eastern Hemisphere populations, whereas the Guarani and Kaingang each have six alleles that appear to be present only in the Western Hemisphere. Nine of the "new" alleles come from HLA-B, one comes from HLA-A and one from HLA-C: ten appear to be the result of recombination and one the result of point substitution. Of the 14 Guarani alleles and 16 Kaingang alleles, only four are held in common. Despite their differences, the three tribes possess comparable numbers of HLA class I alleles, revealing a trend for "allele turnover", in which new alleles tends to supplant older alleles rather than supplement them. Although many new HLA-B alleles have been produced in Latin America, their net effect has been to differentiate populations, not to increase allele diversity within a population. From sequence comparisons, the Amerindian subset of HLA class I allotypes appears to cover the overall ranges of peptide binding specificity, natural killer-cell interactions, and CD8 interactions, that are found in all HLA class I. The recombinations that produced the new alleles of the Kaingang and Guarani class I are predicted to have modulated these functional properties rather than radically change them. Exchange of Bw4 and Bw6 motifs by recombination are noticeably absent in the events forming new alleles in America, whereas they have been the most common of recombinations elsewhere.

Alleles↗

Estimation of fetal and effective dose for CT examinations.

Doses from CT examinations are difficult to estimate. However, they are requested more frequently due to the increase in CT examinations. In particular, fetal dose estimations are frequently required for patients who have discovered, subsequent to the examination, that they were pregnant when the examination was conducted. A computer model has been developed to facilitate such dose calculations. This model combines empirical beam data with anatomical information. The model has been verified using thermoluminescent dosemeter (TLD) readings of internal and surface dose from both phantoms and patients, including intrauterine doses for patients undergoing afterloading gynaecological intracavitary treatment. Although only limited experimental data were available, the results indicate that the model accurately predicts uterine doses within acceptable errors. This approach has been validated for fetal dose estimation. The model was also used in a comparison with the nationally available CT dose data from the National Radiological Protection Board (NRPB). The two models were found to be in agreement for fetal dose estimations.

Computer Simulation↗