Biomedical subjects
R Atkinson
Publications and source records attributed to R Atkinson.
Bioassay-directed fractionation of mutagenic PAH atmospheric photooxidation products and ambient particulate extracts.
Simulated atmospheric gas-phase reactions of naphthalene, fluorene and phenanthrene have been carried out in an environmental chamber with bioassay-directed chemical analysis of the reaction products. Nitro-PAH were found to be the most significant mutagens formed from the reactions of naphthalene and fluorene. The mutagram (bar graph of mutagenic activity versus HPLC fraction) of the phenanthrene reaction products closely resembled that of an ambient air particulate extract with the most mutagenic activity being in a fraction more polar than that in which the nitro-PAH elute. Nitrophenanthrene lactones (nitro-6H-dibenzo[b,d]pyran-6-ones) were found to account for the observed activity of this polar fraction of the phenanthrene reaction products. It has been shown that the utilization of an environmental chamber with a known PAH-starting material and the ability to produce sufficient product for isomer-specific identifications of mutagens is a promising complement to bioassay-directed fractionation of ambient air particulate extracts.
A randomised study comparing standard dose carboplatin with chlorambucil and carboplatin in advanced ovarian cancer.
A total of 161 previously untreated patients with FIGO stage III or IV epithelial ovarian cancer were randomised after surgery to receive six courses of either carboplatin 400 mg m-2 alone (Arm A) or carboplatin 300 mg m-2 with chlorambucil 10 mg day-1 for 7 days (Arm B). The median progression free survival (PFS) was similar: arm A: 45 weeks; arm B: 61 weeks (P = 0.830). Multivariate Cox regression analysis showed that the extent of residual disease and performance status were the most important prognostic factors for PFS. Fifty-two per cent of patients received dose escalations based on nadir blood counts, and 89% of all dose adjustments were made according to protocol. Failure to achieve a significant degree of leucopenia was associated with worse progression free survival (P less than 0.001). A total of 29.4% of patients fall into this category. The median survival was similar in both arms, i.e. 75 weeks. It is unlikely that there is any major clinical advantage to adding chlorambucil to single agent carboplatin for the management of advanced ovarian cancer, but whether used in combination or a single agent, the dose of carboplatin should be sufficient to cause at least grade I leucopenia. This may best be achieved by determining the initial dose based on renal function, and then adjusting subsequent doses according to nadir blood counts.
Early loss of heterozygosity on 17q in ovarian cancer. The Abe Ovarian Cancer Genetics Group.
We have studied 146 ovarian tumours (94 carcinomas, 22 tumours of low malignant potential and 30 benign tumours) for evidence of allele loss on chromosome 17p and 17q sufficient to imply the proximity of a tumour-suppressor gene. We have examined two polymorphic loci (YNZ22.2 and BHP53) on 17p13 and one on chromosome 17q (17q23-qter). Loss of heterozygosity (LOH) was detected in 34/63 (54%) informative malignant tumours at YNZ22.2 and 22/47 (47%) at BHP53; on 17q, 45/64 (70%) had LOH. Allele loss was detected in a small number of benign and borderline tumours. There was a statistically significant difference between the patterns of allele loss in serous and endometrioid groups of tumours, and allele loss occurred with significantly greater frequency on 17q than on 17p. Comparison of all malignant tumours presenting with either localized (FIGO stage I/II) or widespread (FIGO stage III/IV) disease showed that, particularly on 17q, allele loss increases in the more advanced stages. The p53 tumour-suppressor gene is implicated in ovarian carcinogenesis, and our findings suggest that an important tumour-suppressor gene may be located in the region 17q23-qter. Loss of function in this gene may be responsible for the frequently observed rapid progression of serous-type adenocarcinomas to an advanced stage.
Incessant ovulation and ovarian cancer.
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Atmospheric lifetimes of dibenzo-p-dioxins and dibenzofurans.
The experimental and theoretical data available concerning the gas- and particle-phase reactions of polychlorodibenzo-p-dioxins (PCDDs) and polychlorodibenzofurans (PCDFs) are discussed. These data lead to the expectation that the dominant tropospheric loss processes of gas-phase PCDDs and PCDFs will be photolysis and reaction with the OH radical, with the OH radical reaction being the most important for the less chlorinated species. The estimated tropospheric lifetimes of gas-phase PCDFs increase significantly more rapidly with the degree of chlorination than is the case for PCDDs. For particle-associated PCDDs and PCDFs, the dominant tropospheric removal processes are expected to be photolysis and wet and dry deposition, with wet and dry deposition of the host particles being the most important. The estimated lifetimes in the lower troposphere range from less than 1 day for dibenzo-p-dioxin, the mono-, di- and trichlorodibenzo-p-dioxins, dibenzofuran and the monochlorodibenzofurans present in the gas phase, to greater than or equal to 10 days for particle-associated PCDDs and PCDFs, with a general increase in the tropospheric lifetime with the degree of chlorination. While long-range transport of PCDDs is expected to occur for those PCDDs which are totally or mainly particle associated, gas- and particle-phase PCDFs containing four or more chlorine atoms are also expected to have sufficiently long tropospheric lifetimes to undergo long-range transport.
Normality and adolescence.
Diagnostic work with adolescents has always been difficult. The problem is to distinguish serious psychopathology from mild crisis. We can now say, however, that a severe identity crisis and emotional turmoil are just not part of normal growing up. Our belief is that we do not help adolescents who experience such crises or turmoil when we tell them not to worry about their problems because they are a normal part of adolescence and because they will "grow out of it." In summary, we have presented data on the self-image of a large number of adolescents. We have stressed three things. First, we used self-administered questionnaires to collect our data. Most important, our data are consistent, and they are congruent with results obtained from use of other psychologic instruments such as interviews or parents' evaluations of their children. Second, we found that the normal groups of adolescents we studied were characterized more by their similarities than by their differences. The continuity of values for all our samples over an 18-year period and across cultures was especially impressive. Third, we stressed the diversity of adolescents' view of their psychologic worlds. These youths define normal functioning and development. They reside in our communities, and before we can help their disturbed peers who need professional help, we need to know what the norm is. Only then can we correctly diagnose and successfully treat the adolescents who do seek our help.
Early complications of knee-joint arthroscopy.
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Cervical cancer deaths in young women.
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Elective cross-hand transfer: a case report with a five-year follow-up.
The elective free microvascular cross-hand transfer of the right hand to the left distal carpus was successfully performed in a 35-year old professional photographer. Traumatic loss of the left hand with preservation of a useful thumb and concomitant right upper extremity injury leaving the right hand with an amputated thumb, but paralyzed and insensate from a brachial plexus palsy 5 years before transfer, set the stage for such a reconstruction. Multiple immediate tendon transfers and primary nerve grafting provided for finger flexion and extension plus functional sensibility in this first reported case of an elective cross-hand microvascular transfer. Five years follow-up demonstrates useful and powerful flexion, and functional extension of digits in the reconstructed left hand and right upper extremity function has been improved with a below-elbow prosthesis.
The contribution of nitrofluoranthenes and nitropyrenes to the mutagenic activity of ambient particulate organic matter collected in southern California.
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The development of purpose in adolescence: insights from the narrative approach.
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Neurofibromatosis xenografts. Contribution to pathogenesis.
We transplanted Schwann cells of 3 patients with neurofibromatosis from neurofibromas, sural nerve, and from a malignant schwannoma into sciatic nerves of immunoincompetent mice. Three and six months later, the grafts and distal nerve segments contained normal myelinated fibers. After rendering host animals immune competent again, neurofibroma and malignant schwannoma Schwann cells were rejected, but grafts retained normally myelinated fibers indicating that these were of mouse origin. Sural nerve Schwann cells from a neurofibromatosis patient were rejected also leaving naked axons in the grafted segments showing that human Schwann cells from the sural nerve of one patient had invested and myelinated the regenerating mouse axons. The nature of putative signals passing between axons and Schwann cells might be elucidated by the combination of human and animal cells in immunoincompetent host nerves. Hypothetical signals for myelination of mouse axons were normally received by sural nerve Schwann cells of a patient with neurofibromatosis, but not by Schwann cells from neurofibromas or malignant schwannomas.
Perception of orientation of motion as affected by change in divergence of texture, change in size, and in velocity.
When there is relative motion between an observer and a textured surface such as the ground, motion-related visual information is available about the orientation of the surface through vergence of the paths of the elements of the texture, change in their sizes and in their velocities. This experiment determined the perceptual effectiveness of each variable in foveal and peripheral viewing for producing perceptions of three-dimensional motion. The three variables were electronically separated and displayed singly, in all possible pairs, and all together. Subjects communicated their perceptions of degree of perceived surface tilt at the top, bottom, and middle of the display for the eight different combinations of variables because, during pilot work perceived surface bendings were frequently noted where top, bottom, and middle appeared tilted to different extents. All three variables can lead to relatively reliable perceptions of perceived orientation of the plane of motion, with change in velocity being the most powerful determiner. Change in size was the weakest. Certain combinations can lead to perceptions of extreme warping and should be avoided in motion displays. Subjects consistently underestimate the amount of simulated tilt. Foveal viewing was more accurate than peripheral viewing but peripheral performance was adequately consistent as an input channel for some orientation tasks.
Traumatic arteriovenous fistula of the thumb after blunt trauma: a case report.
Arteriovenous malformations in the hand are uncommon and traumatic arteriovenous fistulas that result from hand-penetrating injuries are rare. We report a case of traumatic arteriovenous fistula of the thumb subsequent to blunt trauma.
Generalized paroxysmal fast activity: electroencephalographic and clinical features.
We reviewed electroencephalographic and clinical features of 20 patients with generalized paroxysmal fast activity (GPFA). All had seizure disorders and all but 3 had more than one seizure type. Mental retardation was present in 17 patients. In most cases no cause for the seizures could be found. GPFA occurred almost exclusively in sleep. Fifteen patients had clinical seizures associated with this activity; in 8 the seizures were tonic. Additional generalized epileptiform abnormalities were present in 18 patients, 10 of whom had slow spike and wave complexes. Only 4 patients had normal background activity.