Biomedical subjects
Publications and source records attributed to E Rogers.
For some groups of species, extinction rates are orders of magnitude higher than expected background rates--many species now last nearer a fateful second than their destined hour.
The work described in this article presents an approach to the integration of computer-displayed radiological images with cooperative computerized assistance for decision-making. The VIA-RAD system (Visual Interaction Assistant for Radiology) is a blackboard-based architecture, founded on extensive data collection and analysis in the domain of diagnostic radiology, together with cognitive modeling of the interaction between perception and problem-solving. The details of this system are presented in terms of domain knowledge representation and domain knowledge mapping. A small prototype of the system has been implemented and tested with radiology subjects, and the results of this study are also described.
Bladder substitution using pouches designed from detubularized bowel is gaining widespread acceptance among urologists and their patients. However, few clinical reports have described the effectiveness of the orthotopic neobladder fashioned from ileum in the manner described by Studer. Since 1988, we have used the Studer technique with minor modifications in 20 men who underwent radical cystoprostatectomy for transitional cell carcinoma of the bladder. Early morbidity from the procedure was minimal, although 2 patients later had anastomotic strictures. Significant late complications included low vitamin B12 levels in 4 patients and persistent hyperchloremia in 1. A total of 18 patients achieved diurnal continence but 9 of these had enuresis. Neobladder compliance and emptying were satisfactory in the 12 patients evaluated urodynamically. Upper tracts remained stable in all patients at a median followup of 24 months (range 9 to 60). Isolated episodes of bacteriuria occurred in 11 patients but followup urine cultures have remained sterile in all continent patients. The Studer ileal neobladder is a simple, effective alternative for urine storage, upper tract preservation and efficient voiding.
We reviewed our experience with salvage radical prostatectomy for locally recurrent cancer in 40 patients to assess the current complication rate and the results using prostate specific antigen (PSA) as an indicator of treatment outcome and to identify better criteria for the selection of appropriate candidates for this operation. Most recurrent cancers were detected by digital rectal examination (26 patients) or increasing serum PSA levels (10). The operation was technically challenging, with 6 rectal injuries (15%), 2 requiring temporary colostomy. Serious technical complications were more common (31%) among the 29 patients who underwent pelvic lymphadenectomy at the time of initial radiotherapy than among the 11 treated with external irradiation alone (9%). Urinary incontinence persisted in 18 of 31 evaluable patients (58%) and was successfully corrected with an artificial urinary sphincter in 9. A total of 21 patients (54%) had pathologically advanced disease (seminal vesicle invasion and/or lymph node metastases). Preoperative PSA levels but not clinical stage or biopsy grade correlated with pathological stage (p < 0.03). If the PSA was less than 10 ng./ml. only 15% of the patients had an advanced pathological stage, compared to 86% if the PSA was 10 or more. After 2 to 97 months (mean 39) 2 patients died of metastatic prostatic cancer, 5 had distant metastases and none had symptomatic local recurrence. At 5 years the actuarial nonprogression rate measured by PSA was 55 +/- 20%. The only pretreatment factor predictive of progression was the serum PSA level. If the PSA was less than 10 ng./ml. the actuarial rate of progression was significantly lower than if the PSA was greater than 10 (p < 0.05). The best results were in the subset of 18 patients with cancer confined to the prostate or immediate periprostatic tissue: 82% had no progression at 5 years. Within each of these pathological stages the results of salvage prostatectomy were similar to those for standard radical prostatectomy in patients with no prior irradiation. Although technically challenging, salvage prostatectomy provides excellent control of radio-recurrent cancer confined to the prostate or immediate periprostatic tissue and is best performed before the preoperative PSA level increases to greater than 10 to 20 ng./ml.
BACKGROUND: We have shown previously that primary prostate cancer demonstrates significant extracellular accumulation of transforming growth factor-beta 1 (TGF-beta 1). To further investigate the potential role of TGF-beta 1 in prostate cancer progression, we evaluated an expanded series of primary prostatic carcinomas and associated lymph node metastases. EXPERIMENTAL DESIGN: Prostate tissue samples from 37 patients were examined. Three were organ donors, all less than 30 years of age, whose prostates were included as normal controls. Eighteen had undergone radical prostatectomy and pelvic lymph node dissection. Eleven were without evidence of metastasis, whereas seven were found to have prostate cancer within at least one of their pelvic lymph nodes. Sixteen had undergone transurethral resection of the prostate for benign disease, yet all had prostate cancer within the resected specimen (15 were stage T1b; 1 was stage T1a). Twelve of the patients with stage T1b disease underwent pelvic lymph node dissection and implantation of radioactive gold seeds. All 12 had prostate cancer in at least one lymph node. All specimens were examined for the level of expression and localization of TGF-beta 1 by immunohistochemistry using Ab that distinguish intracellular from extracellular TGF-beta 1. RESULTS: Normal prostate tissue and benign prostatic hyperplasia demonstrated negative or weak intracellular and extracellular staining for TGF-beta 1. By comparison, 29 of 34 primary prostate cancers showed extensive extracellular TGF-beta 1 staining with pronounced intracellular accumulation within epithelial cells in 13 of 34 patients. There was no difference in the staining pattern for extracellular TGF-beta 1 between primary cancers with and without pelvic lymph node metastases. However, in primary cancers without pelvic lymph node metastases, only 1 of 15 patients showed strong intracellular staining for TGF-beta 1 compared with 12 of 19 primary tumors with metastatic disease. In addition, only 2 of 19 lymph node metastases demonstrated weak extracellular TGF-beta 1 staining, but all 19 contained intracellular TGF-beta 1. CONCLUSIONS: These findings confirm our previous observation that prostate cancer exhibits enhanced intracellular and extracellular accumulation of TGF-beta 1 relative to normal prostate tissue and benign prostatic hyperplasia. In addition, our study documented a significantly more pronounced accumulation of intracellular TGF-beta 1 in primary prostate cancer with metastasis than in primary tumors without metastasis. Moreover, although the pattern of intracellular TGF-beta 1 staining observed in the primary tumor is maintained in the metastasis, a lack of extracellular accumulation of TGF-beta 1 in the metastatic site was noted. This differential pattern may be biologically important and could conceivably reflect a role for TGF-beta 1 in disease progression.
Carcinoma of the prostate is the commonest malignancy of the genitourinary tract in the male and is frequently associated with metastatic bone disease. Serial isotope bone scans for screening secondary deposits are not cost-effective. We have evaluated the serum prostate markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) as an alternative to conventional serial bone scanning in 129 patients with newly diagnosed prostate cancer over a period of 3 years. Although serum PSA did not reflect local tumour burden at presentation, it was significantly elevated in those who presented with stage D disease (p < 0.01). 45 patients presented de novo with metastatic bone deposits and a further 18 patients developed metastases during the study period. The sensitivity of PSA in detecting secondary deposits at presentation for levels in excess of 100 micrograms/l was 93.75%, the positive predictive value 95.7% and the negative predictive value for levels less than 5 micrograms/l was 90.6%. During the follow-up period the sensitivity was 94.4%, the positive predictive value 100% and the negative predictive value 100%, with a median lead time of 3 months in predicting metastases in the 18 patients with progressive disease. When compared with PAP, PSA was found to be a statistically superior marker of bone metastases both at presentation and follow-up (p < 0.05). We recommend that PAP measurements are no longer necessary and should be replaced by PSA, and that serial serum PSA estimations should determine the need for future isotope bone scans in the patient with established prostate cancer.
This study examined the relationship between mothers and their teenage daughters in order to determine if there was a significant difference in perceived relationships between pregnant and nonpregnant mother-daughter dyads in a predominantly black sample. Results indicated that the nonpregnant daughters and their mothers felt significantly more intimacy toward each other than did the pregnant daughters and their mothers. However, correlations of the mother and daughter scores revealed that the intimacy scores of the mothers of the pregnant daughters were positively correlated with their daughters' attachment scores, suggesting that the mothers and their pregnant daughters were more in agreement regarding their relationship than were the nonpregnant mother-daughter pairs.
Investigations directed toward the development of an effective artificial blood substitute are continuing as concerns remain regarding the safety and adequacy of the nation's blood supply. Perfluorochemical compounds, modified hemoglobin solutions, and microencapsulated hemoglobin represent the major areas of research. If a successful red cell substitute can be developed, many problems inherent in current blood transfusion practices could be alleviated, particularly in emergency situations.
In vitro refolding after urea unfolding of the enzyme rhodanese (thiosulfate:cyanide sulfurtransferase, EC 2.8.1.1) normally requires the assistance of detergents or chaperonin proteins. No efficient, unassisted, reversible unfolding/folding transition has been demonstrated to date. The detergents or the chaperonin proteins have been proposed to stabilize folding intermediates that kinetically limit folding by aggregating. Based on this hypothesis, we have investigated a number of experimental conditions and have developed a protocol for refolding, without assistants, that gives evidence of a reversible unfolding transition and leads to greater than 80% recovery of native enzyme. In addition to low protein concentration (10 micrograms/ml), low temperatures are required to maximize refolding. Otherwise optimal conditions give less than 10% refolding at 37 degrees C, whereas at 10 degrees C the recovery approaches 80%. The unfolding/refolding phases of the transition curves are most similar in the region of the transition, and refolding yields are significantly reduced when unfolded rhodanese is diluted to low urea concentrations, rather than to concentrations near the transition region. This is consistent with the formation of "sticky" intermediates that can remain soluble close to the transition region. Apparently, nonnative structures, e.g. aggregates, can form rapidly at low denaturant concentrations, and their subsequent conversion to the native structure is slow.
In vitro refolding of the monomeric mitochondrial enzyme, rhodanese (thiosulfate sulfurtransferase; EC 2.8.1.1) is facilitated by molecular chaperonins. The four components: two proteins from Escherichia coli, chaperonin 60 (groEL) and chaperonin 10 (groES), MgATP, and K+, are necessary for the in vitro folding of rhodanese. These were previously shown to be necessary for the in vitro folding of ribulose-1,5-bisphosphate carboxylase at temperatures in excess of 25 degrees C (Viitanen, P. V., Lubben, T. H., Reed, J., Goloubinoff, P., O'Keefe, D. P., and Lorimer, G. H. (1990) Biochemistry 29, 5665-5671). The labile folding intermediate, rhodanese-I, which rapidly aggregates at 37 degrees C in the absence of the chaperonins, can be stabilized by forming a binary complex with chaperonin 60. The discharge of the binary chaperonin 60-rhodanese-I complex, results in the formation of active rhodanese, and requires the presence of chaperonin 10. Optimal refolding is associated with a K(+)-dependent hydrolysis of ATP. At lower protein concentrations and 25 degrees C, where aggregation is reduced, a fraction of the rhodanese refolds to an active form in the absence of the chaperonins. This spontaneous refolding can be arrested by chaperonin 60. There is some refolding (approximately equal to 20%) when ATP is replaced by nonhydrolyzable analogs, but there is no refolding in the presence of ADP or AMP. ATP analogs may interfere with the interaction of rhodanese-I with the chaperonins. Nondenaturing detergents facilitate rhodanese refolding by interacting with exposed hydrophobic surfaces of folding intermediates and thereby prevent aggregation (Tandon, S., and Horowitz, P. (1986) J. Biol. Chem. 261, 15615-15618). The chaperonin proteins appear to play a similar role in as much as they can replace the detergents. Consistent with this view, chaperonin 60, but not chaperonin 10, binds 2-3 molecules of the hydrophobic fluorescent reporter, 1,1'-bi(4-anilino)naphthalene-S,5'-disulfonic acid, indicating the presence of hydrophobic surfaces on chaperonin 60. The number of bound probe molecules is reduced to 1-2 molecules when chaperonin 10 and MgATP are added. The results support a model in which chaperonins facilitate folding, at least in part, by interacting with partly folded intermediates, thus preventing the interactions of hydrophobic surfaces that lead to aggregation.
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A smoking attitude survey was developed and administered to adolescent patients, parents, and staff members at a psychiatric hospital for adolescents 6 months before and 6 months after the institution of a patient smoking ban. Attitudes before the ban were significantly more favorable toward allowing patient smoking than attitudes after the ban; smokers were significantly more in favor of allowing patient smoking than nonsmokers; and patients were significantly more in favor of allowing patient smoking than parents, who were significantly more in favor of allowing patient smoking than staff (overall ps less than 0.0001; post-hoc ps less than 0.05). The findings support the feasibility of implementing smoking bans in adolescent inpatient facilities.
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The DNA adduct O4-ethylthymine can be alkylated under mild conditions with pentafluorobenzyl bromide. The product has good gas chromatographic characteristics and also forms a structurally characteristic anion in high yield when subjected to electron capture mass spectrometry. Related adducts for other DNA bases behave similarly. These properties stimulated us to develop a general analytical method based on the derivatization reaction. Important for this method is an oxidation-elimination reaction that mildly releases a base from a nucleoside. Thus, a general analytical method based on pentafluorobenzylation is now available for determining many alkyl and related DNA adducts.
Between 1 September 1980 and 31 August 1983, 352 patients with inactive or mildly active Crohn's disease but not taking drug treatment apart from sulphasalazine were entered from 40 hospitals into a prospective trial to assess the effects of two different diets on disease activity over two years. One hundred and sixty two patients were randomly allocated to take a diet unrestricted in sugar and low in fibre and 190 to a diet with little or no sugar and high in unrefined carbohydrate. No clear difference in clinical course was detected among patients who accepted the two different types of dietary advice.
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Although anthracycline antibiotics are among the most useful chemotherapy agents, the risk of producing cardiomyopathy and the absence of a reliable noninvasive technique to predict subclinical cardiomyopathy remain a major problem. We retrospectively reviewed our experience with anthracyclines over a 5-year period. Cardiomyopathy developed in 6 of 112 patients (5.3%) treated with anthracyclines and was fatal in 5 of the 6 patients. Our incidence and mortality rates are higher than those previously reported.
Dietary surveys have shown that patients with Crohn's disease tend to eat more sucrose than control subjects and this investigation was undertaken to determine whether a diet rich in refined carbohydrate affects the bacterial flora of the terminal ileum. Ileostomy effluent in five patients with Crohn's disease and five with ulcerative colitis after two weeks on a diet rich in sucrose and refined cereal has been compared with the same period on a diet low in sucrose and rich in unrefined cereal. Observations were made hourly for nine hours after equicaloric breakfasts representing the two diets. The amount of ileostomy effluent was greater on the unrefined carbohydrate diet both in terms of wet weight (238 +/- 89 g vs 162 +/- 79 g, p less than 0.02) and dry weight (23 X 6 +/- 6.8 g vs 14.9 +/- 6.6 g, p less than 0.01); surprisingly, the amount of glucose and oligosaccharide was also greater (169 +/- 41 mg vs 82 +/- 26 mg, p less than 0.001) in all 10 volunteers. The bacteriological flora per gram was also higher on the unrefined carbohydrate diet after the test meal (p less than 0.02 between three and six hours) as a result of a general increase in all organisms. The relative proportions of the organisms did not vary between the two diets. No differences were detected between patients with ulcerative colitis and those with Crohn's disease.