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W Ellis

Publications and source records attributed to W Ellis.

At least 19 recordsLinked to original sources

Utility of clinical criteria in differentiating frontotemporal lobar degeneration (FTLD) from AD.

OBJECTIVE: To assess the ability of the current diagnostic criteria for frontotemporal lobar degeneration (FTLD) to differentiate FTLD from AD. METHODS: Thirty cases with autopsy-proven FTLD and 30 cases of AD, matched for Mini-Mental State Examination score, were identified from the clinical databases of three dementia subspecialty centers, and their charts were reviewed for the presence of clinical features described in the current criteria for FTLD. The proportion of patients with each clinical feature at the first clinical presentation was compared across groups. RESULTS: A significantly larger proportion of patients with FTLD showed behavioral abnormalities, particularly social and personal conduct disorders and emotional blunting, than patients with AD. Few differences in language features were seen between the groups, and many of the language features detailed in the criteria were found in only a small proportion of patients. In both groups, many patients showed neuropsychological abnormalities, except for perceptual difficulties, which were present in many patients with AD but only in a few patients with FTLD. Extrapyramidal motor symptoms were more likely to be present in FTLD. Logistic regression revealed that five features-social conduct disorders, hyperorality, akinesia, absence of amnesia, and the absence of a perceptual disorder-correctly classified 93% of patients with FTLD and 97% of patients with AD. CONCLUSION: A combination of behavioral, neuropsychological, and physical findings is most useful in distinguishing FTLD from AD. Future studies should be directed at establishing more objective methods of identifying these clinical features.

Aged↗

Patient reported complications after prostate brachytherapy.

PURPOSE: Prostate brachytherapy has gained popularity due partly to the low rates of short-term complications shown in studies from highly select clinical practices. These series rely on medical records generated by the treating physician and are prone to underreport complications. We summarize the complication reports obtained directly from patients to establish a more realistic incidence of treatment related problems. MATERIALS AND METHODS: In 1997, 160 consecutive patients treated with prostate brachytherapy at the University of Washington were studied. A questionnaire was designed to determine the rate of complications occurring within 1 year of the procedure. The questions were formulated for ease of use and conciseness, while accounting for easily recalled events associated with complications. A total of 147 (92%) patients completed the questionnaire. RESULTS: There were 8 (5%) patients who required hospital admission for an average of 2 days (range 1 to 7) as a result of the procedure. A total of 56 (38%) patients required nonroutine visits with a physician in an office setting or at an emergency room. Radiation proctitis diagnosed by endoscopy developed in 8 (5%) patients but no one needed surgical intervention. A total of 47 (32%) patients required urinary catheterization at some point after implantation. CONCLUSIONS: We demonstrated a higher rate of short-term complications than those previously reported. Fortunately, the majority of side effects were self-limited and no treatment related mortality or cardiovascular morbidity was seen. Our findings may provide a more realistic account of the complications likely to occur after implantation than might be surmised from previous reports.

Adult↗

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Journal Article↗

Transperineal brachytherapy in patients with large prostate glands.

The purpose of this study is to help clarify the use of prostate size as a selection factor for prostate brachytherapy. From 1997 to 1998, 33 patients with a TRUS-based prostate volume greater than 50 cc were treated at the University of Washington by I-125 (144 Gy) or Pd-103 (115 Gy) implantation for prostatic carcinoma. These 33 patients comprised 7% of the total implants performed. Each patient underwent a preimplant TRUS study in the lithotomy position, taking serial axial images of the prostate at 0.5 cm intervals from the base of the gland to the apex. The contours on the preimplant TRUS images were used to calculate the prostate volumes reported here. Only one patient received supplemental external beam irradiation prior to implantation. Twelve patients were treated with neoadjuvant androgen ablation prior to implantation. The prostate volumes quoted here are those taken after hormonal downsizing. Postimplant axial CT images were digitized to calculate the CT-based target coverage. Preimplant urinary obstructive symptoms were quantified by the criteria of the American Urologic Association. Each patient was contacted at the time of this article preparation to update postimplant morbidity information. In all cases, at least 80% of the postimplant volume was covered, despite a median implant-related volume increase of 15%. Five of the 33 patients' postimplant CT scans showed some degree of incomplete target coverage of the anterior/lateral prostate margin. There was no clear association between inadequate anterior/lateral coverage and the degree of interference. Twelve of the 33 patients developed acute postimplant urinary retention, all occurring within 24 hr of implantation. Within this group of 33 patients with a large prostate volume, there was no relationship between the likelihood of acute or chronic urinary retention and preimplant prostate size or obstructive symptoms. Patients who developed postimplant retention lasting more than one week were generally managed by intermittent self-catheterization. By one month, 85% of patients were catheter-free. Based on the data reported here, we are more inclined to accept patients with a large prostate for implantation without insisting on preimplant size reduction. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 199-205 (2000).

Brachytherapy↗

Prostate brachytherapy in patients with median lobe hyperplasia.

Our aim was to document the technical and clinical course of prostate brachytherapy patients with radiographic evidence of median lobe hyperplasia (MLH). Eight patients with MLH were identified during our routine brachytherapy practice, representing 9% of the 87 brachytherapy patients treated during a 6-month period. No effort was made to avoid brachytherapy in patients noted to have MLH on diagnostic work-up. Cystoscopic evaluation was not routinely performed. Postimplant axial computed tomographic (CT) images of the prostate were obtained at 0.5 cm intervals. Preimplant urinary obstructive symptoms were quantified by the criteria of the American Urologic Association (AUA). Each patient was contacted during the writing of this report to update postimplant morbidity information. There was no apparent association between the degree of MLH and preimplant prostate volume or AUA score. Intraoperatively, we were able to visualize MLH by transrectal ultrasound and did not notice any particular difficulty placing sources in the MLH tissue or migration of sources out of the tissue. The prescription isodose covered from 81% to 99% of the postimplant CT-defined target volume, achieving adequate dose to the median lobe tissue in all patients. Two of the eight patients developed acute, postimplant urinary retention. The first patient required intermittent self-catheterization for 3 months and then resumed spontaneous urination. MLH does not appear to be a strong contraindication to prostate brachytherapy, and prophylactic resection of hypertrophic tissue in such patients is probably not warranted. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 152-156 (2000).

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PART-1: a novel human prostate-specific, androgen-regulated gene that maps to chromosome 5q12.

Genes regulated by androgenic hormones are of critical importance for the normal physiological function of the human prostate gland, and they contribute to the development and progression of prostate carcinoma. We used cDNA microarrays containing 1500 prostate-derived cDNAs to profile transcripts regulated by androgens in prostate cancer cells. This study identified a novel gene that we have designated PART-1 (prostate androgen-regulated transcript 1), which exhibited increased expression upon exposure to androgens in the LNCaP prostate cancer cell line. Northern analysis demonstrated that PART-1 is highly expressed in the prostate gland relative to other normal human tissues and is expressed as different transcripts using at least three different polyadenylation signals. The PART-1 cDNA and putative protein are not significantly homologous to any sequences in the nonredundant public sequence databases. Cloning and analysis of the putative PART-1 promoter region identified a potential binding site for the homeobox gene PBX-la, but no consensus androgen response element or sterol-regulatory element binding sites were identified. We used a radiation hybrid panel and fluorescence in situ hybridization to map the PART-1 gene to chromosome 5q12, a region that has been suggested to harbor a prostate tumor suppressor gene. These results identify a new gene involved in the androgen receptor-regulated gene network of the human prostate that may play a role in the etiology of prostate carcinogenesis.

Amino Acid Sequence↗

Brachytherapy in patients with small prostate glands.

PURPOSE: To better define the role of small prostate volume in selecting patients for brachytherapy. MATERIALS AND METHODS: Thirty patients with a transrectal ultrasound (TRUS)-based prostate volumes less than 20 cc were treated at the University of Washington by permanent isotope implantation for prostatic carcinoma. Preimplant TRUS studies were taken at 0.5-cm intervals from the base of the gland to the apex. Planning margins of 1 to 5 mm were added to the prostatic margins, and sources were routinely planned to be placed as much as 5 mm outside of the prostatic margin. The prescription dose was 144 and 115 Gy for full-dose iodine 125 and palladium 103 monotherapy, respectively. For patients receiving supplemental external-beam irradiation, the implant doses were 120 and 90 Gy for 125I and 103Pd, respectively. The morning following the implant, axial computed tomographic (CT) images of the prostate were obtained at 0.5-cm intervals with patients in the supine position. Follow-up ranged from 11 to 28 months (median 21 months). RESULTS: The median coverage of the postimplant prostate volume by the prescription dose was 92%. To calculate the incidence of source migration, the number of sources placed at the time of implant was compared with the number identified on postimplant CT scan. The median number of sources implanted was 84 (range 65-103) compared to an average of 82 identified postoperatively, which is consistent with a source migration rate of two. A median of 31 sources appeared to be outside of the prostatic margins, as identified on postimplant CT scan (range 14-53). Of the 23 patients contacted at the time of this report, one had developed acute postimplant urinary retention that resolved within 2 weeks of implantation. At last follow-up, patient pre- and postimplant AUA scores were not substantially different, with the median AUA score increasing from 7 (range 2-21) to 8 (range 1-27). CONCLUSIONS: Patients with small prostate volumes appear to have acceptable morbidity and target coverage with prostate brachytherapy. Based on the data reported here, we do not believe that a small prostate volume in itself is a contraindication to brachytherapy.

Brachytherapy↗

Prostate brachytherapy in patients with prior evidence of prostatitis.

PURPOSE: To refute a misconception that a prior history of prostatitis is a contraindication to prostate brachytherapy. METHODS AND MATERIALS: Five patients with clinical or pathologic evidence of prior prostatitis were treated with transperineal brachytherapy. Four of the patients received a single i.v. dose of ciprofloxacin (500 mg) intraoperatively. Postimplant antibiotics were not given. The pretreatment biopsy slides were reviewed. RESULTS: Two of the five patients developed postimplant urinary retention requiring short-term catheterization, and both resolved spontaneously. One patient developed what appeared to be an exacerbation of his chronic prostatitis. CONCLUSION: We continue to recommend prostate brachytherapy for the treatment of clinically organ-confined cancer, with no concern about prior clinical or pathologic evidence of prostatitis.

Aged↗

Use of TRUS to predict pubic arch interference of prostate brachytherapy.

PURPOSE: To demonstrate the potential for transrectal ultrasound (TRUS) to predict pubic arch interference of transperineal needle placement for prostate brachytherapy. METHODS AND MATERIALS: TRUS and pelvic computerized tomography (CT) scans from 22 patients who had transperineal prostate brachytherapy at University of Washington were analyzed for pubic arch visualization and interference. The outer margins of the prostate and the inner margins of the pubic bones from each imaging modality were outlined and compared. RESULTS: The pubic arch was readily visualized by TRUS in 21 of the 22 patients. There was good correlation between TRUS and CT for evaluating the amount of pubic arch interference (r = 0.90). CONCLUSION: TRUS can be substituted for CT imaging to evaluate pubic arch interference of transperineal needle placement for prostate brachytherapy. Eliminating routine CT scanning would reduce the cost of treatment.

Brachytherapy↗

Use of pelvic CT scanning to evaluate pubic arch interference of transperineal prostate brachytherapy.

PURPOSE: To determine the necessity of preoperative evaluation of pubic arch interference in patients with small prostate volumes. METHODS AND MATERIALS: CT scans from 97 consecutive, unselected patients with stage T1 or T2 prostatic carcinoma who had transperineal I-125 or Pd-103 implants at the University of Washington in 1997 were analyzed for pubic arch interference. Transrectal ultrasound (TRUS) was performed with 6.0-MHz transducer with the patient in the lithotomy position and the patient's thighs vertical, similar to that used during the implant procedure. CT scans were obtained with the patient in the supine position, with 0.5-cm images taken at every 0.5 cm. To check for potential arch interference, the largest prostate cross-section was overlaid on the narrowest portion of the pubic arch. The overlap of the pubic arch and the prostate margin is measured at right angles to the inner pubic surface. The prostate volume obtained from the TRUS images was compared with the degree of pubic arch interference in order to determine whether TRUS volume predicted for interference. RESULTS: There was considerable variability in pubic arch interference between patients. The mm of pubic arch overlap with the prostatic margin varied from -11 mm to 20 mm. Patients with larger prostate volumes generally had more pubic arch interference, but the degree of interference was only loosely related to the prostate volume (r = 0.46). CONCLUSIONS: The degree of pubic arch interference is highly variable from one patient to the next and the TRUS volume cannot reliably predict patients who do or do not need a pelvic CT to detect potential arch interference.

Brachytherapy↗

Anticipating prostatic volume changes due to prostate brachytherapy.

The purpose of the study was to determine which clinical parameters might predict individual prostate volume changes from prostate brachytherapy. Fifty consecutive, unselected patients treated at the University of Washington by I-125 or Pd-103 implantation for prostatic carcinoma in 1998 were analyzed. The prostate contours on preimplant transrectal ultrasound (TRUS) images were digitized and the prostate volumes calculated. Postimplant axial CT images of the prostate was obtained at 0.5 cm intervals with patients in the supine position the morning after the implant. The postimplant prostate volume increased by an average factor of 1.7 (+/-0.34) compared with the preimplant volume, the size increase being primarily in the anterior-posterior dimension. The absolute volume change was similar in patients with small vs. large preimplant prostate volume (r = -0.39), but the proportional change was less in patients with a larger prostate volume (r = -0.71). Because patients with a small preimplant prostate had proportionately greater volume increase, their postimplant target coverage was generally less. No single parameter, including preimplant prostate volume, preimplant hormonal deprivation, or supplemental external beam radiation therapy (EBRT) can accurately predict the degree of swelling. The precise significance of and practical solution to implant-related prostate volume changes remains to be determined.

Brachytherapy↗

Phylogeographic differentiation in the mitochondrial control region in the koala, Phascolarctos cinereus (Goldfuss 1817).

The koala, Phascolarctos cinereus, is a geographically widespread species endemic to Australia, with three currently recognized subspecies: P.c. adustus, P.c. cinereus, and P.c. victor. Intraspecific variation in the mitochondrial DNA (mtDNA) control region was examined in over 200 animals from 16 representative populations throughout the species' range. Eighteen different haplotypes were defined in the approximately 860 bp mtDNA control region, as determined by heteroduplex analysis/temperature gradient gel electrophoresis (HDA/TGGE). Any single population typically possessed only one or two haplotypes yielding an average within-population haplotypic diversity of 0.180 +/- 0.003, and nucleotide diversity of 0.16%. Overall, mtDNA control region sequence diversity between populations averaged 0.67%, and ranged from 0% to 1.56%. Nucleotide divergence between populations averaged 0.51%, and ranged from 0% to 1.53%. Neighbour-joining methods revealed limited phylogenetic distinction between geographically distant populations of koalas, and tentative support for a single evolutionarily significant unit (ESU). This is consistent with previous suggestions that the morphological differences formalized by subspecific taxonomy may be interpreted as clinal variation. Significant differentiation in mtDNA-haplotype frequencies between localities suggested that little gene flow currently exists among populations. When combined with microsatellite analysis, which has revealed substantial differentiation among koala populations, we conclude that the appropriate short-term management unit (MU) for koalas is the local population.

Animals↗

Evidence for stabilization of the low-spin state of cytochrome P450 due to shortening of the proximal heme bond.

The cytochrome P450 superfamily of enzymes is ubiquitous, being responsible for the metabolism of a wide range of endogenous and xenobiotic compounds. However, the detailed mechanism of the catalytic cycle of these enzymes is still not fully understood. We describe results, obtained from first principles molecular simulations, which indicate that the low-spin state of the Fe3+ ion, present in the heme moiety at the active site of a cytochrome P450 enzyme, may be stabilized by shortening of the proximal bond of the heme. Calculations indicate that a bond length of less than approximately 2.05 A between the heme Fe3+ ion and the cysteine S, which forms the proximal ligand, would result in the stabilization of the low-spin state of the Fe3+, inhibiting the progress of the P450 catalytic cycle. Our investigation uses novel first principles modeling techniques which treat the entire system quantum-mechanically.

Cytochrome P-450 Enzyme System↗

N-methyl-D-aspartate receptor 1 mRNA distribution in the central nervous system of the weakly electric fish Apteronotus leptorhynchus.

We have isolated a partial cDNA for the N-methyl-D-aspartate (NMDA) receptor 1 (NMDAR1) subunit from an Apteronotus leptorhynchus brain cDNA library. The A. leptorhynchus cDNA fragment, which corresponds to nucleotides 135-903 within the 5' region of the rat NR1 mRNA, encodes 252 amino acids that are >80% identical to the homologous segments of the rat, human, and duck NR1 proteins. RNAse protection assays revealed that the A. leptorhynchus NR1 mRNA was highly enriched in the forebrain and hypothalamus, with lesser amounts in the brainstem, and very low levels in the cerebellum. In situ hybridization also demonstrated that neurons in the pallial forebrain were highly enriched in NR1 transcripts. High levels of NR1 mRNA were found in pyramidal cells within the optic tectum and octavolateral regions. Pyramidal cells of the electrosensory lateral line lobe had the highest levels of expression, and the NR1 mRNA was found to be selectively enriched in their apical dendrites.

Amino Acid Sequence↗