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Biomedical subjects

G Gustafson

Publications and source records attributed to G Gustafson.

At least 37 records · Page 2Linked to original sources

Conformal prostate brachytherapy: initial experience of a phase I/II dose-escalating trial.

PURPOSE: To improve treatment results on prostatic adenocarcinoma, conformal radiation therapy (CRT) has been used. Two major drawbacks of external CRT are: (a) internal organ motion/daily set-up variations, and (b) exclusion of several patients for CRT based on poor geometrical relationships as identified by three dimensional (3D) treatment planning. To overcome the above problems, we began the first prospective Phase I/II dose-escalating clinical trial of conformal brachytherapy (CB) and concurrent external beam irradiation. METHODS AND MATERIALS: Fifty-nine patients with T2b-T3c prostatic adenocarcinoma received 176 transperineal ultrasound-guided conformal high-dose rate (HDR) boost implants. All patients received concomitant external beam pelvic irradiation. Dose escalation of the three HDR-CB fractions proceeded as follows: 5.5 Gy (30 patients), 6 Gy (20 patients), and 6.5 Gy (9 patients). The CB dose was prescribed to the prostate contour as outlined using an online biplanar transrectal ultrasound probe. The urethra, anterior rectal wall, and prostate boundaries were identified individually and outlined at 5 mm intervals from the base to the apex of the gland. The CB using real-time ultrasound guidance with interactive online isodose distributions was performed on an outpatient basis. As needles were placed into the prostate, corrections for prostate displacement were recorded and the isodose distributions were recalculated to represent the new relationship between the needles, prostate, and normal structures. No computerized tomography (CT) planning or implant preplanning was required. RESULTS: No patient was rejected based on poor geometrical relation of pelvic structures. In every implant performed, prostate displacement was noted. Craniocaudal motion of the gland ranged from 0.5-2.0 cm (mean = 1.0 cm), whereas lateral displacement was 0.1-0.4 cm. With the interactive online planning system, organ motion was immediately detected, accounted for, and corrected prior to each HDR treatment. The rectal dose has ranged from 45 to 87%, and the urethral dose from 97 to 112% of the prostate dose. It is significant to note that operator dependence has been completely removed because the interactive online planning system uniformly guides the physicians. CONCLUSIONS: With ultrasound guidance and the interactive online dosimetry system, organ motion (as compared to external beam) is insignificant because it can be corrected during the procedure without increasing target volume margins. Common pitfalls of brachytherapy, including operator dependence and difficulty with reproducibility, have been eliminated with the intraoperative online planning system.

Adenocarcinoma↗

Ultrasound-guided high dose rate conformal brachytherapy boost in prostate cancer: treatment description and preliminary results of a phase I/II clinical trial.

PURPOSE: To improve results for locally advanced prostate cancer, a prospective clinical trial of concurrent external beam irradiation and fractionated iridium-192 (Ir-192) high dose rate (HDR) conformal boost brachytherapy was initiated. METHODS AND MATERIALS: Between November 1991 and February 1994, 99 implants were performed on 33 patients with prostatic adenocarcinoma at William Beaumont Hospital. Using AJCC staging criteria, 9 patients had T2b tumors, 17 patients had T2c tumors, and 7 patients had T3 disease. Patients were treated with (a) 45.6 Gy whole pelvis external irradiation and (b) three HDR fractions of 5.5 Gy each (18 patients) or 6 Gy each (15 patients) to the prostate. Transperineal needle implants using real-time ultrasound guidance with interactive on-line isodose distributions were performed on an outpatient basis during weeks 1, 2, and 3 of external irradiation. Acute toxicity was scored using the Radiation Therapy Oncology Group (RTOG) morbidity grading system. RESULTS: This technique of concurrent external pelvic irradiation and conformal HDR brachytherapy was well tolerated. No significant intraoperative or perioperative complications occurred. Three patients (9%) experienced Grade 3 acute toxicity (two dysuria and one diarrhea). All toxicities were otherwise Grades 1 or 2 and were primarily as expected from pelvic external irradiation. Persistent implant-related toxicities included Grades 1-2 perineal pain (12%) and hematospermia (15%). Median follow-up time was 13 months. Serum prostatic-specific antigen (PSA) levels normalized in 91% of patients (29 out of 32) within 1-14 months (median 2.8 months) after irradiation. PSA levels were progressively decreasing in the other three patients at last measurement. Prospectively planned prostatic rebiopsies done at 18 months in the first 10 patients were negative in 9 out of 10 (90%). CONCLUSIONS: Acute toxicity has been acceptable with this unique approach using conformal high dose rate Ir-192 boost brachytherapy with concurrent external irradiation. The initial tumor response as assessed by serial PSA measurement and rebiopsy is extremely encouraging. Dose escalation will proceed in accordance with the protocol guidelines. Further patient accrual and longer follow-up will allow comparison to other techniques.

Adenocarcinoma↗

A multileaf collimator field prescription preparation system for conventional radiotherapy.

PURPOSE: The purpose of this work is to develop a prescription preparation system for efficient field shaping using a multileaf collimator that can be used in community settings as well as research institutions. The efficiency advantage of the computer-controlled multileaf collimator, over cerrobend blocks, to shape radiation fields has been shown in conformal treatments, which typically require complete volumetric computerized tomographic data for three-dimensional radiation treatment planning--a utility not readily available to the general community. As a result, most patients today are treated with conventional radiation therapy. Therefore, we believe that it is very important to fully use the same efficiency advantage of multileaf collimator as a block replacement in conventional practice. METHODS AND MATERIAL: The multileaf collimator prescription preparation system developed by us acquires prescription images from different sources, including film scanner and radiation treatment planning systems. The multileaf collimator angle and leaf positions are set from the desired field contour defined on the prescription image, by minimizing the area discrepancies. Interactive graphical tools include manual adjustment of collimator angle and leaf positions, and definition of portions of the field edges that require maximal conformation. Data files of the final leaf positions are transferred to the multileaf collimator controller via a dedicated communication link. RESULTS: We have implemented the field prescription preparation system and a network model for integrating the multileaf collimator and other radiotherapy modalities for routine treatments. For routine plan evaluation, isodose contours measured with film in solid water phantom at prescription depth are overlaid on the prescription image. Preliminary study indicates that the efficiency advantage of the MLC over cerrobend blocks in conformal therapy also holds true for conventional treatments. CONCLUSION: Our model of computer-controlled prescription, evaluation, and treatment using multileaf collimators can be effectively implemented in both community settings and research institutions. The resultant increase in treatment efficiency and accuracy is now available for conventional radiotherapy.

Equipment Design↗

High dose rate endobronchial brachytherapy in the management of primary and recurrent bronchogenic malignancies.

BACKGROUND: The clinical, radiographic, and bronchoscopic records of patients treated with out-patient high dose rate (HDR) endobronchial brachytherapy were reviewed to determine its effectiveness in patients with malignant airway obstruction (with or without prior external beam radiation). In addition, quality of life and acute and chronic morbidity were evaluated. METHODS: From January 1, 1989 to June 30, 1993, 46 patients received 128 HDR endobronchial treatments employing a high activity Ir-192 source with a remote afterloader. Patients treated had a total of 22 primary and 17 recurrent bronchogenic carcinomas, 7 of which were metastatic nonpulmonary tumors. Three separate fractions of 7.0 Gy were prescribed to a depth of 1.0 cm. and given 1 week apart. Twelve patients (30%) received prior external beam irradiation (median dose, 58 Gy). RESULTS: Median follow-up for the entire group was 5 months (17.5 for surviving patients). Of the eight asymptomatic patients, five (62%) remained asymptomatic for the remainder of their lives. Of the 38 symptomatic patients, 28 (74%) had significant clinical improvement, and 12 of them remained improved for the duration of their lives. Of thirty-six (78%) patients examined for radiographic response, 25 (69%) had a partial or complete response to this treatment. In patients without prior irradiation, there was a tendency for a higher percentage of clinical and radiographic response. Two patients (4%) experienced mild, transient dysphagia, four patients developed self-limited radiation pneumonitis (9%), and three patients (7%) suffered fatal hemoptysis (all of these patients received prior or concurrent external beam radiotherapy). No factor (i.e., prior radiation therapy, number of catheters placed, surgery, or chemotherapy) predicted an increased risk of complications (P = NS). CONCLUSIONS: Outpatient HDR endobronchial brachytherapy is effective in both preventing and relieving endobronchial obstruction in patients with or without prior irradiation, recurrent lesions, or metastatic nonpulmonary disease. A significant proportion of patients can be rendered asymptomatic for the duration of their lives, hence were provided with improved quality of life. These treatments are well tolerated and safe, and result in minimal long term morbidity.

Aged↗

Outcome and prognostic factors for local recurrence in mammographically detected ductal carcinoma in situ of the breast treated with conservative surgery and radiation therapy.

PURPOSE: We have retrospectively reviewed our institution's experience treating a predominantly mammographically detected population of ductal carcinoma in situ (DCIS) patients with conservative surgery and radiation therapy (CSRT) to determine outcome and prognostic factors for local recurrence. METHODS AND MATERIALS: Between January 1, 1982 and December 31, 1988, 52 consecutive cases of DCIS of the breast were treated with CSRT at William Beaumont Hospital. Forty-six (88%) were mammographically detected nonpalpable lesions. All patients underwent at least an excisional biopsy and 28 (54%) were reexcised. The axilla was surgically staged in 41 (79%) and all were N0. The entire breast was irradiated to 45-50 Gy over 5-6 weeks. The tumor bed was boosted in 49 (94%) so that the minimum dose was 60 Gy. The three patients not boosted received a minimum dose of 50 Gy to the entire breast. Pathologic materials were reviewed by one of the authors. RESULTS: The predominant DCIS pattern was comedo in 40%, cribriform in 28%, solid in 17%, and micropapillary in 15%. The predominant nuclear grade was Grade I in 51%, Grade II in 49%, and Grade III in 0%. The median follow-up is 68 months. There have been three recurrences in the treated breast at a median time to failure of 30 months. The 5- and 8-year actuarial local recurrence rate is 6%. One patient recurred with invasive ductal cancer at 28 months, and the other two recurrences were DCIS at 30 and 50 months. All three patients were treated with salvage mastectomy. The patient who recurred locally with an invasive cancer developed metastasis and died at 64 months. The 5- and 8-year actuarial cause-specific survival rates are 100% and 97%, respectively. The following pathologic factors were analyzed for an association with local recurrence: predominant DCIS histology, predominant nuclear grade, and highest nuclear grade. Of these, the predominant nuclear grade was the best predictor of local recurrence (p = 0.070). No clinical or treatment related factor analyzed was associated with local recurrence. CONCLUSION: Our results indicate that excellent local control (94%) at 8 years is obtainable after CSRT in a mammographically detected population of patients with DCIS. The predominant nuclear grade was the only factor found that may be associated with local recurrence.

Adult↗

A new model for "accept or reject" strategies in off-line and on-line megavoltage treatment evaluation.

PURPOSE: With megavoltage on-line imaging, a temporal record of the treatment setup variation is made available during the course of radiotherapy. This work describes the theoretical framework where the imaging data is incorporated as feedback for deriving off-line and on-line "accept or reject" decisions to improve the quality of radiotherapy on an individual patient basis. METHODS AND MATERIALS: A dynamic model of treatment setup variation is developed to describe: (a) the variations of multifraction treatment position and (b) the variation of measurement. Based on this model, a confidence region of subsequent treatment position is estimated from measurements of previous treatment position. The confidence region is compared with an allowance region of the treatment position, representing the acceptable margin of setup variation. The difference of the two regions are then evaluated to derive off-line and on-line "accept or reject" treatment decisions. RESULTS: The model was simulated retrospectively using sequential daily images from different treatment sites. "Accept or reject" decisions were produced for on-line and off-line applications. The results also demonstrate the ability of the model to include the effects of setup variation that drifted during the course of treatment. CONCLUSION: The preliminary result demonstrates that "accept or reject" treatment decisions can be derived quantitatively from on-line imaging data. The model shows potential to guide the physician and therapist in implementing efficient and accurate treatment adjustments. Further work is required to test the model in the clinical setting.

Humans↗

A multileaf collimator field prescription preparation system for conventional radiotherapy.

PURPOSE: The purpose of this work is to develop a prescription preparation system for efficient field shaping using a multileaf collimator that can be used in community settings as well as research institutions. The efficiency advantage of the computer-controlled multileaf collimator, over cerrobend blocks, to shape radiation fields has been shown in conformal treatments, which typically require complete volumetric computerized tomographic data for three-dimensional radiation treatment planning--a utility not readily available to the general community. As a result, most patients today are treated with conventional radiation therapy. Therefore, we believe that it is very important to fully use the same efficiency advantage of multileaf collimator as a block replacement in conventional practice. METHODS AND MATERIAL: The multileaf collimator prescription preparation systems developed by us acquires prescription images from different sources, including film scanner, and radiation treatment planning systems. The multileaf collimator angle and leaf positions are set from the desired field contour defined on the prescription image, by minimizing the area discrepancies. Interactive graphical tools include manual adjustment of collimator angle and leaf positions, and definition of portions of the field edges that require maximal conformation. Data files of the final leaf positions are transferred to the multileaf collimator controller via a dedicated communication link. RESULTS: We have implemented the field prescription preparation system and a network model for integrating the multileaf collimator and other radiotherapy modalities for routine treatments. For routine plan evaluation, isodose contours measured with film in solid water phantom at prescription depth are overlaid on the prescription image. Preliminary study indicates that the efficiency advantage of the MLC over cerrobend blocks in conformal therapy also holds true for conventional treatments. CONCLUSION: Our model of computer-controlled prescription, evaluation, and treatment using multileaf collimators can be effectively implemented in both community settings and research institutions. The resultant increase in treatment efficiency and accuracy is now available for conventional radiotherapy.

Humans↗

Diagnostic analysis of the prolonged bluetongue virus RNA presence found in the blood of naturally infected cattle and experimentally infected sheep.

Bluetongue virus (BTV) RNA was detected by the polymerase chain reaction (PCR) in the blood of 24 naturally infected cattle as long as 160 days after the estimated date of infection. Blood samples from these animals and from 10 experimentally BTV-infected sheep, which also exhibited a prolonged hematologic BTV RNA presence, were concurrently evaluated for viral infectivity. Infectivity analyses were conducted using the sentinel sheep inoculation and embryonated chicken egg inoculation procedures. Blood specimens from the experimental sheep 50, 56, 71, and 89 days after BTV inoculation were uniformly negative for viral infectivity despite their uniformly positive status with PCR evaluation. Three collections of blood from the naturally infected cattle at least 100, 135, and 160 days after infection also revealed no recoverable viral infectivity but an initially high and progressively decreasing prevalence of BTV with the PCR technique. These retrospective epidemiologic and prospective experimental approaches were concordant in that both studies demonstrated consistent discrepancies between the viral infectivity and the PCR diagnostic data. The significance of these discrepancies is discussed with respect to Koch's postulates and with respect to the possibility that the biological vector of BTV (Culicoides variipennis) may recover BTV infectivity from PCR-positive but virus isolation-negative blood.

Animals↗

The use of iodine-125 seeds as a substitute for iridium-192 seeds in temporary interstitial breast implants.

PURPOSE: We have previously reported that the use of iodine-125 seeds in temporary plastic tube interstitial implants may be more advantageous than iridium-192 seeds due to less patient and personnel radiation exposure, reduced shielding requirements, and significant dosimetric advantages. The impact of this isotope on the rate of local control and cosmetic outcome in patients with early stage breast cancer treated with interstitial implants for their irradiation "boost" remains to be defined. METHODS AND MATERIALS: We reviewed the treatment outcome of 402 consecutive cases of Stage I and II breast cancer undergoing breast conserving therapy between 1/1/80 and 12/31/87. All patients underwent excisional biopsy and received 45-50 Gy to the entire breast followed by a boost to the tumor bed using either electrons (104 patients), photons (15 patients), or an interstitial implant with either iridium-192 (197 patients) or iodine-125 (86 patients) to at least 60 Gy. Iodine-125 implants were primarily performed in patients with significant risk factors for local recurrence (71%) or in patients with large breasts (17%). Local tumor control and cosmetic outcome were assessed and contrasted between patients boosted with each modality. RESULTS: With a median follow-up of 59.3 months, 18 (4.5%) patients developed a recurrence of the tumor in the treated breast (4.4% 5-year actuarial rate). No statistically significant differences in the 5-year actuarial rate of local recurrence were noted between patients boosted with either iodine-125 (3.0%), iridium-192 (3.8%), electrons (5.4%), or photons (0%). Likewise, no significant differences in the percentage of patients obtaining good/excellent cosmetic results were noted between iodine-125 (93%), iridium-192 (88%), electrons (90%), or photons (82%). CONCLUSION: We conclude that patients with Stage I and II breast cancer undergoing breast conserving therapy and judged to be candidates for boosts with interstitial implants can be effectively treated with iodine-125 seeds. Use of this isotope results in less patient and personnel irradiation exposure and a better dose distribution than iridium-192, since dose optimization can be routinely employed. Overall, local control and cosmetic outcome have been excellent and are similar to either iridium-192, electrons, or photons.

Brachytherapy↗

Preliminary observations on the use of the Palmaz stent in the distal portion of the abdominal aorta.

The opportunities to avoid surgical treatment of distal abdominal aortic occlusive disease are expanding because of the proliferation in catheter-based techniques. Since January 1990, 24 symptomatic patients with distal abdominal disorders have been treated percutaneously with balloon angioplasty and intraluminal stenting. A total of 38 Palmaz stents were deployed at distal abdominal aortic sites; 21 additional iliac stents were implanted. After the procedure all patients improved clinically, and 83% (21/24) improved by objective measurement (average ABI 0.93 +/- 0.21). Three access-related complications occurred (two hematomas, one thrombus), but no complications were related to the stents. At up to 29 months of follow-up (average 10.3 +/- 6.7 months), clinical improvement persists in all patients (average ABI 0.93 +/- 0.22). In 11 patients eligible for follow-up aortography, all aortic stents are patent without evidence of restenosis. With the low likelihood for restenosis in the abdominal aorta, the long-term outcome of aortic stenting looks promising and may equal or surpass that found in the iliac region.

Aged↗

Nucleotide sequence of barley stripe mosaic virus RNA alpha: RNA alpha encodes a single polypeptide with homology to corresponding proteins from other viruses.

The complete nucleotide sequence of RNA alpha from the Type strain of barley stripe mosaic virus has been determined. The RNA is 3768 nucleotides long and contains a single open reading frame which codes for a polypeptide of 1139 amino acids (mw 129,634). The open reading frame is flanked by a 5'-terminal sequence of 91 nucleotides and a 3'-nontranslated region composed of a short poly(A) tract followed by a 238-nucleotide tRNA-like structure. The amino acid sequence of the polypeptide (alpha a) encoded by the open reading frame has homology with the TMV 126K protein and with related polypeptides from other viruses. The carboxy-terminal portion of the alpha a polypeptide also has limited homology with the 58K (beta b) protein encoded by BSMV RNA beta and includes a consensus sequence found in mononucleotide-binding polypeptides.

Amino Acid Sequence↗

The nevoid basal cell carcinoma syndrome--Gorlin's syndrome. Multiple jaw cysts and skin cancer.

The nevoid basal cell carcinoma (NBS) syndrome with its characteristic multiple cysts of the jaws and skin cancer is of great interest to the dentist, the dermatologist and the oncologist. The dentist may have the opportunity of making an early diagnosis as the multiple cysts appear mostly in the ramus of the lower jaw. There is a great risk of recurrence as surgical removal is often very complicated. The disease is hereditary and is transmitted through females. The skin cancer can in most cases be treated surgically. It is essential that the family with the syndrome is investigated regularly and at periods of about six months.

Adult↗

Nucleotide sequence and genetic organization of barley stripe mosaic virus RNA gamma.

The complete nucleotide sequences of RNA gamma from the Type and ND18 strains of barley stripe mosaic virus (BSMV) have been determined. The sequences are 3164 (Type) and 2791 (ND18) nucleotides in length. Both sequences contain a 5'-noncoding region (87 or 88 nucleotides) which is followed by a long open reading frame (ORF1). A 42-nucleotide intercistronic region separates ORF1 from a second, shorter open reading frame (ORF2) located near the 3'-end of the RNA. There is a high degree of homology between the Type and ND18 strains in the nucleotide sequence of ORF1. However, the Type strain contains a 366 nucleotide direct tandem repeat within ORF1 which is absent in the ND18 strain. Consequently, the predicted translation product of Type RNA gamma ORF1 (mol wt 87,312) is significantly larger than that of ND18 RNA gamma ORF1 (mol wt 74,011). The amino acid sequence of the ORF1 polypeptide contains homologies with putative RNA polymerases from other RNA viruses, suggesting that this protein may function in replication of the BSMV genome. The nucleotide sequence of RNA gamma ORF2 is nearly identical in the Type and ND18 strains. ORF2 codes for a polypeptide with a predicted molecular weight of 17,209 (Type) or 17,074 (ND18) which is known to be translated from a subgenomic (sg) RNA. The initiation point of this sgRNA has been mapped to a location 27 nucleotides upstream of the ORF2 initiation codon in the intercistronic region between ORF1 and ORF2. The sgRNA is not coterminal with the 3'-end of the genomic RNA, but instead contains heterogeneous poly(A) termini up to 150 nucleotides long (J. Stanley, R. Hanau, and A. O. Jackson, 1984, Virology 139, 375-383). In the genomic RNA gamma, ORF2 is followed by a short poly(A) tract and a 238-nucleotide tRNA-like structure.

Amino Acid Sequence↗

The complete nucleotide sequence of RNA beta from the type strain of barley stripe mosaic virus.

The complete nucleotide sequence of RNA beta from the type strain of barley stripe mosaic virus (BSMV) has been determined. The sequence is 3289 nucleotides in length and contains four open reading frames (ORFs) which code for proteins of Mr 22,147 (ORF1), Mr 58,098 (ORF2), Mr 17,378 (ORF3), and Mr 14,119 (ORF4). The predicted N-terminal amino acid sequence of the polypeptide encoded by the ORF nearest the 5'-end of the RNA (ORF1) is identical (after the initiator methionine) to the published N-terminal amino acid sequence of BSMV coat protein for 29 of the first 30 amino acids. ORF2 occupies the central portion of the coding region of RNA beta and ORF3 is located at the 3'-end. The ORF4 sequence overlaps the 3'-region of ORF2 and the 5'-region of ORF3 and differs in codon usage from the other three RNA beta ORFs. The coding region of RNA beta is followed by a poly(A) tract and a 238 nucleotide tRNA-like structure which are common to all three BSMV genomic RNAs.

Amino Acid Sequence↗

Appearance of different lymphoid cells in synovial tissue and in peripheral blood during the course of collagen II-induced arthritis in rats.

The involvement of different sets of lymphoid cells in the development of collagen II-induced arthritis in rats was studied by means of immunohistochemical analyses on frozen sections of tissue from joint biopsy specimens taken at different phases of arthritis development. Particular attention was paid to cells involved in early pannus formation. Accumulation of anti-Ia-reactive cells close to the cartilage surface was seen early in the development of pannus, and the anti-Ia reactive cells could in later phases be seen infiltrating cartilage and crowding bone surfaces at sites of marginal erosion. With the help of monoclonal anti-T-cell subset antibodies and rabbit anti-rat immunoglobulin antiserum, it was demonstrated that synovial infiltration of T lymphocytes, particularly W3/25-reactive T "helper" cells, occurs very early in the development of arthritis, whereas a moderate increase of Ox 8-positive 'suppressor/cytotoxic' T cells and a small number of B cells and plasma cells are seen later in the course of the disease. Levels of Ia-expressing cells and of T cells belonging to different subsets were recorded in peripheral blood by means of immunocytochemical analyses on cell smears; no significant deviations from normal levels were seen during the development of arthritis.

Animals↗