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Biomedical subjects

J Michalski

Publications and source records attributed to J Michalski.

At least 37 records · Page 2Linked to original sources
PubMed1997

Adaptive modification of treatment planning to minimize the deleterious effects of treatment setup errors.

PURPOSE: Using daily setup variation measured from an electronic portal imaging device (EPID), radiation treatment of the individual patient can be adaptively reoptimized during the course of therapy. In this study, daily portal images were retrospectively examined to: (a) determine the number of initial days of portal imaging required to give adequate prediction of the systematic and random setup errors; and (b) explore the potential of using the prediction as feedback to reoptimize the individual treatment part-way through the treatment course. METHODS AND MATERIALS: Daily portal images of 64 cancer patients, whose treatment position was not adjusted during the course of treatment, were obtained from two independent clinics with similar setup procedures. Systematic and random setup errors for each patient were predicted using different numbers of initial portal measurements. The statistical confidence of the predictions was tested to determine the number of daily portal measurements needed to give reasonable predictions. Two treatment processes were simulated to examine the potential opportunity for setup margin reduction and dose escalation. The first process mimicked a conventional treatment. A constant margin was assigned to each treatment field to compensate for the average setup error of the patient population. A treatment dose was then prescribed with reference to a fixed normal tissue tolerance, and then fixed in the entire course of treatment. In the second process, the same treatment fields and prescribed dose were used only for the initial plan and treatment. After several initial days of treatments, the treatment field shape and position were assumed to be adaptively modified using a computer-controlled multileaf collimator (MLC) in light of the predicted systematic and random setup errors. The prescribed dose was then escalated until the same normal tissue tolerance, as determined in the first treatment process, was reached. RESULTS: The systematic setup error and the random setup error were predicted to be within +/-1 mm for the former and +/-0.5 mm for the latter at a > or = 95% confidence level using < or = 9 initial daily portal measurements. In the study, a large number of patients could be treated using a smaller field margin if the adaptive modification process were used. Simulation of the adaptive modification process for prostate treatment demonstrates that additional treatment dose could be safely applied to 64% of patients. CONCLUSION: The adaptive modification process represents a different approach for use of on-line portal images. The portal imaging information from the initial treatments is used as feedback for reoptimization of the treatment plan, rather than adjustment of the treatment setup. Results from the retrospective study show that the treatment of individual patient can be improved with the adaptive modification process.

Algorithms↗
PubMed1997

Volunteer studies investigating the safety and efficacy of live oral El Tor Vibrio cholerae O1 vaccine strain CVD 111.

A live oral cholera vaccine should ideally protect against both classical and El Tor biotypes of Vibrio cholerae O1. An El Tor biotype vaccine strain, therefore, would complement classical cholera vaccine strain CVD 103-HgR, a strain already in use in some countries. In this study, 25 healthy adult volunteers received a single dose of 10s colony-forming units of El Tor vaccine strain CVD 111, a derivative of El Tor Ogawa strain N16117 deleted in the virulence cassette. Three (12%) volunteers developed mild diarrhea (mean stool volume = 813 ml) but no systemic symptoms; 23 (92%) of the 25 volunteers developed serum vibriocidal antibodies (geometric mean titer = 1:2,291). Five weeks after vaccination, 18 vaccines and eight uninimunized control volunteers underwent wild-type challenge with El Tor Ogawa strain 3008. Three (16.7%) of 18 vaccinees and seven (87.5%) of eight controls developed diarrhea (P = 0.001) (vaccine efficacy = 80.9%). Further studies are underway to determine a dosage of CVD 111 that will be more clinically acceptable but equally immunogenic and protective.

Administration, Oral↗
PubMed1996

Nonrandomized evaluation of pelvic lymph node irradiation in localized carcinoma of the prostate.

PURPOSE: A great deal of controversy exists regarding the potential benefit of pelvic lymph node irradiation compared with treatment to the prostate only in patients with localized prostate cancer. Despite numerous reports, including a randomized study, this issue has not been completely elucidated. METHODS AND MATERIALS: A total of 963 patients with histologically proven localized adenocarcinoma of the prostate treated with definitive radiation therapy alone were analyzed. Median follow-up was 6.5 years (minimum: 2 years, maximum: 22 years). Pelvic lymph nodes received 40 to 55 Gy with anteroposterior/posteroanterior and sometimes lateral stationary portals in 1.8 Gy daily fractions; an additional dose was delivered to the prostate with 120 degrees bilateral are rotation to complete doses of 65 to 68 Gy for Stage A2 and B tumors and 68 to 71 Gy for Stage C tumors. The same total doses were delivered with smaller fields when the prostate only was treated. RESULTS: In Stage A2 (T1b,c) the 10-year clinical pelvic failure rate was 16% regardless of the volume irradiated or tumor differentiation. With Stage B (T2) well- or moderately differentiated tumors, the 10-year pelvic failure rates were 22% when pelvic lymph nodes were irradiated and 32% when prostate only was irradiated (p = 0.41). With Stage A2 (T1b,c) and B (T2) poorly differentiated tumors, the 10-year pelvic failure rates were 32% and 7%, respectively (p = 0.72). With clinical stage C (T3) well-differentiated tumors treated with 50 to 55 Gy to pelvic lymph nodes, the pelvic failure rate was 22% compared with 37% in those receiving 40 to 45 Gy (p < or = 0.07). A significant reduction in pelvic failures was noted with Stage C poorly differentiated tumors when the pelvic lymph nodes received doses higher than 50 Gy (23%) compared with lower doses (46%) (p < or = 0.01). Volume or doses of irradiation did not influence incidence of distant metastases in any stage or tumor differentiation group. Disease-free survival did not correlate with volume treated in any clinical stage or tumor differentiation group. In 317 patients on whom pretreatment prostate-specific antigen levels were available, there is a suggestion that those treated to the pelvic lymph nodes had a higher chemical disease-free survival than those receiving prostate irradiation only. Follow-up is short, and differences are not statistically significant in any of the groups. Morbidity of therapy was slightly higher in patients treated to the pelvic lymph nodes, but in Stages A2 (T1b,c) and B (T2) differences are not statistically significant (4 to 6%). Stage C patients treated to the pelvic lymph nodes with 50 Gy had a 12% incidence of Grade 2 rectosigmoid morbidity compared with 6% in those treated with 40 Gy (p = 0.26). CONCLUSIONS: In this retrospective analysis, pelvic lymph node irradiation did not influence local/pelvic tumor control, incidence of distant metastases, or disease-free survival in patients with clinical Stage A2 (T1b,c) or B (T2) localized carcinoma of the prostate. In patients with Stage C (T3) disease, irradiation of the pelvic lymph nodes with doses of 50 to 55 Gy resulted in a lower incidence of pelvic recurrences and improved disease-free survival. Morbidity of therapy was acceptable, although patients with Stage C disease had a somewhat higher incidence of Grade 2 rectosigmoid morbidity. Pelvic lymph node irradiation is being elucidated in properly designed prospective, randomized protocols.

Adenocarcinoma↗
PubMed1995

Tumor and target delineation: current research and future challenges.

In the past decade, significant progress has been made in the imaging of tumors, three dimensional (3D) treatment planning, and radiation treatment delivery. At this time one of the greatest challenges for conformal radiation therapy is the accurate delineation of tumor and target volumes. The physician encounters many uncertainties in the process of defining both tumor and target. The sources of these uncertainties are discussed, as well as the issues requiring study to reduce these uncertainties.

Forecasting↗
PubMed1995

The cumulative verification image analysis tool for offline evaluation of portal images.

PURPOSE: Daily portal images acquired using electronic portal imaging devices contain important information about the setup variation of the individual patient. The data can be used to evaluate the treatment and to derive correction for the individual patient. The large volume of images also require software tools for efficient analysis. This article describes the approach of cumulative verification image analysis (CVIA) specifically designed as an offline tool to extract quantitative information from daily portal images. METHODS AND MATERIALS: The user interface, image and graphics display, and algorithms of the CVIA tool have been implemented in ANSCI C using the X Window graphics standards. The tool consists of three major components: (a) definition of treatment geometry and anatomical information; (b) registration of portal images with a reference image to determine setup variation; and (c) quantitative analysis of all setup variation measurements. The CVIA tool is not automated. User interaction is required and preferred. Successful alignment of anatomies on portal images at present remains mostly dependent on clinical judgment. Predefined templates of block shapes and anatomies are used for image registration to enhance efficiency, taking advantage of the fact that much of the tool's operation is repeated in the analysis of daily portal images. RESULTS: The CVIA tool is portable and has been implemented on workstations with different operating systems. Analysis of 20 sequential daily portal images can be completed in less than 1 h. The temporal information is used to characterize setup variation in terms of its systematic, random and time-dependent components. The cumulative information is used to derive block overlap isofrequency distributions (BOIDs), which quantify the effective coverage of the prescribed treatment area throughout the course of treatment. Finally, a set of software utilities is available to facilitate feedback of the information for treatment plan recalculation and to test various decision strategies for treatment adjustment. CONCLUSIONS: The CVIA tool provides comprehensive analysis of daily images acquired with electronic portal imaging devices. Its offline approach allows characterization of the nature of setup variation for the individual patient that would have been difficult to deduce using only a few daily or weekly portal images. Distribution of the tool will help establish an important database of setup variation from many clinics. The information derived from CVIA can also serve as the foundation to integrate treatment verification, treatment planning, and treatment delivery.

Computer Peripherals↗
PubMed1995

Initial clinical studies of CVD 112 Vibrio cholerae O139 live oral vaccine: safety and efficacy against experimental challenge.

Since October 1992, epidemics of cholera associated with Vibrio cholerae O group 139 have occurred in India, Bangladesh, and much of the rest of Asia. A volunteer model was used to determine the safety, immunogenicity, and efficacy of an attenuated delta ctxA delta zot delta ace delta cep V. cholerae O139 vaccine strain, designated CVD 112. Six volunteers received 10(6) cfu and 6 received 10(8) cfu of CVD 112. No subject who received the 10(6) dose had diarrhea or other severe symptoms after vaccination; 3 vaccinees developed mild diarrhea (mean stool volume, 648 mL) after receiving the higher dose. Five weeks after vaccination, 8 vaccinees and 15 unvaccinated control subjects underwent challenge with 10(6) cfu of wild type V. cholerae O139 AI1837. One vaccinee (13%) and 12 control subjects (80%) developed diarrhea after challenge (P = .003). The short-term protective efficacy conferred by vaccine strain CVD 112 was 84% and was remarkably similar to that conferred by primary wild type clinical infection (80%).

Administration, Oral↗
PubMed1995

Radiation therapy in the treatment of localized prostate cancer: an alternative to an emerging consensus.

Optimal treatment for patients with localized carcinoma of prostate is controversial. Radiation therapy is an established modality; reports indicate that results are comparable to those of radical prostatectomy. A retrospective review was carried out of 963 patients with carcinoma of the prostate treated with definitive irradiation (65 to 71 Gy in 6.5 to 7 weeks). Survival, incidence of local recurrence and distant metastases, and postirradiation PSA data were analyzed. Ten-year disease-free survival with external irradiation was 100% for clinical stage A1 (T1a), 69% for stage A2 (T1b,c), 57% for clinical stage B (T2), and 41% for stage C (T3). Initial PSA level closely correlated with probability of freedom from chemical failure (PSA elevation) after definitive irradiation in 317 patients with stage T1b,c and T2 tumors (96% and 89%, respectively, with initial PSA of < 10 ng/ml and 75% and 65% with higher PSA levels). Although modern irradiation techniques produce results comparable to those of radical prostatectomy in localized prostate carcinoma, we must continue to critically assess treatment policies, develop appropriately designed prospective clinical trials, and define optimal management of these patients.

Disease-Free Survival↗
PubMed1994

recA mutations reduce adherence and colonization by classical and El Tor strains of Vibrio cholerae.

Two recA mutants of Vibrio cholerae (classical and El Tor biotypes) were constructed by disruption of the wild-type recA gene with mutated recA sequences of V. cholerae cloned in the suicide vector pGP704. Mutants defective in the recA gene were compared with their respective RecA+ parent strains with regard to their adherence to isolated rabbit intestine and colonization of intestine of infant mice. The recA mutation in V. cholerae was found to diminish adherence and markedly affected colonization.

Animals↗
PubMed1994

Potential for reacquisition of cholera enterotoxin genes by attenuated Vibrio cholerae vaccine strain CVD 103-HgR.

The potential for reacquisition of ctxA genes by attenuated Vibrio cholerae O1 vaccine strain CVD 103-HgR was examined by performing a series of mating experiments under a variety of in vivo and in vitro conditions. We found no evidence that CVD 103-HgR could reacquire ctxA genes from wild-type V. cholerae O1 strains. However, if the donor V. cholerae O1 strains were genetically manipulated to add genes that allow chromosomal gene transfer, then ctxA sequences could be acquired by CVD 103-HgR. The minimal excretion of CVD 103-HgR by vaccinees and the refractoriness to reacquisition of ctxA sequences suggest that this well-tolerated, highly immunogenic live oral cholera vaccine will have a minimal environmental impact.

Cholera Vaccines↗
PubMed1993

Construction of genetically marked Vibrio cholerae O1 vaccine strains.

Attenuated Vibrio cholerae O1 vaccine strains lacking the gene encoding the A subunit of cholera toxin have proven efficacious in preventing experimental cholera. As these strains move from closed, contained testing environments to large-scale field trials, a readily assayable phenotypic trait to distinguish a vaccine strain from wild-type V. cholerae O1 is desirable. We have constructed three derivatives of the attenuated V. cholerae strain CVD 103 which carry a mercury resistance or urease marker in the hlyA gene. CVD 103-HgR was constructed using a protracted marker-exchange procedure; this strain was found to have somewhat lowered colonisation efficiency in infant mice in comparison to its parent strain, CVD 103. The insertion of the resistance marker was repeated using a suicide vector system; CVD 103-HgR2 was found to colonise infant mice as efficiently as CVD 103. Strain CVD 103-UR, in which sequences encoding urease were inserted using a suicide vector, also colonised infant mice as well as CVD 103. The genetically marked strains CVD 103-HgR, CVD 103-HgR2 and CVD 103-UR form the basis for a generation of defined oral vaccines that may give single-dose, long-lasting protection to populations at risk from cholera.

Animals↗
PubMed1993

Accessory cholera enterotoxin (Ace), the third toxin of a Vibrio cholerae virulence cassette.

Vibrio cholerae causes the potentially lethal disease cholera through the elaboration of the intestinal secretogen cholera toxin. A second toxin of V. cholerae, Zot, decreases intestinal tissue resistance by modifying intercellular tight junctions. In this report, a third toxin of V. cholerae, Ace (accessory cholera enterotoxin), is described. Ace increases short-circuit current in Ussing chambers and causes fluid secretion in ligated rabbit ileal loops. The predicted protein sequence of Ace shows striking similarity to eukaryotic ion-transporting ATPases, including the product of the cystic fibrosis gene. The gene encoding Ace is located immediately upstream of the genes encoding Zot and cholera toxin. The ctx, zot, and ace genes, which are located on a dynamic sector of the chromosome, comprise a V. cholerae "virulence cassette."

Amino Acid Sequence↗
PubMed1993

Safety and immunogenicity of live oral cholera vaccine candidate CVD 110, a delta ctxA delta zot delta ace derivative of El Tor Ogawa Vibrio cholerae.

The current pandemic of cholera is caused primarily by Vibrio cholerae O1 of the El Tor biotype. Live attenuated classical biotype V. cholerae vaccine strains prevent severe and moderate cholera due to either biotype in challenged volunteers but may provide less protection against mild cholera due to El Tor organisms. CVD 110, a new ctxA-deleted vaccine strain derived from an El Tor Ogawa parent, lacks zona occludens toxin (Zot), accessory cholera enterotoxin (Ace), and hemolysin/enterotoxin. Ten healthy adult volunteers were given 10(8) cfu of CVD 110 with buffer; 7 developed diarrhea (mean stool volume, 861 mL). Vaccine organisms were shed in stool by all vaccines and were recovered from duodenal fluid in three-quarters of vaccinees. After vaccination, the geometric mean peak reciprocal vibriocidal titer among vaccinees was 17,829. CVD 110 is a powerful immunogen but insufficiently attenuated despite the absence of known potential enterotoxins of V. cholerae. Another unrecognized toxin or colonization alone may be responsible for diarrhea after ingestion of this strain.

Administration, Oral↗
PubMed1993

CVD110, an attenuated Vibrio cholerae O1 El Tor live oral vaccine strain.

The recent expansion of the seventh cholera pandemic into South America emphasizes the need for a safe, long-lasting, protective, and nonreactogenic vaccine for this disease. Since the predominant Vibrio cholerae O1 strains in the world today are of the El Tor biotype, a bivalent vaccine containing both classical and El Tor biotypes may be desirable. We have constructed a new oral vaccine candidate, V. cholerae CVD110 El Tor, Ogawa, from which all toxin genes so far identified in V. cholerae have been deleted. Three of these genes, those encoding cholera toxin (ctx), zonula occludens toxin (zot), and accessory cholera enterotoxin (ace), are located on a 4.5-kb virulence cassette flanked by repetitive sequences (RS1 elements). Homologous recombination between these RS1 elements resulted in the deletion of this virulence cassette to yield V. cholerae CVD109. Insertion of genes encoding mercury resistance (mer) and the cholera toxin B subunit (ctxB) into the hemolysin locus (hlyA) produced CVD110. This insertion serves three purpose. (i) It genetically tags the vaccine strain so as to distinguish it from wild-type V. cholerae O1. (ii) It produces cholera toxin B subunit in order to elicit antitoxic immunity. (iii) It inactivates the hemolysin gene, rendering the strain nonhemolytic on sheep erythrocyte plates. Supernatants from V. cholerae CVD110 cultures are nonreactogenic when assayed in Ussing chambers.

Bacterial Toxins↗