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R Nath

Publications and source records attributed to R Nath.

At least 55 records · Page 3Linked to original sources
PubMed2000

A model for photon detection and dosimetry with superheated emulsions.

A model is presented for the analysis and prediction of the photon response of detectors based on superheated emulsions of light halocarbons in tissue equivalent gels. It is shown that on the basis of a nondimensional thermodynamic quantity, called reduced superheat, it is possible to identify the degree of superheat, or the operating temperature, corresponding to the photon sensitization of the emulsions. Moreover, on the basis of the mass energy absorption coefficients, it is possible to determine the energy dependence of the photon response. The vaporization energy necessary for bubble nucleation is estimated by means of the thermal spike theory developed for bubble chambers. The energy deposition requirements are consistent with the energy transferred by secondary electrons at the end of their range in the halocarbons. These findings provide design criteria for photon detectors based on superheated emulsions. It is shown that light halocarbons of low effective atomic numbers present the best dosimetric properties. In particular, by manufacturing superheated emulsions with octafluoropropane, or halocarbon R-218, photon sensitivity is achieved at room temperature along with a fairly constant air-kerma response.

Emulsions↗
PubMed2000

Recommendations of the American Association of Physicists in Medicine on 103Pd interstitial source calibration and dosimetry: implications for dose specification and prescription.

The National Institute of Standards and Technology (NIST) introduced a national standard for air kerma strength of the ThreaSeed Model 200 103Pd source (the only 103Pd seed available until 1999) in early 1999. Correct implementation of the NIST-99 standard requires the use of dose rate constants normalized to this same standard. Prior to the availability of this standard, the vendor's calibration procedure consisted of intercomparing Model 200 seeds with a 109Cd source with a NIST-traceable activity calibration. The AAPM undertook a comprehensive review of 103Pd source dosimetry including (i) comparison of the vendor and NIST-99 calibration standards; (ii) comparison of original Task Group 43 dosimetry parameters with more recent studies; (iii) evaluation of the vendor's calibration history; and (iv) evaluation of administered-to-prescribed dose ratios from the introduction of 103Pd sources in 1987 to the present. This review indicates that for a prescribed dose of 115 Gy, the administered doses were (a) 124 Gy for the period 1988-1997 and (b) 135 Gy for the period 1997-1999. The AAPM recommends that the following three steps should be undertaken concurrently to implement correctly the 1999 dosimetry data and NIST-99 standard for 103Pd source: (1) the vendor should provide calibrations in terms of air kerma strength traceable to NIST-99 standard, (2) the medical physicist should update the treatment planning system with properly normalized (to NIST-99) dosimetry parameters for the selected 103Pd source model, and (3) the radiation oncologist in collaboration with the medical physicist should decide which clinical experience they wish to duplicate; the one prior to 1997 or the one from 1997 to 1999. If the intent is to duplicate the experience prior to 1997, which is backed by the long-term follow-up and published outcome studies, then the prior prescriptions of 115 Gy should be replaced by 124 Gy to duplicate that experience.

Brachytherapy↗
PubMed2000

Measurement of dose-rate constant for 103Pd seeds with air kerma strength calibration based upon a primary national standard.

Recent developments in the past two years require a significant change in the dosimetry of 103Pd brachytherapy sources (Theraseed model 200, manufactured by Theragenics Corp., Atlanta, GA). Since their introduction in 1987, the air kerma strength of 103Pd sources for interstitial brachytherapy has been determined using a system of apparent activity measurement based upon the measurement of photon fluence at a reference distance along the transverse axis of the source free in air, using a NaI (T1) scintillation detector at the manufacturer's facilities. This detection system has been calibrated against a National Institute of Standards and Technology (NIST)-traceable activity standard of a 109Cd source. This system produced a highly consistent standard (within +/-2%) for over 12 years, with the exception of the last 109Cd source change in September 1997, which resulted in a change of 9% from the original 1987 standard. The second major development affecting 103Pd dosimetry is that on 13 January 1999 a primary national standard for the air kerma strength of 103Pd seeds was developed by NIST. This primary standard is based upon an absolute measurement of air kerma rate free in air at a reference distance from the source along its transverse axis using a wide angle free air chamber (WAFAC). In order to implement this new standard for the calibration of source strength in clinical dosimetry for interstitial implants, it is necessary to measure the dose-rate constant for the 103Pd seeds using a calibration of source strength based on the NIST 99 standard. In this work, a measurement of the dose-rate constant using lithium fluoride (LiF) thermoluminescent dosimeters (TLDs) in a water equivalent solid phantom is reported. The measured value of this constant is 0.65 +/- 0.05 cGy h(-1) U(-1), where the unit air kerma strength is 1 U = 1 cGy h(-1) cm2 = 1 microGy h(-1) m2, and is directly traceable to the NIST 99 standard. The implementation of the NIST 99 standard for 103Pd should be accompanied by a simultaneous adoption of the new dose-rate constant reported here. No changes in radial dose function, anisotropy function, anisotropy factor, and geometry function are needed. However, a change in prescribed dose may be necessary to deliver the same physical dose as before.

Calibration↗
PubMed2000

Self-reported marijuana effects and characteristics of 100 San Francisco medical marijuana club members.

In order to assess the relationships between medical marijuana users' reasons for use, side effects, and drug use patterns, 100 participants were recruited from the San Francisco Cannabis Cultivator's Club. Users, averaging 14 years pre-illness use, perceived marijuana to be more effective than other treatments and to have less severe side effects. Urine drug assays showed recent use of other drugs, particularly stimulants. History of substance abuse or dependence and other psychiatric disorders was common. Those with greater past dependence on other drugs thought marijuana to be more effective but also reported worse side effects and quality of life. Quality of life was associated more with marijuana side effects rating than effectiveness. Patients reported potentially serious marijuana side effects on some questionnaires but not others. Inconsistencies in reporting made interpretation of results difficult. Physician supervision of medical marijuana use would allow more effective monitoring of therapeutic and unwanted effects, some unrecognized by patients.

Adult↗
PubMed2000

HPV16 E6 oncogene variants in women with cervical intraepithelial neoplasia.

Human papillomaviruses (HPVs) are strongly associated with the development of high grade cervical intraepithelial neoplasia (CIN) and cervical carcinoma, with between 40-80% of patients with cervical carcinoma being attributed to a single HPV type, HPV16 depending on the methods used and geographical location of the particular study [van den Brule et al., 1996]. An HPV16 E6 variant has been described which is strongly associated with high grade CIN [Ellis et al., 1997] and with the human leukocyte antigen (HLA)-B7 genotype in women with cervical carcinoma where HLA-B7 positive patients were demonstrated to have a significantly poorer clinical outcome [Ellis et al., 1995]. To determine whether this HPV16 E6 variant might play a significant role in the pathogenesis of cervical disease, 174 HPV16 positive women were selected from those attending the colposcopy clinics of Guy's and St Thomas' Hospital Trust following polymerase chain reaction (PCR) amplification of HPV16 L1 or E5 DNAs from cervical brush swabs or fixed biopsy tissue. HPV16 E6 DNA was amplified by PCR and the variant sequence was identified by Msp 1 restriction enzyme digestion, as the nucleotide substitution creates an additional unique Msp 1 site. The study group comprised 29 normal controls, 7 women with borderline cytology, 123 women with cervical dysplasia and 12 women with cervical cancer. 101/174 (58%) of these women had amplifiable E6 DNA and restriction enzyme digestion was performed on 95 of these. The variant E6 sequence was identified in 3/95 (3%) individuals, two of whom had normal histology and one had a CIN II lesion. Wild type E6 sequence was identified in the remaining 92/95 (97%) individuals. These data suggest that this particular E6 variant does not play a major role in the pathogenesis of HPV16 related cervical disease in women living in the South London area.

DNA, Viral↗
PubMed2000

Raised platelet thiobarbituric acid-reacting substances in proliferative Eales' disease.

BACKGROUND: Platelets are an elective site for oxidative stress owing to their high content of polyunsaturated fatty acid. Increased lipid peroxidation and elevated platelet thiobarbituric acid-reacting substances (TBARS) signal oxidative stress. This possibly leads to retinal neovascularization in Eales' disease. METHODS: TBARS levels were estimated in consecutive cases of Eales' disease with neovascularisation (n = 26), Eales' disease without neovascularisation (n = 17) and healthy controls (n = 17). RESULTS: Platelet TBARS levels in the cases of Eales' disease with neovascularisation, Eales' disease without neovascularisation, and healthy controls were 0.66 +/- 0.1, 0.57 +/- 0.11 and 0.42 +/- 0.14 n moles TBARS formed/hour/10(8) platelets respectively. Student's t-test showed a significant increase in platelet TBARS levels in cases with neovascularisation as compared to cases without neovascularization (p < 0.05) and healthy controls (p < 0.01). CONCLUSION: The increase in platelet TBARS levels in proliferative Eales' disease is consistent with an emerging view that lipid peroxides may be associated with retinal neovascularisation.

Adolescent↗
PubMed1999

Optimum timing for image-based dose evaluation of 125I and 103PD prostate seed implants.

PURPOSE/OBJECTIVE: Image-based dose evaluation of permanent brachytherapy implants for prostate cancer is important for optimal patient management after implantation. Because of edema caused by the surgical procedure in the implantation, if the dose evaluation is based on the images obtained too early after implantation, dose coverage will usually be underestimated. Conversely, if the images are obtained too late, the dose coverage will be overestimated. This study uses a biomathematical model to simulate edema and its resolution on 29 patients, so that the optimum time to obtain image scans and perform dose evaluation can be investigated and estimated. METHODS AND MATERIALS: Edema of a prostate and its resolution has been shown to follow an exponential function V(t) = V(0)(1 + deltaV[e-0.693t/Te - 1]) where deltaV is the initial relative increase in the prostate volume due to edema (and is related to edema magnitude), and Te (edema half-life) is the time for the edema to decrease by half in volume. In this study, edema was simulated by increasing the volume of preimplant prostate (obtained from ultrasound volume study) to a given magnitude of edema. Similarly, the locations of planned seeds were changed to their corresponding locations in the edematous prostate proportionally. The edema was then allowed to resolve according to the exponential function. The correct dose distribution was calculated by taking into account the dynamic variations of the prostate volume, seed locations, and source strengths with respect to time. Dose volume histograms (DVHs) were then generated from this dose distribution. The conventional postimplant DVHs, which assume the prostate volume and seed locations are as in the image scans and constant in time, were also calculated based on the simulated image scans for various days postimplantation. The conventional DVHs of prostate on various days after implantation were compared to the DVH calculated assuming dynamic conditions. The optimum timing for conventional postimplant dose evaluation was identified as the time at which a minimum difference between the conventional DVH and the dynamic model DVH was achieved. The analysis was done on 29 prostate seed implant patients for both 125I and 103Pd. The edema magnitude was assumed to be 30%, 40%, 50%, 75%, and 100% of original prostate volume, and the half-life of edema was assumed to be 4, 7, 10, 15, 20, and 25 days. In this study, the original volume of prostate varied from 17 cm3 to 91 cm3, and number of seeds in the implants varied from 57 to 119. RESULTS: The optimum timing was mainly dependent on the half-lives of edema and radionuclides, and varied slightly with edema magnitude, prostate volume, and number of seeds. It can be expressed as a function of edema half-life in the form of C0 + C1exp(-C2Te). However, if the dose evaluation was performed based on the image scans taken too early or too late, the error became larger, as the edema magnitude was larger. By averaging all 29 patients and various edemas, it was found that for 125I seed implants, if the postimplant dose evaluation is performed based on image scans taken between 5 and 9 weeks, the average error will be less than 5%, with a maximum possible error less than 10% in 80% coverage dose; for 103Pd seed implants, if the postimplant dose evaluation is performed based on image scans taken between 2 and 4 weeks, the average error will be less than 5%, with a maximum error less than 15% in 80% coverage dose. Because of edema, a conventional preimplant plan also overestimates dose coverage of prostate. On the average, a standard preimplant planning overestimates dose coverage by about 6% for 125I implants and 14% for 103Pd implants in our study. CONCLUSION: Based on the dynamic model, the optimum timing of image scans for postimplant dose evaluation of prostate seed implantation is 7 weeks postimplantation for 125I implants and about 3 weeks for 103Pd implants. (ABSTRACT TRUNCATED)

Brachytherapy↗
PubMed1999

American Brachytherapy Society (ABS) recommendations for transperineal permanent brachytherapy of prostate cancer.

PURPOSE/OBJECTIVE: To develop and disseminate the American Brachytherapy Society (ABS) recommendations for the clinical quality assurance and guidelines of permanent transperineal prostate brachytherapy with 125I or 103Pd. METHODS AND MATERIALS: The ABS formed a committee of experts in prostate brachytherapy to develop consensus guidelines through a critical analysis of published data supplemented by their clinical experience. The recommendations of the panels were reviewed and approved by the Board of Directors of the ABS. RESULTS: Patients with high probability of organ-confined disease are appropriately treated with brachytherapy alone. Brachytherapy candidates with a significant risk of extraprostatic extension should be treated with supplemental external beam radiation therapy (EBRT). Patient selection guidelines were developed. Dosimetric planning of the implant should be carried out for all patients before seed insertion. A modified peripheral loading is preferred. The AAPM TG-43 recommendations requiring a change in prescription dose for 125I sources should be universally implemented. The recommended prescription doses for monotherapy are 145 Gy for 125I and 115-120 Gy for 103Pd. The corresponding boost doses (after 40-50 Gy EBRT) are 100-110 Gy and 80-90 Gy, respectively. Clinical evidence to guide selection of radionuclide (103Pd or 125I) is lacking. Post implant dosimetry and evaluation must be performed on all patients. It is suggested that the dose that covers 90% (D90) and 100% (D100) of the prostate volume and the percentage of the prostate volume receiving the prescribed dose (V100) be obtained from a dose-volume histogram (DVH) and reported. CONCLUSION: Guidelines for appropriate patient selection, dose reporting, and improved quality of permanent prostate brachytherapy are presented. These broad recommendations are intended to be technical and advisory in nature, but the ultimate responsibility for the medical decisions rests with the treating physician. This is a constantly evolving field, and the recommendations are subject to modifications as new data becomes available.

Biopsy↗
PubMed1999

A dynamic model for the estimation of optimum timing of computed tomography scan for dose evaluation of 125I or 103Pd seed implant of prostate.

PURPOSE/OBJECTIVE: The dosimetric evaluation of permanent 125I or 103Pd prostate implant is based on the assumption that both prostate and seeds are static throughout the entire treatment time which lasts months. However, the prostate is often edematous after the surgical implantation of seeds. Therefore, both the volume of the prostate and the seed locations change dynamically as the edema resolves. This effect has impact on the validity of postimplant analysis based upon a CT scan. If a CT scan is taken too early after implantation while there is edema in the prostate, the dose delivered by the implant may be underestimated. If the imaging is delayed too long, the dose may be overestimated. The magnitude of this effect depends on both of the half-life of the isotope used and the half-life and magnitude of the edema. This study describes a dynamic biomathematical model which takes edema into account in calculating the dose delivered by the implant and is used to investigate the optimum time to obtain the postimplant CT scan. MATERIALS AND METHODS: The dynamic biomathematical model is a numerical integration of the accumulated dose in which the prostate dimensions, the seed locations, and the source strength are all functions of time. The function which describes the change in prostate dimensions and seed locations as a function of time was determined in a separate study by analysis of serial postimplant CT scans. Dose-volume histograms (DVH) of the prostate for the total dose generated by the dynamic model are compared to DVHs generated by CT scans simulated for postimplant intervals ranging from 0 to 300 days after the implantation for 30 different combinations of the magnitude and duration of edema. RESULTS: DVHs of the prostate calculated by taking edema into account show that the time of obtaining a CT scan for postimplant analysis is critical to the accuracy of dose evaluations. The comparison of the DVHs generated by the dynamic model to those generated by the CT scans simulated for a range of postimplant intervals show that obtaining the CT scan too early tends to underestimate the total dose while obtaining the CT scan after the edema is resolved tends to overestimate it. The results show that the optimum timing of the CT scan depends upon the duration of the edema and the half-life of the radioisotope used. It is almost independent of the magnitude of the edema. Thus, a unique optimum time window for the imaging study cannot be defined for either 125I or 103Pd implants. However, an optimum time window can be identified for which the calculated dose, on the average, will generally differ from the actual dose by less than 5%, with a maximum error not exceeding 15%. Such a window is 4 to 10 weeks after the implantation for an 125I implant, and 2 to 4 weeks for a 103Pd implant. CONCLUSIONS: A dynamic biomathematical model to correct for the effects of edema in calculating the total dose delivered by an 125I or 103Pd seed implant has been developed. The model has been used to investigate the optimum time window during which the postimplant CT scans for analysis should be obtained.

Brachytherapy↗
PubMed1999

A minimax entropy registration framework for patient setup verification in radiotherapy.

In external beam radiotherapy (EBRT), patient setup verification over the entire course of fractionated treatment is necessary for accurate delivery of a specified dose to the tumor. We are working on the development of a minimax entropy registration framework for patient setup verification using dual portal images and the treatment planning 3D CT dataset. In this paper, we present an overview of our registration framework, where an iteratively and automatically estimated segmentation of the portal image is utilized to more accurately and robustly register the portal image to the 3D treatment-planning CT data. In addition, we describe initial testing of this approach. We note that, due to low resolution and low contrast of the portal images, this registration presents a difficult problem. We also note that the registration of the images in our proposed method is guided by the bony structure visible in the portal and the 3D CT images. However, since the prostate can move with respect to the pelvic bone, we propose using ultrasound images to quantify this movement.

Algorithms↗
PubMed1999

Long-term complications with prostate implants: iodine-125 vs. palladium-103.

The linear quadratic model predicts that the normal tissue biologically effective dose (BED) will be lower with palladium-103 (Pd-103) vs. iodine-125 (I-125) for the currently prescribed minimum tumor doses (MTD) used for I-125 (160 Gy) and Pd-103 (115 Gy) prostate cancer brachytherapy. The predicted BEDs for I-125 and Pd-103 suggest that the long-term complication rates should be lower with Pd-103 vs. I-125 in clinical practice. A review of 123 early stage T1c and T2 prostate cancer patients implanted at Yale University with I-125 (82 patients) or Pd-103 (41 patients) reveals a significantly lower overall complication rate with Pd-103 (0%) vs. I-125 (13%). Most important, the grade III-IV complication rate for Pd-103 was 0% vs. 6% for I-125. The 3-year actuarial probability of remaining free of a long-term complication was 100% for Pd-103 vs. 82% for I-125 (P<0.01). A review of the literature for 992 patients implanted with I-125 vs. 540 patients implanted with Pd-103 shows a consistently higher complication rate for I-125 vs. Pd-103. Assuming that the MTD for Pd-103 may be increased to produce an equivalent late-reacting normal tissue BED to that for I-125, then the radiobiology model predicts the log10 cell kill for Pd-103 implant will be greater than that of an I-125 implant for all tumor doubling times (high-grade tumors and low-grade tumors). The implications of these findings are discussed in terms of future research directions for prostate implants.

Actuarial Analysis↗
PubMed1999

Comparison of preservative-free bupivacaine vs. lidocaine for intracameral anesthesia: a randomized clinical trial and in vitro analysis.

PURPOSE: To determine whether intracameral bupivacaine hydrochloride 0.5% is as effective as lidocaine hydrochloride 1.0% in controlling discomfort of patients during phacoemulsification and posterior chamber intraocular lens implantation. In rabbits, corneal endothelial cell function, ultrastructure, and viability were evaluated after in vitro perfusion of bupivacaine 0.5%. METHODS: In a double-masked, controlled trial, 48 eyes of 48 patients with uncomplicated age-related cataract were randomly assigned to receive bupivacaine 0.5% or lidocaine 1.0% intracamerally before phacoemulsification with a posterior chamber intraocular lens. Outcome measures such as pain, visual acuity, amount of sedation, length of surgery, pupil size, intraocular pressure, corneal clarity, and anterior chamber reaction were compared. In laboratory studies, paired rabbit corneas were evaluated by endothelial cell perfusion with either bupivacaine 0.5%, bupivacaine 0.5% and glutathione bicarbonate Ringer solution in a 1:1 ratio or bupivacaine 0.5% buffered to a pH of 7.0. The paired control corneas were perfused with glutathione bicarbonate Ringer solution and rates of corneal swelling were determined. Cell ultrastructure and viability were also evaluated. RESULTS: In the randomized trial, there was no significant difference in the pain patients had during surgery or in the early or late postoperative period. No statistically significant difference was seen between the two groups in terms of pupil size, intraocular pressure, corneal edema, anterior chamber reaction, or visual acuity immediately after the operation or on postoperative day 1. Paired rabbit corneas perfused with bupivacaine 0.5% and bupivacaine 0.5% buffered to a pH of 7.0 swelled significantly (P<.001, P = .009, respectively), and had corneal endothelial cell damage. Dilution of the bupivacaine 1:1 with glutathione bicarbonate Ringer solution prevented corneal edema and damage to the corneal endothelium. Endothelial cell viability was also decreased after perfusion of bupivacaine 0.5% (P<.001). CONCLUSIONS: Clinically, bupivacaine 0.5% is as effective as lidocaine 1.0% for anesthesia during phacoemulsification and posterior chamber intraocular lens implantation. However, in vitro perfusion of bupivacaine 0.5% damaged the corneal endothelium of rabbits except when the drug was diluted 1:1 with glutathione bicarbonate Ringer solution. Surgeons who use 0.2 to 0.5 ml of intracameral bupivacaine 0.5% should be aware of its potential to cause endothelial cell damage because of its lipid solubility. The bupivacaine 0.5% should be diluted at least 1:1 with balanced salt solution before intracameral injection, followed immediately by phacoemulsification. The surgeon should ensure that the bupivacaine 0.5% is nonpreserved and packaged in single-use vials or flip-top containers.

Aged↗
PubMed1999

Calpain activity in bone marrow transplant-associated thrombotic thrombocytopenic purpura.

The pathophysiology of thrombotic thrombocytopenic purpura (TTP) is not well understood. Recent studies have described a platelet aggregating factor which has been characterized as a calcium-dependent cysteine protease (calpain) in patients with TTP. A type of TTP, sometimes called secondary TTP, has been associated with bone marrow transplantation (BMT). However, unlike primary adult TTP, BMT-TTP has important differences and often does not respond well to plasma exchange. We describe the measurement of calpain activity in a group of BMT patients (with and without the clinical syndrome of transplant-associated TTP). Calpain was measured using a functional assay (14C-serotonin platelet release with inhibition by the cysteine protease inhibitor, leupeptin) in the sera of patients following autologous (auto) or allogeneic (allo) BMT. We also independently diagnosed and graded the BMT-TTP on the day of blood sampling using a scale that related to the percentage schistocytes and lactic dehydrogenase level. Calpain activity was detected in 1/8 (13%) grade 0-1 (6 auto, 2 allo); 6/16 (38%) grade 2 (3 auto, 13 allo) 9/16 (56%) grade 3 (2 auto, 14 allo) and 8/8 (100%) grade 4 BMT-TTP. Pre-BMT samples were tested in 10 allo-BMT patients who had positive calpain results post-BMT. One patient gave positive results before the transplant. This patient developed grade 4 BMT-TTP (day 24 post-BMT) and died despite apheresis. Positive calpain results were highly associated with neurologic symptoms, P < 0.001. Nineteen of 24 (79%) patients with positive results had neurologic symptoms compared to three of 21 (14%) patients with negative results. In conclusion, calpain was detected in half of the BMT patients with mild to moderate BMT-TTP (grades 2-3) and was uniformly found in those with severe (grade 4) BMT-TTP. Typically the calpain activity develops as TTP complicates the transplant process. It is unknown whether calpain contributes to the pathogenesis of this disorder, or is a secondary event.

Adult↗
PubMed1999

Intravascular brachytherapy physics: report of the AAPM Radiation Therapy Committee Task Group no. 60. American Association of Physicists in Medicine.

Recent preclinical and clinical studies indicate that irradiation using ionizing radiation in the dose range of 15 to 30 Gy may reduce the occurrence of restenosis in patients who have undergone an angioplasty. Several delivery systems of intravascular brachytherapy have been developed to deliver radiation doses in this range with minimal normal tissue toxicity. In late 1995 the American Association of Physicists in Medicine (AAPM) formed a task group to investigate these issues and to report the current state of the art of intravascular brachytherapy physics. The report of this task group is presented here.

Angioplasty, Balloon, Coronary↗