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R Nath

Publications and source records attributed to R Nath.

At least 73 records · Page 4Linked to original sources
PubMed1999

Combined use of transverse and scout computed tomography scans to localize radioactive seeds in an interstitial brachytherapy implant.

Various techniques have been developed to localize radioactive sources in brachytherapy implants. The most common methods include the orthogonal film method, the stereo-shift film method, and recently, direct localization from a series of contiguous CT transverse images. The major advantage of the CT method is that it provides the seed locations relative to anatomic structures. However, it is often the case that accurate identification and localization of the sources become difficult because of partial source artifacts in more than one transverse cut and other artifacts on CT images. A new algorithm has been developed to combine the advantages of using a pair of orthogonal scout views with the advantages of using a stack of transverse cuts. In the new algorithm, a common reference point is used to correlate CT transverse images and two orthogonal scout CT scans (AP and lateral). The radioactive sources are localized on CT transverse images. At the same time, the sources are displayed automatically on the two CT scout scans. In this way, the individual sources can be clearly distinguished and ambiguities arising from partial source artifacts are resolved immediately. Because of the finite slice thickness of transverse cuts, the longitudinal coordinates are more accurately obtained from the scout views. Therefore, the longitudinal coordinates of seeds localized on the transverse cuts are adjusted so that they match the position of the seeds on scout views. The algorithm has been tested on clinical cases and has proved to be a time saving and accurate method.

Adult↗
PubMed1999

Guidance to users of Nycomed Amersham and North American Scientific, Inc., I-125 interstitial sources: dosimetry and calibration changes: recommendations of the American Association of Physicists in Medicine Radiation Therapy Committee Ad Hoc Subcommittee on Low-Energy Seed Dosimetry.

Dose calculations to patients undergoing implantation of 125I interstitial brachytherapy sources are affected by two recent changes in low-energy seed dosimetry: (a) implantation of a new primary air-kerma strength standard at the National Institute of Standards and Technology (NIST) on 1 January 1999 and (b) publication of revised dose-rate distributions in AAPM's Task Group 43 Report. The guidance herein represents AAPM's recommendations for users of 125I interstitial seed products marketed prior to 1 January 1999 (Nycomed Amersham models 6711 and 6702 and North American Scientific, Inc. models 3631 A/S and 3631 A/M. Implementation of Task Group 43 (TG43) 125I dose calculations involves revising data stored in files of radiation treatment planning software and lowering the prescribed dose to be delivered to patients by as much as 15% to avoid modifying the dose actually delivered to patients. The magnitude of the dose prescription change depends on the dosimetry data used prior to TG43 and the implant geometry. Adapting to the revised NIST calibration standard requires the user to increase the dose-rate constant (or its equivalent by 11.5%) but does not require modification of the prescribed dose. Failure to correctly implement these modifications can result in 20% or even 30% errors.

Brachytherapy↗
PubMed1999

The impact of edema on planning 125I and 103Pd prostate implants.

Permanent transperineal interstitial 125I and 103Pd prostate implants are generally planned to deliver a specific dose to a clinically defined target volume; however, the post-implant evaluation usually reveals that the implant delivered a lower or higher dose than planned. This difference is generally attributed to such factors as source placement errors, overestimation of the prostate volume on CT, and post-implant edema. In the present work we investigate the impact of edema alone. In routine prostate implant planning, it is customary to assume that both the prostate and seeds are static throughout the entire treatment time, and post-implant edema is not taken into consideration in the dosimetry calculation. However, prostate becomes edematous after seed implantation, typically by 50% in volume [Int. J. Radiat. Oncol., Biol., Phys. 41, 1069-1077 (1998)]. The edema resolves itself exponentially with a typical half-life of 10 days. In this work, the impact of the edema-induced dynamic change in prostate volume and seed location on the dose coverage of the prostate is investigated. The total dose delivered to the prostate was calculated by use of a dynamic model, which takes edema into account. In the model, the edema resolves exponentially with time, as reported in a separate study based on serial CT scans [Int. J. Radiat. Oncol., Biol., Phys. 41, 1069-1077 (1998)]. The model assumes that the seeds were implanted exactly as planned, thus eliminating the effect of source placement errors. Implants based on the same transrectal ultrasound (TRUS) images were planned using both 125I and 103Pd sources separately. The preimplant volume and planned seed locations were expanded to different degrees of edema to simulate the postimplant edematous prostate on day 0. The model calculated the dose in increments of 24 h, appropriately adjusting the prostate volume, seed locations, and source strength prior to each time interval and compiled dose-volume histograms (DVH) of the total dose delivered. A total of 30 such DVHs were generated for each implant using different combinations of edema half-life and magnitude. In addition, a DVH of the plan was compiled in the conventional manner, assuming that the prostate volume and seeds were static during treatment. A comparison of the DVH of the static model to the 30 edema corrected DVHs revealed that the plan overestimated the total dose by an amount that increased with the magnitude of the edema and the edema half-life. The maximum overestimation was 15% for 125I and 32% for 103Pd. For more typical edema parameters (a 50% increase in volume and a 10 day half-life) the static plan for 125I overestimated the total dose by about 5%, whereas that for 103Pd overestimated it by about 12%.

Brachytherapy↗
PubMed1999

AAPM's TG-51 protocol for clinical reference dosimetry of high-energy photon and electron beams.

A protocol is prescribed for clinical reference dosimetry of external beam radiation therapy using photon beams with nominal energies between 60Co and 50 MV and electron beams with nominal energies between 4 and 50 MeV. The protocol was written by Task Group 51 (TG-51) of the Radiation Therapy Committee of the American Association of Physicists in Medicine (AAPM) and has been formally approved by the AAPM for clinical use. The protocol uses ion chambers with absorbed-dose-to-water calibration factors, N(60Co)D,w which are traceable to national primary standards, and the equation D(Q)w = MkQN(60Co)D,w where Q is the beam quality of the clinical beam, D(Q)w is the absorbed dose to water at the point of measurement of the ion chamber placed under reference conditions, M is the fully corrected ion chamber reading, and kQ is the quality conversion factor which converts the calibration factor for a 60Co beam to that for a beam of quality Q. Values of kQ are presented as a function of Q for many ion chambers. The value of M is given by M = PionP(TP)PelecPpolMraw, where Mraw is the raw, uncorrected ion chamber reading and Pion corrects for ion recombination, P(TP) for temperature and pressure variations, Pelec for inaccuracy of the electrometer if calibrated separately, and Ppol for chamber polarity effects. Beam quality, Q, is specified (i) for photon beams, by %dd(10)x, the photon component of the percentage depth dose at 10 cm depth for a field size of 10x10 cm2 on the surface of a phantom at an SSD of 100 cm and (ii) for electron beams, by R50, the depth at which the absorbed-dose falls to 50% of the maximum dose in a beam with field size > or =10x10 cm2 on the surface of the phantom (> or =20x20 cm2 for R50>8.5 cm) at an SSD of 100 cm. R50 is determined directly from the measured value of I50, the depth at which the ionization falls to 50% of its maximum value. All clinical reference dosimetry is performed in a water phantom. The reference depth for calibration purposes is 10 cm for photon beams and 0.6R50-0.1 cm for electron beams. For photon beams clinical reference dosimetry is performed in either an SSD or SAD setup with a 10x10 cm2 field size defined on the phantom surface for an SSD setup or at the depth of the detector for an SAD setup. For electron beams clinical reference dosimetry is performed with a field size of > or =10x10 cm2 (> or =20x20 cm2 for R50>8.5 cm) at an SSD between 90 and 110 cm. This protocol represents a major simplification compared to the AAPM's TG-21 protocol in the sense that large tables of stopping-power ratios and mass-energy absorption coefficients are not needed and the user does not need to calculate any theoretical dosimetry factors. Worksheets for various situations are presented along with a list of equipment required.

Biophysical Phenomena↗
PubMed1999

Permanent prostate seed implant brachytherapy: report of the American Association of Physicists in Medicine Task Group No. 64.

There is now considerable evidence to suggest that technical innovations, 3D image-based planning, template guidance, computerized dosimetry analysis and improved quality assurance practice have converged in synergy in modern prostate brachytherapy, which promise to lead to increased tumor control and decreased toxicity. A substantial part of the medical physicist's contribution to this multi-disciplinary modality has a direct impact on the factors that may singly or jointly determine the treatment outcome. It is therefore of paramount importance for the medical physics community to establish a uniform standard of practice for prostate brachytherapy physics, so that the therapeutic potential of the modality can be maximally and consistently realized in the wider healthcare community. A recent survey in the U.S. for prostate brachytherapy revealed alarming variance in the pattern of practice in physics and dosimetry, particularly in regard to dose calculation, seed assay and time/method of postimplant imaging. Because of the large number of start-up programs at this time, it is essential that the roles and responsibilities of the medical physicist be clearly defined, consistent with the pivotal nature of the clinical physics component in assuring the ultimate success of prostate brachytherapy. It was against this background that the Radiation Therapy Committee of the American Association of Physicists in Medicine formed Task Group No. 64, which was charged (1) to review the current techniques in prostate seed implant brachytherapy, (2) to summarize the present knowledge in treatment planning, dose specification and reporting, (3) to recommend practical guidelines for the clinical medical physicist, and (4) to identify issues for future investigation.

Brachytherapy↗
PubMed1999

Granulocyte-colony stimulating factor (G-CSF)-primed, delayed marrow harvests as a source of hematopoietic stem and progenitor cells for allogeneic transplantation.

We evaluated the ability of G-CSF to increase the number of hematopoietic stem cells obtained by "delayed" BM harvest for allogeneic transplantation. Five normal donors received G-CSF @ 10 mcg/kg/day x 5 followed by repeat PB and BM assays at day 6 and 16, and BM harvest at day 16. Stem cells were not increased in the BM at day 16. Five patients underwent BMT and engrafted at +10 to +19 days. While the tested strategy offers no intrinsic advantages, its potential cannot be evaluated fully without alternative timing and/or additional, "early acting" growth factors.

Blood Donors↗
PubMed1999

Anterior segment anomalies of the eye associated with multiple skeletal abnormalities and early lethality: confirmation of an autosomal recessive syndrome.

We report two sibs from a complexly consanguineous family with joint contractures, skeletal abnormalities, anterior segment anomalies of the eye and early lethality. The features of these sibs are similar to the features of the sibs reported by Al-Gazali et al. (Clin Dysmorphol 3: 238-244, 1994). This report confirms the identity of this new autosomal recessive syndrome.

Abnormalities, Multiple↗
PubMed1999

Recurrence of the severe form of microgastria-limb reduction defect in a consanguineous family.

This report concerns two sibs from a consanguineous Sudanese family with microgastria-limb reduction defect associated with hydrocephalus and agenesis of corpus callosum. We suggest that these cases together with other previously reported cases of central nervous system (CNS) anomalies associated with microgastria-limb reduction defect could represent an autosomal recessive syndrome differing from the classical microgastria-limb reduction defect by its severity, presence of CNS anomalies and its pattern of inheritance.

Abnormalities, Multiple↗
PubMed1998

Simultaneous degradation of alphaII- and betaII-spectrin by caspase 3 (CPP32) in apoptotic cells.

The degradation of alphaII- and betaII-spectrin during apoptosis in cultured human neuroblastoma SH-SY5Y cells was investigated. Immunofluorescent staining showed that the collapse of the cortical spectrin cytoskeleton is an early event following staurosporine challenge. This collapse correlated with the generation of a series of prominent spectrin breakdown products (BDPs) derived from both alphaII- and betaII-subunits. Major C-terminal alphaII-spectrin BDPs were detected at approximately 150, 145, and 120 kDa (alphaII-BDP150, alphaII-BDP145, and alphaII-BDP120, respectively); major C-terminal betaII-spectrin BDPs were at approximately 110 and 85 kDa (betaII-BDP110 and betaII-BDP85, respectively). N-terminal sequencing of the major fragments produced in vitro by caspase 3 revealed that alphaII-BDP150 and alphaII-BDP120 were generated by cleavages at DETD1185*S1186 and DSLD1478*S1479, respectively. For betaII-spectrin, a major caspase site was detected at DEVD1457*S1458, and both betaII-BDP110 and betaII-BDP85 shared a common N-terminal sequence starting with Ser1458. An additional cleavage site near the C terminus, at ETVD2146*S2147, was found to account for betaII-BDP85. Studies using specific caspase or calpain inhibitors indicate that the pattern of spectrin breakdown during apoptosis differs from that during non-apoptotic cell death. We postulate that in concert with calpain, caspase rapidly targets critical sites in both alphaII- and betaII-spectrin and thereby initiates a rapid dissolution of the spectrin-actin cortical cytoskeleton with apoptosis.

Amino Acid Sequence↗
PubMed1998

Caspase-mediated fragmentation of calpain inhibitor protein calpastatin during apoptosis.

Two cysteine protease families (caspase and calpain) participate in apoptosis. Here we report that the endogenous calpain inhibitor calpastatin is fragmented by caspase(s) to various extents during early apoptosis in two cell types. In anti-fas or staurosporine-treated Jurkat T-cells, the high-molecular-weight form (HMW) of calpastatin (apparent Mr 110 K) was extensively degraded to immunoreactive fragments of Mr 75 K and 30 K In apoptotic SH-SY5Y human neuroblastoma cells, HMW calpastatin was degraded to a major immunoreactive fragment of 75 K. In both cell types, fragmentation of HMW calpastatin was blocked by a caspase-specific inhibitor carbobenzoxy-Asp-CH2OC(O)-2,6-dichlorobenzene. In vitro translated HMW calpastatin was sensitive to proteolysis by recombinant caspase-1, -3, and -7. By contrast, in vitro translated LMW calpastatin (which lacks domains L and I) was cleaved into multiple fragments only by caspase-1 and was relatively resistant to caspase-3, -7, and other caspases tested. Consistently with that, purified erythroid LMW calpastatin was also highly susceptible to caspase-1 digestion. Recombinant human calpastatin spanning domain I through III (CAST(DI-III)) was found cleaved by caspase-1 at at least three sites, located in either the A or the C helix of domains I and III (ALDD137*L, LSSD203*F and ALAD404*S), while only a single site (ALDD137*L) was cleaved by caspase-3. These findings suggest that both HMW and LMW calpastatins are more vulnerable to caspase-1 than to caspase-3. Surprisingly, both erythroid LMW calpastatin and recombinant CAST(DI-III) fragmented by caspase-1 suffered only a less than twofold reduction of inhibitory activity toward calpain. We propose that the proteolysis of calpastatin in early apoptosis might have yet unidentified effects on the cross-talk between the two protease systems.

Apoptosis↗
PubMed1998

Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population.

Hepatic veno-occlusive disease (VOD) is the most common of the regimen-related toxicities accompanying stem cell transplantation (SCT). Despite aggressive therapies, including the combination of tissue plasminogen activator (t-PA) and heparin, severe VOD is almost uniformly fatal. Defibrotide (DF) is a polydeoxyribonucleotide with activity in several vascular disorders and, unlike t-PA and heparin, produces no systemic anticoagulant effects. Nineteen patients who developed severe VOD after SCT were treated with DF on a compassionate-use basis. Patients had clinically established VOD and met risk criteria predicting progression and fatality. At the initiation of DF, all 19 patients had evidence of multiorgan dysfunction; median bilirubin was 22.3 mg/dL, 12 patients had renal insufficiency (5 dialysis dependent), 14 required oxygen supplementation, and encephalopathy was present in 8 patients. Beginning a median of 6 days after diagnosis of VOD, DF was administered intravenously in doses ranging from 5 to 60 mg/kg/d for a planned minimum course of 14 days. In no case was DF discontinued for attributable toxicity. No severe hemorrhage related to DF administration was observed. Resolution of VOD (bilirubin <2 mg/dL with improvement in other symptoms and signs) was seen in 8 patients (42%). Six of 8 responders survived past day +100, contrasted with the 2% predicted survival reported in comparable patients. The observed response rate, survival to day +100, and absence of significant DF treatment-associated toxicity are compelling and warrant further evaluation.

Adolescent↗
PubMed1998

In vivo neutron dosimetry during high-energy Bremsstrahlung radiotherapy.

PURPOSE: A new technique is presented for in vivo measurements of the dose equivalent from photoneutrons produced by high-energy radiotherapy accelerators. METHODS AND MATERIALS: The dosimeters used for this purpose are vials of superheated halocarbon droplets suspended in a tissue-equivalent gel. Neutron interactions nucleate the formation of bubbles, which can be recorded through the volume of gel they displace from the detector vials into graduated pipettes. These detectors offer inherent photon discrimination, dose-equivalent response to neutrons, passive operation, and small sensitive size. An in vivo vaginal probe was fabricated containing one of these neutron detector vials and a photon-sensitive diode. Measurements were carried out in patients undergoing high-energy x-ray radiotherapy and were also repeated in-phantom, under similar irradiation geometries. RESULTS AND CONCLUSION: Neutron doses of 0.02 Sv were measured in correspondence to the cervix, 50 cm from the photon beam axis, following a complete treatment course of 46.5 Gy with an upper mantle field of 18-MV x-rays. This fraction of dose from neutrons is measured reliably within an intense photon background, making the technique a valid solution to challenging dosimetry problems such as the determination of fetal exposure in radiotherapy. These measurements can be easily carried out with tissue-equivalent phantoms, as our results indicate an excellent correlation between in vivo and in-phantom dosimetry.

Aged↗
PubMed1998

2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease.

A series of 2-amino-4H-3,1-benzoxazin-4-ones have been synthesized and evaluated as inhibitors of the complement enzyme C1r. C1r is a serine protease at the beginning of the complement cascade, and complement activation by beta-amyloid may represent a major contributing pathway to the neuropathology of Alzheimer's disease. Compounds such as 7-chloro-2-[(2-iodophenyl)-amino]benz[d][1,3]oxazin-4-one (32) and 7-methyl-2-[(2-iodophenyl)amino]benz[d][1,3]oxazin-4-one (37) show improved potency compared to the reference compound FUT-175. Many of these active compounds also possess increased selectivity for C1r compared to trypsin and enhanced hydrolytic stability relative to 2-(2-iodophenyl)-4H-3,1-benzoxazin-4-one (1).

Complement C1r↗
PubMed1998

Review of AAPM Task Group No. 43 recommendations on interstitial brachytherapy sources dosimetry. American Association of Physicists in Medicine.

In 1995, the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) published its recommendations on the dosimetry of interstitial brachytherapy sources. The report recommended the use of a new dose calculation formalism based on measured quantities. The formalism in modular form permits the computation of doses in two dimensions for 103Pd, 125I, and 192Ir sources. The TG-43 dose calculation formalism introduced new and updated quantities such as air kerma strength, dose rate constant, radial dose function, anisotropy function and anisotropy factor. The dose rate obtained using the TG-43 dose calculation formalism and updated source dosimetry data can be expected to be different from some of the currently used systems by as much as 17%. For the same treatment and implementing the TG-43 dosimetry with point source approximation, the widely prescribed dose of 160 Gy for 125I permanent implants using model 6711 sources changes to 144 Gy. In addition to the dose calculation formalism, TG-43 report also stated that the air kerma strength provided by NIST is estimated to be approximately 7-10% higher than it should be, due to low energy photon contamination for 125I. This difference has not been accounted for in the TG-43 report.

Brachytherapy↗
PubMed1998

Evidence for activation of caspase-3-like protease in excitotoxin- and hypoxia/hypoglycemia-injured neurons.

Caspase activation has been shown to be a critical step in several models of neuronal apoptosis such as staurosporine treatment of human neuroblastoma SH-SY5Y cells and potassium deprivation of rat cerebellar granule neurons. One common event is the appearance of caspase-mediated 120-kDa nonerythroid alpha-spectrin breakdown product (SBDP120). Second, inhibitors of the caspase family are effective blockers of such neuronal death. In this study, we report the appearance of caspase-mediated SBDP120 in excitotoxin-challenged fetal rat cerebrocortical neurons [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate] and rat cerebellar granule neurons (NMDA and kainate). A general caspase inhibitor, carbobenzoxy-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-D-DCB), blocked the formation of SBDP120 under these conditions and attenuated the observed NMDA-induced lactate dehydrogenase (LDH) release in both cell types. Furthermore, hydrolytic activity toward a caspase-3-preferred synthetic peptide substrate, acetyl-DEVD-7-amido-4-methylcoumarin, was significantly elevated in NMDA-treated granule neurons. Lastly, oxygen-glucose deprivation (OGD)-challenged cerebrocortical cultures also showed the appearance of SBDP120. Again, Z-D-DCB blocked the SBDP120 formation as well as attenuated the LDH release from the OGD-challenged neurons. Taken together, the presence of caspase-specific SBDP120 and the neuroprotective effects of Z-D-DCB strongly suggest that caspase activation contributes at least in part to excitotoxin- and OGD-induced neuronal death.

Animals↗