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Biomedical subjects

R Nath

Publications and source records attributed to R Nath.

At least 37 records · Page 2Linked to original sources
PubMed2001

Depth dose-equivalent and effective energies of photoneutrons generated by 6-18 MV X-ray beams for radiotherapy.

Photoneutron production was investigated on Siemens KD 2 and Varian Clinac accelerators operating in the 6-18 MV range. Neutron dose equivalent rates were measured on the surface of a water phantom at the isocenter of the accelerators and also inside the phantom at depths of 1, 5, and 10 cm and off-axis distances of 0, 20, and 50 cm. Superheated drop detectors based on dichlorofluoromethane and etched-track detectors with boronated converters were employed in this study. The energy response of these detectors permits a direct measurement of dose equivalent without prior knowledge of the neutron energy spectra. Dose equivalent rates were assessed using the Q(L) relationship from ICRP publication 60, as well as using earlier data from ICRP publication 21. This permitted both a comparison with previously published data and an assessment of the impact of the recent ICRP recommendations--which were found to increase the dose equivalent levels by about 30%. In addition, the depth corresponding to 50% of maximum dose equivalent, dH50, was determined along the central axis of the beams and at 50 cm off-axis. Monte Carlo neutron transport calculations were performed to determine the depth-dose equivalent distributions in a phantom irradiated with monoenergetic neutrons. Effective energies of the photoneutron spectra were then estimated by comparing our measured dH50 values to those calculated for monoenergetic neutrons. It was found that the effective photoneutron energy is 1.8-2.1 MeV within the 10-18 MV x-ray beams, and it is 0.5-0.8 MeV for photoneutrons transmitted through the accelerator head. Data from this work cover most of the x-ray beam energies in clinical use and permit an assessment of integral dose values as well as specific organ doses to a radiotherapy patient.

Humans↗
PubMed2001

Bilateral nerve graft during radical retropubic prostatectomy: 1-year followup.

PURPOSE: With the interposition of a sural nerve graft to replace resected cavernous nerves at radical retropubic prostatectomy, we have previously reported the return of effective erectile function. We determine the efficacy of this procedure in a series of men with at least 1-year followup. MATERIALS AND METHODS: A total of 12 potent men (mean age plus or minus standard deviation 57 +/- 6 years) with clinically localized prostate cancer underwent radical retropubic prostatectomy, with deliberate wide bilateral neurovascular bundle resection and placement of bilateral nerve grafts. A series of patient and partner erectile dysfunction questionnaires, and patient interviews were performed at 3, 6, 12 and 18 months postoperatively. Only results for those men with a followup of 12 months or greater (mean 16 +/- 4) are presented. A control group of 12 men who had undergone bilateral nerve resection but declined nerve graft placement, was also followed. RESULTS: Of the 12 men 4 (33%) had spontaneous medically unassisted erections sufficient for sexual intercourse with vaginal penetration. An additional 5 (42%) men describe "40 to 60%" spontaneous erections, with fullness, no rigidity and not able to penetrate. Overall, 9 (75%) men had return of erectile activity. No demonstrable erections occurred before 5 months postoperatively. The greatest return of function was observed at 14 to 18 months after surgery. CONCLUSIONS: This surgical technique has minimal morbidity and represents a significant advance in prostate cancer surgery in men requiring bilateral nerve resection. Our study clearly demonstrates recovery of erectile function in men who underwent bilateral nerve graft placement during radical retropubic prostatectomy when both cavernous nerves were deliberately resected.

Aged↗
PubMed2001

Dose rate constant and energy spectrum of interstitial brachytherapy sources.

In the past two years, several new manufacturers have begun to market low-energy interstitial brachytherapy seeds containing 125I and 103Pd. Parallel to this development, the National Institute of Standards and Technology (NIST) has implemented a modification to the air-kerma strength (S(K)) standard for 125I seeds and has also established an S(K) standard for 103Pd seeds. These events have generated a considerable number of investigations on the determination of the dose rate constants (inverted V) of interstitial brachytherapy seeds. The aim of this work is to study the general properties underlying the determination of dose rate constant and to develop a simple method for a quick and accurate estimation of dose rate constant. As the dose rate constant of clinical seeds is defined at a fixed reference point, we postulated that dose rate constant may be calculated by treating the seed as an effective point source when the seed's source strength is specified in S(K) and its source characteristics are specified by the photon energy spectrum measured in air at the reference point. Using a semi-analytic approach, an analytic expression for dose rate constant was derived for point sources with known photon energy spectra. This approach enabled a systematic study of dose rate constant as a function of energy. Using the measured energy spectra, the calculated dose rate constant for 125I model 6711 and 6702 seeds and for 192Ir seed agreed with the AAPM recommended values within +/-1%. For the 103Pd model 200 seed, the agreement was 5% with a recently measured value (within the +/-7% experimental uncertainty) and was within 1% with the Monte Carlo simulations. The analytic expression for dose rate constant proposed here can be evaluated using a programmable calculator or a simple spreadsheet and it provides an efficient method for checking the measured dose rate constant for any interstitial brachytherapy seed once the energy spectrum of the seed is known.

Biophysical Phenomena↗
PubMed2001

AAPM protocol for 40-300 kV x-ray beam dosimetry in radiotherapy and radiobiology.

The American Association of Physicists in Medicine (AAPM) presents a new protocol, developed by the Radiation Therapy Committee Task Group 61, for reference dosimetry of low- and medium-energy x rays for radiotherapy and radiobiology (40 kV < or = tube potential < or = 300 kV). It is based on ionization chambers calibrated in air in terms of air kerma. If the point of interest is at or close to the surface, one unified approach over the entire energy range shall be used to determine absorbed dose to water at the surface of a water phantom based on an in-air measurement (the "in-air" method). If the point of interest is at a depth, an in-water measurement at a depth of 2 cm shall be used for tube potentials > or = 100 kV (the "in-phantom" method). The in-phantom method is not recommended for tube potentials < 100 kV. Guidelines are provided to determine the dose at other points in water and the dose at the surface of other biological materials of interest. The protocol is based on an up-to-date data set of basic dosimetry parameters, which produce consistent dose values for the two methods recommended. Estimates of uncertainties on the final dose values are also presented.

Air↗
PubMed2001

1,N(2)-propanodeoxyguanosine adduct formation in aortic DNA following inhalation of acrolein.

Recent reports indicate that many of the cytotoxic and health-threatening components of environmental tobacco smoke (ETS) reside in the vapor phase of the smoke. We have reported previously that inhalation of 1,3-butadiene, a prominent vapor phase component of ETS, accelerates arteriosclerotic plaque development in cockerels. In this study we asked whether inhaled acrolein, a reactive aldehyde that is also a prominent vapor-phase component of ETS, damages artery-wall DNA and accelerates plaque development. Cockerels inhaled 0, 1, or 10 ppm acrolein mixed with HEPA-filtered air for 6 hr. Half were killed immediately (day 1 group) for detection of the stable, premutagenic 1,N(2)-propanodeoxyguanosine acrolein adduct (AdG3) in aortic DNA via a (32)P-postlabeling/HPLC method, and half were killed after 10 days (day 10 group) for indirect assessment of adduct repair. In the day 1 group, acrolein-DNA adducts were 5 times higher in the 1 and 10 ppm groups than in HEPA-filtered air controls. However, in the day 10 group, adduct levels in the 1 and 10 ppm acrolein groups were reduced to the control adduct level. For the plaque studies, cockerels inhaled 1 ppm acrolein (6 hr/day, 8 weeks), mixed with the same HEPA-filtered air inhaled by controls. Plaque development was measured blind by computerized morphometry. Unlike butadiene inhalation, acrolein inhalation did not accelerate plaque development. Thus, even though repeated exposure to acrolein alone has no effect on plaque size under the exposure conditions described here, a single, brief inhalation exposure to acrolein elicits repairable DNA damage to the artery wall. These results suggest that frequent exposure to ETS may lead to persistent artery-wall DNA damage and thus provide sites on which other ETS plaque accelerants can act.

Acrolein↗
PubMed2001

Inhibition of p38 kinase mimics survival signal-linked protection against apoptosis in rat cerebellar granule neurons.

The mitogen-activated protein kinase (MAPK) cascades are thought to be important mediators in the transduction of extracellular signals into cellular responses. The p38 kinase, a member of the MAPK superfamily, is activated by a wide variety of extracellular stimuli and has been implicated in neuronal apoptosis induced by glutamate. In this study we have examined the role of p38 kinase in the potassium deprivation model of apoptosis in rat cerebellar granule neurons (CGN). An increase in p38 kinase activity was observed with a 15-minute potassium deprivation when compared to the basal level. We also found that SB203580 and PD169316, specific p38 kinase inhibitors, significantly attenuated apoptosis in potassium-deprived cells in a dose dependent manner. A decrease in caspase-3 mediated DEVD-MCA, substrate hydrolysis and the appearance of the 120 kDa-spectrin breakdown product in cells treated with SB203580 further suggests that the p38 kinase acts upstream of caspase-3 in the apoptosis cascade. The data provides evidence for an essential role of p38 kinase in mediating apoptotic cell death in CGN and the inhibition of p38 kinase mimics the suppression of apoptosis provided by natural survival signals.

Animals↗
PubMed2000

Metallothioneins, oxidative stress and the cardiovascular system.

Metallothioneins (MTs) discovered four decades ago as metal binding low molecular weight thiol proteins, in recent years, have generated immense interest due to their involvement in various physiological and pathophysiological events. In spite of the recent advances in the knowledge base in MTs, no specific study on the isolation or characterization of MTs isoforms and their precise function in the heart has been conducted. Although most stress conditions in the heart do not produce much change in myocardial MTs, TNF-alpha and IL-6 do induce MT in the heart to the extent comparable with the liver. Cardiotoxicity of anticancer drugs and vulnerability of the heart to other oxidative stress conditions may partially be due to lack of inducibility of MT in the heart by these interventions. A clear understanding of induction of MTs in the heart may help in the development of better approaches to modulate the pathogenesis of cardiomyopathies and heart failure.

Animals↗
PubMed2000

Processing of cdk5 activator p35 to its truncated form (p25) by calpain in acutely injured neuronal cells.

Recently, it was shown that conversion of cdk5 activator protein p35 to a C-terminal fragment p25 promotes a deregulation of cdk5 activity, which may contribute to neurodegeneration in Alzheimer's disease. In this study, we present evidence that calpain is a protease involved in the conversion of p35 to p25. To activate calpain, rat cerebellar granule neurons were treated with maitotoxin (MTX). A C-terminus-directed anti-p35 antibody detected that p35 conversion to p25 paralleled the formation of calpain-generated alpha-spectrin (alpha-fodrin) breakdown products (SBDP's) in a maitotoxin-dose-dependent manner. Two calpain inhibitors (MDl28170 and SJA6017) reduced p35 processing but were unchanged when exposed to the caspase inhibitor carbobenzoxy-Asp-CH(2)OC(=O)-2, 6-dichlorobenzene or the proteasome inhibitors (lactacystin and Z-Ile-Glu(OtBu)Ala-Leu-CHO). p35 protein was also degraded to p25 when rat brain lysate was subjected to in vitro digestion with purified mu- and m-calpains. Additionally, in a rat temporary middle cerebral artery occlusion model, p35 processing to p25 again paralleled SBDP formation in the ischemic core. Lastly, in malonate-injured rat brains, the ipsilateral side showed a striking correlation of SBDP formation with p35 to p25 conversion and tau phosphorylation (at Ser202 and Thr205) increase. These data suggest that calpain is a major neuronal protease capable of converting p35 to p25 and might play a pathological role of activating cdk5 and its phosphorylation of tau in Alzheimer's disease.

Animals↗
PubMed2000

Dosimetric effects of edema in permanent prostate seed implants: a rigorous solution.

PURPOSE: To derive a rigorous analytic solution to the dosimetric effects of prostate edema so that its impact on the conventional pre-implant and post-implant dosimetry can be studied for any given radioactive isotope and edema characteristics. METHODS AND MATERIALS: The edema characteristics observed by Waterman et al (Int. J. Rad. Onc. Biol. Phys, 41:1069-1077; 1998) was used to model the time evolution of the prostate and the seed locations. The total dose to any part of prostate tissue from a seed implant was calculated analytically by parameterizing the dose fall-off from a radioactive seed as a single inverse power function of distance, with proper account of the edema-induced time evolution. The dosimetric impact of prostate edema was determined by comparing the dose calculated with full consideration of prostate edema to that calculated with the conventional dosimetry approach where the seed locations and the target volume are assumed to be stationary. RESULTS: A rigorous analytic solution on the relative dosimetric effects of prostate edema was obtained. This solution proved explicitly that the relative dosimetric effects of edema, as found in the previous numerical studies by Yue et. al. (Int. J. Radiat. Oncol. Biol. Phys. 43, 447-454, 1999), are independent of the size and the shape of the implant target volume and are independent of the number and the locations of the seeds implanted. It also showed that the magnitude of relative dosimetric effects is independent of the location of dose evaluation point within the edematous target volume. It implies that the relative dosimetric effects of prostate edema are universal with respect to a given isotope and edema characteristic. A set of master tables for the relative dosimetric effects of edema were obtained for a wide range of edema characteristics for both (125)I and (103)Pd prostate seed implants. CONCLUSIONS: A rigorous analytic solution of the relative dosimetric effects of prostate edema has been derived for a class of edema characterized by Waterman et al. The solution proved that the dosimetric effects caused by the edema are universal functions of edema characteristics for a given isotope. It provides an efficient tool to examine the relative dosimetric effects of edema for any given edema characteristics and for any isotopes that may be considered for prostate implants.

Brachytherapy↗
PubMed2000

American brachytherapy society recommendations for clinical implementation of NIST-1999 standards for (103)palladium brachytherapy. The clinical research committee of the American Brachytherapy Society.

PURPOSE: Recent important developments in palladium-103 ((103)Pd) dosimetry mandate a reevaluation of (103)Pd brachytherapy prescribing practices. METHODS AND MATERIALS: The clinical research committee of the American Brachytherapy Society (ABS) convened a consensus session of brachytherapists and physicists to develop recommendations regarding future dose prescribing guidelines for National Institute of Standards and Technology (NIST-1999) calibrated (103)Pd sources. RESULTS: The ABS recommends that clinicians attempt to reproduce the implant doses delivered and reported in the literature through the past decade. CONCLUSIONS: The following should be immediately implemented for (103)Pd dosimetry: 1) All practicing physicians, physicists, dosimetrists, and suppliers implement NIST-1999 air-kerma strength standard for (103)Pd brachytherapy. 2) All treatment planning systems and dose calculation algorithms must be updated to reflect new dose rate constants. The AAPM-recommended validated value for Theraseed model 200 is 0.665 cGy h(-1) U(-1). The dose rate constant for the Mentor MED3633 seed is currently reported as 0.68 cGy h(-1) U(-1). This latter value and the values for seeds from other manufacturers are awaiting independent confirmation. 3) Physicians who previously prescribed 115 Gy for (103)Pd monotherapy prostate implants should now prescribe 125 Gy. When using (103)Pd as a boost following 45 Gy of external beam irradiation, 100 Gy should be prescribed instead of the previous 90 Gy. It is critical that all three changes be implemented concurrently, because they are interdependent.

Brachytherapy↗
PubMed2000

Histopathological and biochemical changes in the sutural region in craniosynostosis.

OBJECT: Histopathological observations and biochemical analysis of sutural bones in nine patients with craniosynostosis were compared with control subjects of the same age range. METHODS: Microscopic examination in craniosynostosis showed formation of an active osseous front, with higher osteoblastic activity than in controls. Biochemical analysis revealed higher calcium, phosphorus, alkaline phosphatase, phospholipids and chondroitin sulphate-A contents in sutural bones of the same patients. CONCLUSIONS: The present study systematically establishes a premature increase in osteogenesis in the sutures of craniosynostosis patients.

Alkaline Phosphatase↗
PubMed2000

Development and characterization of antibodies specific to caspase-3-produced alpha II-spectrin 120 kDa breakdown product: marker for neuronal apoptosis.

Alpha II-spectrin (alpha-fodrin) is a demonstrated endogenous substrate for caspase-3 in neurons undergoing unscheduled apoptotic death. We have previously identified the caspase cleavage site that yields the distinctive 120 kDa spectrin breakdown product (SBDP120) as (DSLD(1478)*SVEAL). Here, by using a synthetic peptide (NH(2)-SVEALC) mimicking the neo-N-terminal of SBDP120 as antigen, we report the development of chicken antibodies that specifically recognize the SBDP120 generated by in vitro caspase-3 digestion of bovine alpha-spectrin on Western blot. These anti-SBDP120 antibodies recognize SBDP120 generated by two apoptotic challenges (staurosporine, EGTA) to human neuroblastoma SH-SY5Y cells. Yet they neither react with intact alpha-spectrin nor its other fragments on Western blots. These anti-SBDP120 work equally well in detecting SBDP120 generated in rat cerebellar granule neurons undergoing potassium withdrawal-induced apoptosis. In immunocytochemical studies, these antibodies also specifically stained apoptotic SH-SY5Y or CGN's undergoing apoptosis in a caspase- inhibitor-sensitive manner. These anti-SBDP120s might become powerful markers for apoptotic neurons in various neurological or neurodegenerative conditions in vivo.

Animals↗
PubMed2000

Activation of apoptosis-linked caspase(s) in NMDA-injured brains in neonatal rats.

Unilateral injection of 50 nmol of N-methyl-D-aspartate (NMDA) into the left posterior striatum of 7 day-old rat pups induces massive neuronal loss in the ipsilateral hemisphere in 5 days. In this model of excitotoxicity, the form of neuronal death (necrosis vs apoptosis) has not been clearly addressed. Here we report evidence of DNA laddering in the ipsilateral hemisphere 24 h after the NMDA injection. Activation of apoptosis-linked caspase(s) was also identified, as evidenced by (i) the formation of caspase-produced 120 kDa alpha-spectrin breakdown product (SBDP120) and (ii) increase in hydrolysis of caspase-3 substrate acetyl-DEVD-7-amido-4-methylcoumarin in the homogenate from the ipsilateral hemisphere. Lastly, we note that i.p. injection (100 mg/kg) of a pan caspase inhibitor Z-D-DCB attenuates the levels of SBDP120. Our results suggest the presence of caspase-activation in this rat pup model of NMDA toxicity.

Animals↗
PubMed2000

Use of the anti-idiotype antibody vaccine TriAb after autologous stem cell transplantation in patients with metastatic breast cancer.

Between April 1997 and March 1998 we evaluated the immune response and outcome in 11 chemosensitive patients who were treated with the anti-idiotype antibody vaccine TriAb after recovery from intensive therapy and autologous stem cell transplant (ASCT). Triab was commenced after recovery from the acute effects of ASCT; a minimum interval of 1 month was required from completion of consolidation radiotherapy, if given. Nine patients (82%) manifest anti-anti-idiotype antibody (Ab3) responses post ASCT. The maximal Ab3 response was seen after a median of 10 doses (range 5-20), which corresponded to a median of 14 months (range 5-19) post ASCT. Evidence of a T cell proliferative response was seen in eight patients; the response was modest in most of these. At a median follow-up of 24 months (range 22-33) after ASCT, four patients are alive without evidence of disease progression. All four of these patients were in the subgroup with more vigorous immune responses. Subsequent efforts have been directed toward the achievement of higher levels of immune responses more rapidly post ASCT. Bone Marrow Transplantation (2000) 26, 729-735.

Adult↗
PubMed2000

A novel balloon angioplasty catheter impregnated with beta-particle emitting radioisotopes for vascular brachytherapy to prevent restenosis; first in vivo results.

BACKGROUND: According to early clinical trials, vascular brachytherapy performed prior to or shortly after angioplasty is very effective in reducing restenosis rates. The purpose of this study was to investigate the effects of a novel radioactive catheter that allows simultaneous balloon angioplasty and beta-particle irradiation in the prevention of restenosis. MATERIAL AND METHODS: The balloon surface of an angioplasty catheter was impregnated with the radioisotope(32)P. Dosimetry calculations using a Monte Carlo method were performed at a radial distance of 0.2 mm from the balloon surface. Rabbit iliac arteries were dilated and simultaneously irradiated with a dose of 20 Gy delivered to the adventitia. Control arteries were only dilated and not irradiated. Neointimal areas, cell numbers and the perimeter of the arteries were measured by histomorphometry after 6 weeks. RESULTS: Neointima formation was reduced after balloon dilatation and simultaneous beta-particle irradiation using the(32)P impregnated angioplasty catheter as compared to balloon dilatation alone with a non-impregnated catheter (0.09+/-0.06 vs 0.27+/-0.09 mm(2)neointimal area and 168+/-45 vs 360+/-133 cells/0.05 mm(2)neointima, P<0.001 vs control, respectively). In addition, balloon dilatation with the(32)P impregnated angioplasty catheter increased the vessel perimeter as compared to balloon dilatation with a non-impregnated catheter (4. 7+/-0.2 vs 3.9+/-0.3 mm, P<0.001 vs control). CONCLUSIONS: Simultaneous balloon dilatation and vascular brachytherapy with a novel(32)P impregnated angioplasty catheter markedly reduces restenosis in vivo by preventing neointimal hyperplasia and constrictive vascular remodelling.

Angioplasty, Balloon↗
PubMed2000

Congenital bowing of the long bones associated with camptodactyly, talipes equinovarus and agenesis of the corpus callosum.

We report a baby with congenital bowing of the long bones, camptodactyly, talipes equinovarus and radiological features resembling both Stüve-Wiedemann syndrome and Schwartz-Jampel syndrome type 2. The baby had, in addition, agenesis of the corpus callosum. This feature has not been reported in either of these syndromes. It is possible that this baby has a previously undescribed syndrome.

Abnormalities, Multiple↗
PubMed2000

Dose distribution along the transverse axis of a new 125I source for interstitial brachytherapy.

A new encapsulated source of 125I has been introduced for interstitial brachytherapy. This source, isoSTAR model 12501 (manufactured by Imagyn Corp.), consists of a welded titanium tube containing 125I as silver iodide uniformly coated on five silver beads. The dose rate constant and the radial dose function for this source were measured using lithium fluoride thermoluminescent dosimeters in a Solid Water phantom. The value of the dose rate constant is 0.95 cGy h(-1)U(-1) where the unit of air kerma strength is 1 U = 1 cGy h(-1)cm2. The air kerma strength was traceable to the year 2000 primary air kerma strength standard for the model 12501 source at the National Institute of Technology and Standards. The radial dose function for the source was very similar to that for the model 6711 source (manufactured by Nycomed Amersham) for radial distances up to 6 cm. However, the radial dose function is lower in value than that for the model 6702 source (manufactured by Nycomed Amersham) and the model MED3631-A/M Iogold source (manufactured by North American Scientific).

Air↗