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Biomedical subjects

S Nag

Publications and source records attributed to S Nag.

At least 19 recordsLinked to original sources
PubMed2001

Intraoperative high-dose-rate brachytherapy for the treatment of pediatric tumors: the Ohio State University experience.

PURPOSE: To determine whether intraoperative high-dose-rate brachytherapy (IO-HDRBT) can be used to decrease the dose of external beam radiotherapy (EBRT) in the treatment of children with soft-tissue sarcomas and, thereby, reduce morbidity without compromising local control. METHODS AND MATERIALS: From March 1992 through April 1999, 13 pediatric patients were treated with IO-HDRBT, low-dose EBRT, chemotherapy, and radical surgery at 21 sites that were not amenable to intraoperative electron beam therapy. The IO-HDRBT dose at 5 mm depth was 10 to 12.5 Gy for close margins/microscopic disease at 14 sites and 12.5 to 15 Gy for gross disease at 7 sites. The treatment volumes ranged from 4 to 96 cm(3) (mean 27). The EBRT dose was limited to 27-30 Gy in most cases to minimize growth retardation and preserve normal organ function. RESULTS: After a median follow-up of 47 months (range 12-97), 11 patients were alive and without evidence of disease (overall survival rate 85%, 4-year actuarial survival rate 77%). Of the 2 who died, 1 had Stage III pulmonary blastoma with a sacral recurrence; the other had Stage IV undifferentiated synovial sarcoma with a pulmonary recurrence. One local failure occurred in a patient with gross residual disease after incomplete resection for Stage IV pulmonary blastoma. The local control rate was 95%, and morbidity was observed in 3 patients (23%). One patient developed impaired orbital growth with mild ptosis. Another patient required orthopedic pinning of her femoral subcapital epiphysis and construction of a neobladder secondary to urethral obstruction. The third patient required reimplantation of her autotransplanted kidney secondary to chronic urinary tract infection and ureteral reflux. CONCLUSIONS: IO-HDRBT allowed for reduction in EBRT without compromising local control or disease-free survival in children with soft-tissue sarcomas. Tumor beds inaccessible to electron beam methods could be satisfactorily encompassed with IO-HDRBT techniques.

Adolescent↗
PubMed2001

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for head-and-neck carcinoma.

PURPOSE: To develop recommendations for use of high-dose-rate (HDR) brachytherapy in patients with head-and-neck cancer. METHODS: A panel consisting of members of the American Brachytherapy Society (ABS) performed a literature review, added information based upon their clinical experience, and formulated recommendations for head-and-neck HDR brachytherapy. RESULTS: The ABS recommends the use of brachytherapy as a component of the treatment of head-and-neck tumors. However, the ABS recognizes that some radiation oncologists are reluctant to employ brachytherapy in the head-and-neck region because of the complexity of the postoperative management and concerns about radiation safety. In this regard, HDR eliminates unwanted radiation exposure and thereby permits unrestricted delivery of clinical care to these brachytherapy patients. The ABS made specific recommendations for previously untreated and recurrent head-and-neck cancer patients on patient selection criteria, implant techniques, target volume definition, and HDR treatment parameters (such as time, dose, and fractionation schedules). Suggestions were provided for treatment with HDR alone and in combination with external beam radiation therapy. It should be recognized that only limited experiences exist with HDR brachytherapy in patients with head-and-neck cancers. Therefore, some of these suggested doses have not been extensively tested in clinical practice. Hence, these guidelines will be updated as significant new outcome data are available. Any clinician following these guidelines is expected to use clinical judgment to determine an individual patient's treatment. CONCLUSIONS: Little has been published in the clinical literature on HDR brachytherapy in head-and-neck cancer. Based upon the available information and the clinical experience of the panel members, general and site-specific recommendations were offered. Areas for further investigations were identified.

Brachytherapy↗
PubMed2001

The American Brachytherapy Society recommendations for brachytherapy of soft tissue sarcomas.

PURPOSE: This report presents the American Brachytherapy Society (ABS) guidelines for the use of brachytherapy for patients with soft tissue sarcoma. METHODS AND MATERIALS: Members of the ABS with expertise in soft tissue sarcoma formulated brachytherapy guidelines based upon their clinical experience and a review of the literature. The Board of Directors of the ABS approved the final report. RESULTS: Brachytherapy used alone or in combination with external beam irradiation is an established means of safely providing adjuvant local treatment after resection for soft tissue sarcomas in adults and in children. Brachytherapy options include low dose rate techniques with iridium 192 or iodine 125, fractionated high dose rate brachytherapy, or intraoperative high dose rate therapy. Recommendations are made for patient selection, techniques, dose rates, and dosages. Complications and possible interventions to minimize their occurrence and severity are reviewed. CONCLUSION: Brachytherapy represents an effective means of enhancing the therapeutic ratio, offering both biologic and dosimetric advantage in the treatment of patients with soft tissue sarcoma. The treatment approach used depends upon the institution, physician expertise, and the clinical situation. Guidelines are established for the use of brachytherapy in the treatment of soft tissue sarcomas in adults and in children. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as further clinical results become available.

Adult↗
PubMed2001

The effect of age on the response of the rat brains to continuous beta-amyloid infusion.

Young (3 months old) and aging (18-21 months old) rats were infused intracerebroventricularly with beta-amyloid (1-40; 4.2 nmol) for 14 days. In both age groups, beta-amyloid led to deficits in water-maze and decreased choline acetyltransferase activity and somatostatin levels. Cortical substance P levels also decreased whereas neuropeptide Y levels remained unaltered. There were no significant age dependent differences among these neurochemicals except a decrease in hippocampal neuropeptide Y levels in the aging group. It is concluded that young and aging rat brains respond similarly to beta-amyloid infusion.

Aging↗
PubMed2001

Chronic intracerebroventricular exposure to beta-amyloid(1-40) impairs object recognition but does not affect spontaneous locomotor activity or sensorimotor gating in the rat.

This study examined the cognitive effects of chronic in vivo exposure to beta-amyloid(1-40) via the intracerebroventricular route on two distinct paradigms. The first test evaluated a form of early attentional control referred to as sensorimotor gating in which an antecedent weak prepulse stimulus modulates the reactivity to a subsequent startle-eliciting stimulus. The second test utilized the spontaneous preference for a novel object over that of a familiar one in rats as a measure of object recognition memory. We found that beta-amyloid exposure leads to a severe deficit in the object memory test but spares sensorimotor gating. Moreover, unlike the water maze deficit induced by beta-amyloid (Nag et al., in preparation), the deficit on object recognition was resistant to amelioration by systemic physostigmine treatment at a dose of 0.06 mg/kg per day intraperitoneally. The present results add to previous reports that beta-amyloid exposure can lead to deficits on hippocampal lesion sensitive tasks, suggesting that dysfunction of the rhinal cortices in addition to that of the septohippocampal system is implicated in beta-amyloid-induced behavioral impairments. It therefore lends support to the hypothesis that beta-amyloid exposure can lead to severe impairment across multiple memory systems.

Acoustic Stimulation↗
PubMed2001

Brachytherapy in the treatment of breast cancer.

Whole-breast external-beam radiation therapy (EBRT) involves a 6-week course of fractionated treatments. In contrast, brachytherapy can be completed in a 4- to 5-day treatment course. Because of this shortened time frame, there has been interest in breast brachytherapy as a sole modality after lumpectomy. The American Brachytherapy Society (ABS) has issued guidelines specifically for the use of brachytherapy in breast carcinoma. In these guidelines, the ABS addresses important areas of controversy related to the indications, execution, and evaluation of breast implants when utilized in the following settings: as the sole treatment modality following lumpectomy, as an alternative to a 6-week course of EBRT following lumpectomy, as a boost following whole-breast irradiation, and for the treatment of local recurrences following breast-conservation treatment. The ABS recommends a precise definition and meticulous delineation of the clinical target volume. In addition, the Society recommends the routine use of dose-volume histograms and a dose-homogeneity index as tools to ensure reproducible brachytherapy and to allow interinstitutional comparisons. Brachytherapy as a sole modality is currently considered investigational and should be performed in the context of a controlled clinical trial. Practitioners and cooperative groups are encouraged to use these guidelines to formulate treatment and dose-reporting policies, but responsibility for medical decisions ultimately rests with the treating radiation oncologist.

Brachytherapy↗
PubMed2001

Expression of nitric oxide synthases and nitrotyrosine during blood-brain barrier breakdown and repair after cold injury.

This study was undertaken to determine whether the blood-brain barrier (BBB) breakdown and cerebral edema occurring post-trauma are associated with overexpression of the endothelial (e) and inducible (i) nitric oxide synthases (NOS), enzymes responsible for nitric oxide (NO) biosynthesis. These enzymes were determined quantitatively at the mRNA level and qualitatively at the protein level in the rat cerebral cortical cold injury model, during a period up to 6 days post-injury. In addition, peroxynitrite generation at the lesion site was detected by immunolocalization of nitrotyrosine as a marker of NO-superoxide interactions. These studies were correlated with the permeability status of the BBB by immunohistochemical detection of endogenous fibronectin extravasation in the same brains. BBB breakdown was immediate in lesion vessels, it was present as early as 10 minutes post-lesion and delayed in perilesional vessels that showed maximal BBB breakdown between 2-4 days. The BBB was restored to normal at 6 days post-lesion. An increase in both eNOS and iNOS mRNA was observed at the lesion site as compared with the contralateral hemisphere at 12 hours, 2 days, and 4 days. The mRNA returned to resting levels by 6 days. Increased eNOS protein was observed in the endothelium of permeable perilesional vessels and neovessels and in the endothelium of the hyperplastic pial vessels overlying the lesion site. iNOS protein was observed initially in polymorphonuclear leukocytes at the lesion site and later in macrophages, endothelial cells, and the smooth muscle cells of the overlying pial vessels. Furthermore, nitrotyrosine was demonstrated at the lesion site up to 5 days. Up-regulation of the NO synthases at both the mRNA and protein level accompanied by presence of nitrotyrosine during BBB breakdown and angiogenesis suggests that NO has a role in the pathogenesis of these processes.

Animals↗
PubMed2001

Audit of influenza and pneumococcal vaccination uptake in diabetic patients attending secondary care in the Northern Region.

AIMS: To document uptake of influenza and pneumococcal vaccination in diabetic patients attending secondary care in the Northern Region, and to explore influencing factors. METHODS: Diabetic patients attending out-patients in Middlesbrough, Gateshead and Newcastle were questioned from October 1999 to March 2000. Physicians inquired about influenza and pneumococcal vaccination status using a standardized questionnaire. Data collected included age, year of diagnosis, duration of diabetes, type of diabetes, and the presence of other recognized indications for vaccination. RESULTS: Two hundred and sixty-eight diabetic patients, 42% (113/268) with Type 1 diabetes, 34% (91/268) with ischaemic heart disease, 10% (26/268) with chronic pulmonary disease (CPD) and 10% (27/268) with chronic renal disease, were questioned. Thirty-five percent (93/268) of patients received both influenza and pneumococcal vaccines, 24% (64/268) received only influenza vaccine, and none received pneumococcus vaccine alone. Most vaccinees received advice about influenza and pneumococcal vaccination from their general practitioner (90% (142/157) and 87% (81/93), respectively). A large number of non-vaccinees were unaware of the need for influenza and pneumococcal vaccination (69% (76/111) and 91% (159/175), respectively). Using multiple logistic regression co-existing CPD increased the odds of receiving influenza (odds ratio (OR) (95% confidence interval (CI)) = 1.99 (1.07-14.12)) or pneumococcal (OR = 3.77 (1.69-21.76)) vaccination. Furthermore, each 1-year increase in age increased the chance of receiving influenza or pneumococcal vaccination by 22% (OR = 1.22 (1.09-1.67) and 29% (OR = 1.29 (1.07-1.72)), respectively. CONCLUSIONS: Vaccination rates in these diabetic patients are unsatisfactory. Secondary care health professionals might increase rates by raising the topic in consultations. Diabet. Med. 18, 599-603 (2001)

Adolescent↗
PubMed2001

Long-term follow-up on an intensified treatment regimen for advanced resectable head and neck squamous cell carcinomas.

From February 1993 through July 1994, 37 patients with stage III-IV squamous cell carcinomas of the oral cavity, oropharynx, or hypopharynx (stage II-IV) were registered to a treatment regimen consisting of preoperative continuous infusion cisplatin (80 mg/m2/80 hours) with hyperfractionated external beam radiotherapy (9.1 Gy/7 fractions of 1.3 Gy BID), surgical resection, intraoperative radiotherapy (7.5 Gy), and postoperative radiotherapy (40 Gy) with concurrent cisplatin (100 mg/m2 x 2 courses). The objectives of the regimen were to improve patient compliance while also increasing treatment intensity. The purpose of this article is to report the local, regional (nodal), and distant disease control of these patients after an extended time at risk (median 40 months). Overall compliance (73%), local control at primary site (97%), and regional nodal control (95%) were excellent. The rate of distant metastasis was 19%. Absolute survival at 48 months was 45.9%.

Carcinoma, Squamous Cell↗
PubMed2001

Differential response of sensory and motor axons in nerve allografts after withdrawal of immunosuppressive therapy.

OBJECT: Rejection of nerve allografts and loss of regenerated host axons after withdrawal of immunosuppressive therapy poses an ongoing challenge in peripheral nerve repair. The present report is of a blinded prospective controlled study in which an established rat model of nerve allotransplantation is used to examine the effect of fiber type on survival and degeneration of nerve allografts after discontinuation of immunosuppression. The authors hypothesized that sensory axons will selectively resist a rejection response, whereas motor axons will degenerate. METHODS: Four-centimeter nerve segments from ACI rats were grafted into peroneal and sural (mixed) or saphenous (sensory) nerve gaps in Lewis rats. In some rats, L4-6 dorsal root ganglia were ablated before grafting, creating pure motor sural and peroneal nerves. All rats received 12 weeks of immunosuppressive therapy to support nerve regeneration into allografts. Immunosuppression with cyclosporin was then withdrawn. At planned death (12-18 weeks postsurgery), graft tissue was subjected to histomorphometric analysis for evaluation of axon survival and loss. Graft rejection led to loss of all axons in approximately 60% of the allograft segments. The mixed nerve group was most prone to complete rejection, with significantly lowered axon counts at Weeks 16 and 18 compared with the Week 12 baseline. Axons from the sensory nerve were least likely to degenerate. The pure motor nerve group axons demonstrated intermediate sensitivity, with a selective loss of larger axons at Week 16 and a significant decrease in axon counts from the Week 12 baseline at Week 18. CONCLUSIONS: Whereas the majority of axons are lost after withdrawal of immunosuppressive therapy from nerve allografts, there is a selective survival of axons from cutaneous sensory nerves and smaller-diameter motor fibers. The biological and molecular mechanisms that make some axons impervious to injury remain to be determined.

Animals↗
PubMed2001

Glioblastoma multiforme occurring in a patient treated with gamma knife surgery. Case report and review of the literature.

Stereotactic radiosurgery is being increasingly advocated as the primary modality for treatment of vestibular schwannomas (VS). This modality has been shown to arrest tumor growth, with few associated short-term morbidities, and with possibly better hearing and facial nerve preservation rates than microsurgery. Radiation-induced oncogenesis has long been recognized, although stereotactic radiosurgery de novo induction of a secondary tumor has never been clearly described. The authors report on a patient with a VS who did not have neurofibromatosis Type 2 and who underwent gamma knife surgery (GKS). This patient required microsurgical removal of the VS within 8 months because of development of a tumor cyst with associated brainstem compression and progressive hydrocephalus. The operation resulted in clinical stabilization and freedom from tumor recurrence. Seven and a half years after undergoing GKS, the patient presented with symptoms of raised intracranial pressure. Magnetic resonance imaging demonstrated a new ring-enhancing lesion in the inferior temporal lobe adjacent to the area of radiosurgery, which on craniotomy was confirmed to be a glioblastoma multiforme (GBM). Despite additional conventional external-beam radiation to the temporal lobe, the GBM has progressed. Whereas this first reported case of a GBM within the scatter field of GKS does not conclusively prove a direct causal link, it does fulfill all of Cahan's criteria for radiation-induced neoplasia, and demands increased vigilance for the potential long-term complications of stereotactic radiosurgery, and reporting of any similar cases.

Brain Neoplasms↗
PubMed2000

Early voiding dysfunction associated with prostate brachytherapy.

Introduction: Transperineal prostate brachytherapy is gaining popularity as a treatment for clinically localized carcinoma of the prostate. Very little prospective data exists addressing the issue of complications associated with this procedure. We present an analysis of the early voiding dysfunction associated with prostate brachytherapy. Materials and Methods: Forty-six consecutive patients who underwent Palladium-103 (Pd-103) seed placement for clinically localized prostate carcinoma were evaluated prospectively for any morbidity associated with the procedure. Twenty-three patients completed an International Prostate Symptom Score (IPSS) questionnaire preoperatively, at their first postoperative visit, and at their second postoperative visit. The total IPSS, each of the seven individual components, and the "bother" score were evaluated separately for each visit, and statistical significance was determined. Results: Urinary retention occurred in 7/46 patients (15%). Of these, 5 were able to void spontaneously after catheter removal. One patient is maintained with a suprapubic tube, and one patient is currently on continuous intermittent catheterization. Baseline IPSS was 7.1 and this went to 20.0 at the first postoperative visit (p<0.001). By the second postoperative visit, the IPSS was 8.0. Conclusions: In our experience, prostate brachytherapy for localized carcinoma of the prostate is associated with a 15% catheterization rate and a significant increase in the IPSS (7.1 to 20.0). This increase in the IPSS seems to be self-limited. Patients need to be educated on these issues prior to prostate brachytherapy.

Journal Article↗
PubMed2000

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the endometrium.

PURPOSE: To develop recommendations for use of high-dose-rate (HDR) brachytherapy in patients with endometrial cancer. METHODS: A panel of members of the American Brachytherapy Society (ABS) performed a literature review, supplemented their clinical experience, and formulated recommendations for endometrial HDR brachytherapy. RESULTS: The ABS endorses the National Comprehensive Cancer Network (NCCN) guidelines for indications for radiation therapy for patients with endometrial cancer and the guidelines on HDR quality assurance of the American Association on Physicists in Medicine (AAPM). The ABS made specific recommendations for HDR applicator selection, insertion techniques, target volume definition, dose fractionation, and specifications for postoperative adjuvant vaginal cuff therapy, for vaginal recurrences, and for medically inoperable primary endometrial cancer patients. The ABS recommends that applicator selection should be based on patient and target volume geometry. The dose prescription point should be clearly specified. The treatment plan should be optimized to conform to the target volume whenever possible while recognizing the limitations of computer optimization. Suggested doses were tabulated for treatment with HDR alone, and in combination with external beam radiation therapy (EBRT), when applicable. For intravaginal brachytherapy, the largest diameter applicator should be selected to ensure close mucosal apposition. Doses should be reported both at the vaginal surface and at 0.5-cm depth irrespective of the dose prescription point. For vaginal recurrences, intracavitary brachytherapy should be restricted to patients with nonbulky (< 0.5-cm thick) disease. Patients with bulky (> 0.5-cm thick) recurrences should be treated with interstitial techniques. For medically inoperable patients, an appropriate applicator that will allow adequate irradiation of the entire uterus should be selected. CONCLUSION: Recommendations are made for HDR brachytherapy for endometrial cancer. Practitioners and cooperative groups are encouraged to use these recommendations to formulate their treatment and dose reporting policies. This will lead to meaningful comparisons of reports from different institutions and lead to advances and appropriate use of HDR.

Brachytherapy↗
PubMed2000

A rapid and sensitive assay method for measuring amine oxidase based on hydrogen peroxide-titanium complex formation.

Hydrogenperoxide (H(2)O(2)) is an end product of diamine and polyamine oxidation by their respective oxidase enzymes. A new sensitive assay method is based on a H(2)O(2)-titanium (Ti) complex formation as an indicator of H(2)O(2) production due to polyamine oxidation. The orange-yellow coloured H(2)O(2)-Ti complex was measured at 410 nm in a Shimadzu spectrophotometer. The assay conditions for maximum diamine oxidase (DAO) and polyamine oxidase (PAO) as standardized here using the hypocotyl tissues of Vigna catjang Endl. cv Pusa Barsati consisted of pH 7.4 (40 mM potassium phosphate buffer), 3 mM substrate (putrescine or spermine), 37 degrees C incubation temperature and 30 min incubation time in the presence of catechol (10(-2) M) used as an inhibitor of both peroxidase and catalase activity. The method described here was significantly more sensitive than the starch-iodide method [T.A. Smith, Biochem. Biophys. Res. Commun. 41 (1970) 1452-1456], which could be improved further if measured under the same assay conditions as described for the H(2)O(2)-Ti method. Sensitivity of the present method was tested by assaying DAO/PAO activity in auxin treated hypocotyls of Vigna and comparing it with the starch-iodide method in two other plant samples.

Journal Article↗
PubMed2000

The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix.

PURPOSE: This report presents guidelines for using high-dose-rate (HDR) brachytherapy in the management of patients with cervical cancer, taking into consideration the current availability of resources in most institutions. METHODS: Members of the American Brachytherapy Society (ABS) with expertise in HDR brachytherapy for cervical cancer performed a literature review, supplemented their clinical experience to formulate guidelines for HDR brachytherapy of cervical cancer. RESULTS: The ABS strongly recommends that definitive irradiation for cervical carcinoma must include brachytherapy as a component. Each institution should follow a consistent treatment policy when performing HDR brachytherapy, including complete documentation of treatment parameters and correlation with clinical outcome, such as pelvic control, survival, and complications. The goals are to treat Point A to at least a total low-dose-rate (LDR) equivalent of 80-85 Gy for early stage disease and 85-90 Gy for advanced stage. The pelvic sidewall dose recommendations are 50-55 Gy for early lesions and 55-65 Gy for advanced ones. The relative doses given by external beam radiation therapy (EBRT) vs. brachytherapy depend upon the initial volume of disease, the ability to displace the bladder and rectum, the degree of tumor regression during pelvic irradiation, and institutional preference. As with LDR brachytherapy, every attempt should be made to keep the bladder and rectal doses below 80 Gy and 75 Gy LDR equivalent doses, respectively. Interstitial brachytherapy should be considered for patients with disease that cannot be optimally encompassed by intracavitary brachytherapy. While recognizing that many efficacious HDR fractionation schedules exist, some suggested dose and fractionation schemes for combining the EBRT with HDR brachytherapy for each stage of disease are presented. These recommendations are intended only as guidelines, and the suggested fractionation schemes have not been thoroughly tested. The responsibility for the medical decisions ultimately rests with the treating radiation oncologist. CONCLUSION: Guidelines are established for HDR brachytherapy for cervical cancer. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies. These guidelines will be modified, as image-based treatment becomes more widely available.

Antineoplastic Agents↗
PubMed2000

DNA-cleavage studies on N-substituted monocyclic enediynes: enhancement of potency by incorporation of intercalating or electron poor aromatic ring and subsequent design of a novel phototriggerable acyclic enediyne.

A number of novel N-substituted enediynes (azaenediynes) 1-4 were synthesized as DNA cleaving agents. Enhancement of DNA cleavage potency was observed with those compounds which could interact with DNA through intercalation of the extended aromatic ring or through electrostatic attraction with electron poor aromatic ring. An acyclic enediyne 5 with a novel phototriggerable device was also synthesized and its DNA-cleaving activity was established.

DNA↗