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Biomedical subjects

A Narayana

Publications and source records attributed to A Narayana.

At least 19 recordsLinked to original sources

Use of MR spectroscopy and functional imaging in the treatment planning of gliomas.

Routine anatomical imaging with CT and MRI does not reliably indicate the true extent or the most malignant areas of gliomas and cannot identify the functionally critical parts of the brain. The aim of the study was to see if the use of MR spectroscopic imaging (MRSI) along with functional MRI (fMRI) can better define both the target and the critical structures to be avoided to improve radiation delivery in gliomas. 12 patients with gliomas underwent multivoxel MRS and functional imaging using GE processing software. The choline to creatine ratio (Cho:Cr), which represents the degree of abnormality for each individual voxel on MRSI, was derived, converted into a grayscale grading system, fused to the MRI images and then transferred to the planning CT images. An intensity-modulated radiation therapy (IMRT) plan was developed using the dose constraints based on both the anatomical and the functionally critical regions. Cho:Cr consistently identified the gross tumour volume (GTV) within the microscopic disease (clinical target volume, CTV) and allowed dose painting using IMRT. No correlation between MRSI based Cho:Cr > or =2 and MR defined CTV nor their location was noted. However, MRSI defined Cho:Cr > or =3 was smaller by 40% compared with post-contrast T1 weighted MRI defined GTV volumes. fMRI helped in optimizing the orientation of the beams. In conclusion, both MRSI and fMRI provide additional information to conventional imaging that may guide dose painting in treatment planning of gliomas. A Phase I IMRT dose intensification trial in gliomas using this information is planned.

Brain↗

Clinical oncology clerkship for third-year medical students.

BACKGROUND: A two-week elective clerkship in clinical oncology is offered to third-year medical students. METHODS: Two students at a time participated in the rotation and spent time with attendings in a one-to-one setting in outpatient clinics in the cancer specialties. The students also attended multidisciplinary tumor boards. Grand rounds, peer review conferences, and problem-case conferences were attended by the students as well. The students met with an attending for one-hour, twice-per-week to discuss pertinent oncologic cases and problems. The exposure to clinical oncology for two weeks is intended to educate the students relative to the presentation, evaluation, treatment, prognosis, and follow-up for a variety of cancers. RESULTS: The rotation has been highly successful as measured by its popularity and by consistently high course evaluations from the medical students. CONCLUSION: The overall quality of the learning experience for the rotation has been rated by the students as the highest among all courses in their four-year curriculum.

Clinical Clerkship↗

Stomal recurrence in patients with T1 glottic cancer after salvage laryngectomy for radiotherapy failures: role of p53 overexpression and subglottic extension.

The role of p53 overexpression in the development of stomal recurrence was studied in patients with T1 glottic cancer who had undergone salvage laryngectomy after primary radiotherapy failure (first recurrence). The role of subglottic extension of the recurrent tumor in the development of stomal recurrence was also studied. One hundred fourteen patients with T1 squamous cell carcinoma of the glottic larynx were irradiated with curative intent. A local recurrence (first recurrence) developed in 23 patients (20%), and salvage laryngectomy was performed for 20 of these patients. No postlaryngectomy radiation therapy was included in the treatment of recurrences. Several risk factors thought to be significant in the development of stomal recurrence were analyzed in these 20 patients. Prognostic factors analyzed include: p53 overexpression in the preradiation biopsy specimen, subglottic extension of the first recurrence, thyroid cartilage and lymph node involvement at the time of first recurrence, emergency tracheostomy performed before salvage laryngectomy, and the laryngectomy procedure performed for first recurrence. Presence of p53 protein in the preradiation biopsy specimen of laryngeal cancer did not show any adverse effect on the development of stomal recurrence. Stomal recurrence developed in 27% of patients with positive biopsies and in 20% of patients with negative biopsies (p = 1.00). Subglottic extension of the first recurrence was associated with an increased incidence of stomal recurrence. Rates of stomal recurrence were 6% in patients without subglottic extension and 100% in patients with subglottic extension (p = 0.001). All other risk factors studied showed no effect on stomal recurrence. In this study, p53 overexpression showed no effect on the development of stomal recurrence after salvage laryngectomy in patients with T1 glottic cancer. Conversely, subglottic extension of the recurrence was found to be strongly associated with stomal recurrence. All other factors analyzed showed no effect on stomal recurrence.

Carcinoma, Squamous Cell↗

Posterior fossa boost in medulloblastoma: an analysis of dose to surrounding structures using 3-dimensional (conformal) radiotherapy.

PURPOSE: The purpose of this study was to compare three different techniques of delivering the posterior fossa boost in patients with medulloblastoma. METHODS AND MATERIALS: Five patients underwent CT simulation for treatment planning of the posterior fossa boost. For each slice, the posterior fossa was contoured in addition to the cochlea, non-posterior fossa brain, pituitary gland, mandible, parotid glands, thyroid gland, pharynx, and cervical spinal cord. For each patient, plans for three techniques of delivering the posterior fossa boost were compared. Technique A utilized parallel-opposed lateral fields using bony landmarks (2-dimensional radiotherapy); the other two techniques were planned using 3-dimensional radiotherapy. Technique B utilized a pair of coplanar wedged posterior oblique beams, whereas Technique C utilized a pair of posterior oblique fields and a vertex field. Dose-volume histograms (DVH) were obtained for each of the organs contoured and for each technique and patient. The maximum, minimum, and mean dose to each organ were determined using the DVH program in our treatment planning system. RESULTS: In 3 of 5 patients, the planning target volume (PTV) was not included in the treatment field with Technique A. The cochlea received 100%, 50%, and 42% of the prescribed posterior fossa dose using Techniques A, B, and C respectively. The mean dose to the non-posterior fossa brain was highest with Technique C, intermediate with Technique A, and lowest for Technique B. The mean dose to the non-posterior fossa brain with Technique B was comparable to the mean non-posterior fossa brain dose delivered using parallel-opposed lateral fields based on the CT definition of the PTV. Likewise, mean dose to the pituitary gland was lowest for Technique B. Both Techniques B and C were associated with a higher mean dose to the thyroid gland, mandible, parotid glands, and pharynx. CONCLUSIONS: The use of Technique B minimized the radiotherapy dose to the cochlea, pituitary gland, and non-posterior fossa brain. Contrary to what one may expect, conformal radiotherapy using Technique B did not deliver a higher dose to the non-posterior fossa brain over standard parallel-opposed lateral fields. Other advantages of conformal techniques B and C over 2-dimensional radiotherapy are the inclusion of the PTV in all patients and a lower mean dose to the pituitary gland. The main disadvantage of conformal Techniques B and C employed in our patients is a higher mean dose to the thyroid gland and other tissues in the neck.

Brain↗

P53 overexpression is associated with bulky tumor and poor local control in T1 glottic cancer.

PURPOSE: To study the role of two possible prognostic factors, p53 and tumor bulk, and their interaction with other tumor and treatment variables in early-stage laryngeal cancer patients treated with curative radiotherapy. METHODS: One hundred two patients with T1N0M0 squamous cell carcinoma of the glottic larynx treated with definitive radiotherapy were analyzed. p53 status in pretreatment biopsy specimens was assessed by immunohistochemistry (IHC) using mouse monoclonal antibody DO-7. Tumors were classified as small surface lesions or bulky tumors. All tumor-related and treatment-related variables which might influence the outcome were analyzed. Local control after definitive radiotherapy was the end point of the study. RESULTS: The local control at 5 years for the entire group of patients was 78% (80/102) and 91% (93/102) after surgical salvage. p53 overexpression by IHC was seen in 37% (38/102) of patients. Tumors were classified as small volume in 69 (68%) and bulky in 33 (32%) patients. Five-year local control was 48% for p53-positive patients as compared to 94% for p53-negative patients (p = 0.0001). Tumor bulk was the other important prognostic factor, with 5-year local control of 91% for small tumors and 48% for bulky tumors (p = 0.0001). Patients who had both p53 positivity and bulky tumors did worse, with a 5-year local control of 23% as compared to 92% for all other groups combined (p = 0.0001). Among other variables, only the length of radiation time was of borderline significance. CONCLUSION: Both p53 overexpression and tumor bulk are independent prognostic factors for local control in early-stage glottic cancer treated with curative radiotherapy. The precise relationship between a genetic event, the p53 mutation, and an observable phenotype expression such as tumor bulk needs to be further defined.

Aged↗

The cranial-spinal junction in medulloblastoma: does it matter?

PURPOSE: Late effects of treatment in children and young adults with medulloblastoma can be influenced by the technique employed in radiating the craniospinal axis. The purpose of this study is to determine whether the placement of the cranial-spinal junction has an impact on dose to the cervical spinal cord and surrounding organs. METHODS AND MATERIALS: Five patients underwent computed tomography (CT) simulation in the prone position for craniospinal irradiation. A dose of 36 Gy was prescribed to the entire neuraxis. The doses to the cervical spinal cord and surrounding organs were calculated using a cranial-spinal junction at the C1-C2 vertebral interspace (high junction) or at the lowest point in the neck, with exclusion of the shoulders in the lateral cranial fields (low junction). The volume of critical organs at risk, as well as dose to these structures using the cranial and spinal field(s) were outlined and calculated using the CMS FOCUS 3-dimensional treatment planning system. RESULTS: The average dose to the cervical spinal cord was 11.9% higher than the prescribed dose with the low junction, and 6.7% higher with the high junction. However, doses to the thyroid gland, mandible, pharynx, and larynx were increased by an average of 29.6%, 75.8%, 70.6%, and 227.7%, respectively, by the use of the high junction compared to the low junction. CONCLUSION: A higher dose to the cervical spinal cord can be minimized by using a high junction. However, this would be at the cost of substantially increased doses to surrounding organs such as the thyroid gland, mandible, pharynx, and larynx. This can be critical in children and young adults, where hypothyroidism, mandibular hypoplasia, and development of second malignancies may be a late sequela of radiation therapy.

Adolescent↗

Second primary tumors in laryngeal cancer: results of long-term follow-up.

PURPOSE: The development of second primary tumors (SPTs) is the most important factor determining the survival in early-stage head and neck cancer patients, whose first tumor has been successfully treated. New methods of examining genetic changes have raised doubts about the validity of the widely held field cancerization hypothesis as the cause of SPTs, and an alternative hypothesis of monoclonal origin has been proposed. The objectives of this study were to look at the pattern of development of SPTs and the possible factors influencing the incidence of SPTs and the survival in early-stage laryngeal cancer with long-term follow-up. METHODS AND MATERIALS: One hundred forty-four consecutive patients of T1N0M0 squamous cell carcinoma of the true vocal cord treated with definitive radiotherapy between 1976 and 1992 were analyzed. The incidence, time to development, and survival of aerodigestive and other SPTs were noted. p53 overexpression indicating a mutated p53 gene was analyzed by immunohistochemistry. RESULTS: With a median follow-up of 6 years (range 2-20 years), 42 patients developed a SPT, 24 in upper aerodigestive tract and lung and 18 at other sites. The actuarial incidence of developing a SPT at 5, 10, and 15 years was 23%, 44%, and 48.7% respectively. The median time interval for development of SPT in an upper aerodigestive tract was 21 months as opposed to 50 months for other sites (p = 0.02). The most common sites of SPTs included lung for upper aerodigestive tract; and prostate, followed by colon, for other sites. The actuarial risk of developing a nonaerodigestive SPT at 5 and 10 years was 35% and 55% respectively. p53 status affected neither the incidence of SPT nor the survival. SPTs were the leading cause of death in these early-stage laryngeal cancer patients. CONCLUSION: The origin of SPTs seems to be multifactorial, involving both the field cancerization effect and an increased baseline genetic predisposition. Until more reliable genetic markers are developed, chemoprevention remains the best treatment option at preventing SPTs in these early-stage patients.

Adult↗

Is p53 an independent prognostic factor in patients with laryngeal carcinoma?

BACKGROUND: Carcinoma of the true vocal cord represents the earliest clinically recognizable invasive malignancy in the head and neck region and provides a unique model for studying possible prognostic genetic markers. The aim of this study was to determine whether p53 overexpression correlated with tumor recurrence in a homogenous population of patients with early stage glottic carcinoma treated with radiotherapy alone. METHODS: One hundred and fourteen patients with T1N0M0 squamous cell carcinoma of the glottis were treated with curative radiotherapy between 1976 and 1990. With a median follow-up of 6 years, actuarial local control was 80% with 23 local recurrences. Laryngeal biopsy specimens obtained prior to radiation therapy were analyzed retrospectively in 22 patients. Forty-five patients with local control were used as a control group. p53 overexpression indicating a mutated p53 gene was analyzed by immunohistochemistry using the mouse monoclonal antibody D0-7. RESULTS: Approximately 82% of carcinomas that recurred locally expressed p53 compared with only 29% of those with local control (P < 0.001). No significant relation was noted between p53 expression and histologic grade. Intensity of staining did not predict tumor recurrence. CONCLUSIONS: The authors believe that this case-controlled study demonstrated the role of p53 as an independent prognostic factor in patients with early stage glottic carcinoma.

Actuarial Analysis↗

Synchronous block in DNA synthesis initiation with change in chromatin topology mediated by VP16.

The impact of chromatin topology on the DNA synthetic process was studied in the human squamous-cell carcinoma cell line SQ-20B. A 1-h exposure < or = 10 microM VP16 produced an increase in DNA supercoil tension, measured by recording laser light scatter from salt-extracted nuclei. This change was precisely paralleled by a decrease in DNA synthesis. The effects on both DNA supercoiling and DNA synthesis were suppressed at VP16 concentrations between 10 and 20 microM. The changes in DNA supercoiling and synthesis at VP16 concentrations -10 microM were eliminated by coincubation with mimosine, a DNA synthesis initiator poison. We conclude that brief exposure to low concentrations of VP16 disturbs the balance of torsional energy within discrete replicon domains by affecting normal topoisomerase II activity at sites of replication initiation. The resultant increase in negative supercoil tension mediates a topologic checkpoint, limiting the initiation of DNA synthesis. Such a checkpoint may be a common pathway for control, both during the normal replicative cycle and subsequent to DNA damage.

Cell Nucleus↗

Medical manuscripts in Sri Venkateshwara University Oriental Research Institute, Tirupathi, A. P.

Sri Venkateshwara Oriental Research Institute, Tirupati, was founded in 1939, with an object of collecting old, rare and important manuscripts from all parts of the state to conserve and publish the same for the benefit of coming generations. The total number of the manuscripts preserved in the Institute is 10,672, classified under 45 different heads out of which 137 manuscripts are related to medicine.

Academies and Institutes↗

Topologically constrained domains of supercoiled DNA in eukaryotic cells.

The size of supercoiled, topologically constrained DNA domains within the squamous carcinoma cell line SQ-20B were determined by direct comparison with a panel of irradiated supercoiled plasmid DNAs. Loss of supercoiling in plasmids was determined by gel electrophoresis and in cells by nucleoid flow cytometry. Comparison of dose-response data for plasmid relaxation with that obtained from SQ-20B cells enabled a direct estimation of supercoil target size in these cells. Plasmids pUCD9P (3.9 kbp), pXT-1 (10.1 kbp), pdBPV-MMT-neo (14.6 kbp), pRK290 (20.0 kbp), and R6K (38 kbp) were used and analyzed under the same exposure conditions as nucleoid DNA. Two sizes of topologically closed domains were found in nucleoids of 0.51+/-0.17Mbp and 1.34+/-0.3 Mbp. In an attempt to relate these large-scale organizations of DNA with function, cells were exposed to the DNA topoisomerase II inhibitor, VP16 and the G1/S cell cycle blocking agent mimosine. A 1 h exposure to VP16 was effective in reducing DNA synthesis which was associated with a parallel increase in nucleoid supercoiling. Addition of the G1 > S inhibitor mimosine enhanced both responses. It is concluded that chromosomes and interphase nuclei are organized into at least two sizes of topologically constrained domains of DNA which may have functional relevance to the control and execution of DNA synthesis.

Carcinoma, Squamous Cell↗

Todaramalla.

Todaramalla was a famous physician, scholar, statesman, Finance and Revenue Minister in the court of Akbar. One of the oldest commentary namely 'Manojna' was written by him on Ashtanga Hridaya. He was patriot of Ayurveda and author of 23 series of works in the form of an encyclopedia called 'Todarananda'. Ayurveda saukhyam is one among the Todarananda. The biography of Todaramalla has been presented here.

History, 16th Century↗

Historical perspectives of the twak rogas (Kushtha).

In the doctrines of Ayurveda the twak rogas are known by the general term Kushtha. Atharvaveda describes the twak roga in the name of Kilasa, palita, with the clinical picture of grey and white spots, generally from deeper layers of skin and referred the herbal remedies. Almost all the samhitas uniformly classified Kushtha as Maha Kushtha and Kshudra Kushtha, but there is difference of opinion about the number in each group. The historical perspectives of the Twak rogas (Kushtha) are being presented according to Rigveda, Atharvaveda, Charaka, Sushruta, Vagbhata, Madhavakara Todaramalla.

Disease↗

A brief descriptive catalogue of Ayurvedic palm leaves manuscripts procured and preserved in the Indian Institute of Medicine.

It seems the survey for medical manuscripts has not been done thoroughly so far in India particularly in Andhra Pradesh. Though few Researchers toured many important places and collected a number of manuscripts, but still there are many villages and several families of physicians and scholars possessing many manuscripts, are not covered. One of the aims and objects of the Indian Institute of History of Medicine is to procure and study the rare and uncared medical manuscripts. There are many difficulties in this task as many of the families in possession of the manuscripts are generally not prepared to hand over the ancestry property i.e., manuscripts to any individual or institution due to their sentiments, though they are not able to preserve or make use of same properly. However, efforts were made by the Institute in this direction, visiting several families of hereditary physicians residing in different part of Andhra Pradesh, and procured 12 such valuable palm leaves manuscripts pertaining to Ayurveda and preserved in the Institute. A brief descriptive catalogue of these manuscripts is presented here.

Academies and Institutes↗

A medico-historical review of Arjuna

Ancient Indian Medical knowledge known as Ayurveda goes back to a immemorial past. The Vedas and Puranas refer various materials of medical importance including herbs, plants and trees etc. The ancient medical scientists have mentioned the properties of the Arjuna, and recommended mainly for the management of Hirta/Rudhira vikaras, Vrana, Prameha, Visa Vikaras, Asrugdhara, Kshetriya/Shukra dosha etc. The modern medical/Botanical scientists have also carried out so many researches on Arjuna and do not find any difference with the ancestery knowledge.

History, Ancient↗

Khadira (Acasia Catechu Linn.) - A medico-historical review.

Indigenous Medical wisdom in India known as Ayurveda goes back to a hoary past. We find references in Vedas not only to medical science but to various drugs also. The medico-historical review of Khadira (Acasia Catechu linn.) including the historical perspectives, identity, varieties, formulae and therapeutic usage etc. is presented here, based on the classical treatises, medical lexicons, commentaries and other compilations, covering the from Vedic period to present times.

History, Ancient↗