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Biomedical subjects

N Gupta

Publications and source records attributed to N Gupta.

At least 19 recordsLinked to original sources
PubMed1995

Local control of carcinoma of the tonsil by radiation therapy: an analysis of patterns of fractionation in nine institutions.

PURPOSE: To investigate the importance to outcome of treatment for squamous cell carcinomas of the tonsillar fossa, of dose per fraction, overall treatment duration, and total dose. METHODS AND MATERIALS: A collaborative retrospective study was undertaken in nine centers that used widely different dose-fractionation patterns for external beam radiation therapy. RESULTS: There were 676 eligible cases treated only with photon beams during the years 1976-1985. The probability of local control (of the tonsillar fossa primary) was influenced by both T-stage and N-stage. Significant treatment parameters were total dose and overall treatment duration, but not dose per fraction. Over the range of about 40 to 90% and for a constant overall treatment duration, local tumor control probability increased by nearly 2% for each 1 Gy increase in total dose. For a constant total dose there was a decrease in the probability of local control associated with prolongation of overall treatment duration, presumed to result from accelerated regrowth of surviving tumor clonogens during the course of treatment. If it is assumed that accelerated regrowth occurred at a constant rate and began within 9 days of the start of treatment, an average of 0.53 Gy extra dose per day's extension of treatment would be required to maintain a constant probability of local control. Correspondingly, the probability of local control from a constant dose would be lowered by an average of at least 1% for each day's extension of treatment duration. However, the data are slightly more consistent with an average delay of as long as 30 days before onset of accelerated repopulation, with a consequent increase to an average of 0.73 Gy per day for the value of the compensatory dose. The alpha/beta ratio for this tumor is high enough that the effect of fraction size on the probability of local control can be ignored; a precise estimate is not possible because the best value for beta was close to zero. After accounting for the significant variables studied (treatment time, T-stage, N-stage), the dose-response curves for tumor control were still shallow, suggesting that there are additional causes for heterogeneity of responses among these tumors. CONCLUSIONS: Total dose is important to treatment outcome: After accounting for other treatment variables, there is about a 2% per Gy increase in probability of tumor control over the ranges of control commonly achieved. Overall treatment duration is important. There is at least a 1% per day decrease in tumor control probability if delivery of a constant total dose is prolonged, requiring a compensatory increase in dose by 0.5-0.7 Gy per day to achieve a constant rate of tumor control. Fraction size is not, of itself, an important factor in the response of primary carcinoma of the tonsil. If a tumor has demonstrated a capacity for metastatic spread to lymph nodes, a higher total dose should be considered to achieve control rates at the primary site equivalent to those in node negative patients. Even after accounting for variables such as tumor stage, total dose, and overall treatment duration, there is sufficient heterogeneity in other undocumented determinants of tumor control to cause the tumor control probability curve to be a shallow function of dose.

Analysis of Variance↗
PubMed1995

Late normal tissue sequelae from radiation therapy for carcinoma of the tonsil: patterns of fractionation study of radiobiology.

PURPOSE: To evaluate the influence of dose fractionation and other factors on the development of late complications in mandibular bone, muscle, and mucosa of the oral cavity after external beam radiation therapy for carcinoma of the tonsil. METHODS AND MATERIALS: A retrospective analysis was made of the results in 676 patients treated with a spectrum of fractionation regimens in nine centers during the years 1976-1985. Only severe (Grades 3-4) late complications were analyzed. RESULTS: With more than 5 years follow-up, it was found that total dose was a factor for all three types of complications, but that in other respects, the radiobiology of late-(> 3 months) developing mucosal ulcerations was different from that for mandibular necrosis and muscle injury. Dose per fraction was a significant factor for bone and muscle (estimated alpha/beta values of 0.85 Gy and 3.1 Gy, respectively). By contrast, mucosa showed no influence on response from change in fraction size over the range of approximately 1.0-3.5 Gy. Complications in bone and muscle were not related to overall treatment duration, whereas there was a significant inverse relationship for mucosa breakdown. The rate of development of complications was fastest in mucosa and slowest in bone. The appearance of complications by 4 years after treatment was about 80% of those developing by 8 years in the mucosa, 66% in muscle, and about 50% in bone. The high alpha/beta ratio, inverse relationship with overall treatment duration, and faster development of mucosal complications suggests that they may develop as a consequence of earlier mucosal injury. As anticipated, adequate retrospective analysis of acute complications could not be made even when objective criteria such as weight loss, unplanned delays in completing treatment, or hospitalization during treatment were the measures. Field size was a significant factor for mandible complications, but not for muscle or mucosa. CONCLUSION: The radiobiological characteristics of bone and muscle were those characteristic of other late-responding tissues, whereas late sequelae in mucosa had radiobiological parameters similar to those for acute responses. Field size was a significant factor for bone complications but not for others.

Carcinoma, Squamous Cell↗
PubMed1995

Decision logic for retreatment of asymptomatic lung cancer recurrence based on positron emission tomography findings.

PURPOSE: The purpose of the study was to determine if Positron emission tomography (PET) 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) imaging could detect subclinical local lung cancer recurrence and whether retreatment of such recurrence was feasible and beneficial. METHODS AND MATERIALS: Twenty patients with biopsy proven lung cancer were studied with Positron emission tomography for the purpose of detecting subclinical lung cancer recurrence over a period of 4.25 years. All patients were treated with external radiation as part or all of their therapy. Twenty patients had baseline PET and computed tomography (CT) studies for comparison with later studies. Surviving patients had a total of 40 sequential PET scans and 35 CT scans. The follow-up interval ranged from 5 to 40 months posttreatment. The differential uptake ratio (DUR) was determined for regions of interest of increased FDG uptake. RESULTS: The median DUR value of the 20 baseline PET studies was 5.59. The DUR value of greater than 3 was empirically selected as being positive for tumor detection. On baseline studies, PET had a 100% correlation with the CT findings in regard to detection of the site of primary tumor involvement. Four of 20 patients showed areas of discordance in the mediastinal and hilar areas on initial PET and CT studies. Seven of 17 patients showed discordant posttreatment PET-CT findings. Two false positive PET studies were due to radiation pneumonitis and one to macrophage glycolysis in tumor necrosis. For detection of asymptomatic tumor recurrence, analysis of sequential PET and CT studies, biopsy results, and the patient's clinical course suggested that PET had a sensitivity of 100%, specificity of 89.3%, and accuracy of 92.5%. Computerized Tomography was found to have a sensitivity of 67%, specificity of 85%, and accuracy of 82% for detection of such early-stage recurrence. Five patients went on to have retreatment with external irradiation based upon the PET evidence. Four retreated patients had biopsies that corroborated the positive PET findings, and one patient was retreated on the basis of the qualitative appearance of the posttreatment PET study. Two of the five retreated patients remain alive without evidence of tumor to 34 months following initial therapy. CONCLUSION: Positron emission tomography scanning appears to be effective in detecting and following the progression of recurrent lung cancer. Retreatment of patients with asymptomatic recurrent tumor has resulted in absent or decreased FDG activity. Monitoring of patients with PET may provide prolonged survival in patients who otherwise would fail treatment because of local tumor recurrence.

Adenocarcinoma↗
PubMed1995

Recombinant Desulfovibrio vulgaris rubrerythrin. Isolation and characterization of the diiron domain.

The gene encoding Desulfovibrio (D.) vulgaris rubrerythrin (Prickril, B. C., Kurtz, D. M., Jr., LeGall, J., & Voordouw, G. (1991) Biochemistry 30, 1118), a protein of unknown function containing both FeS4 and (mu-oxo)diiron sites, was cloned and overexpressed in Escherichia coli. Upon cell lysis, the overexpressed protein was found in an insoluble form deficient in iron. Iron was incorporated in vitro by dissolving the protein in 3 M guanidinium chloride, adding Fe(II) anaerobically and diluting the denaturant. This recombinant rubrerythrin was found to have properties very similar to those of rubrerythrin isolated from D. vulgaris, except that the recombinant rubrerythrin contained six rather than four (or five) iron atoms per 44 kDa homodimer. Analyses of UV-vis, Mössbauer, and EPR spectra showed that the six iron atoms in recombinant rubrerythrin are organized as two FeS4 and two (mu-oxo/hydroxo)diiron sites. In order to allow examination of the diiron sites in the absence of the FeS4 sites, a truncated gene encoding the N-terminal 152 residues of D. vulgaris rubrerythrin was also cloned and overexpressed as an insoluble protein in E. coli, and iron was incorporated by a procedure analogous to that for recombinant rubrerythrin. This so-called "chopped" rubrerythrin (CRr) was found to consist of an approximately 35 kDa homodimer containing four iron atoms. Spectroscopic characterization indicated that the four iron atoms in CRr are organized as two diiron sites, the majority of which closely resemble the (mu-oxo)diiron(III) sites in E. coli ribonucleotide reductase R2 protein, and a minor fraction of which resemble the mixed-valent diiron(II,III) site in methane monooxygenase hydroxylase.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗
PubMed1995

Angiodysplasia of the lower gastrointestinal tract: an entity readily diagnosed by colonoscopy and primarily managed nonoperatively.

BACKGROUND: The characteristics of patients who develop clinically significant angiodysplasia of the lower gastrointestinal (GI) tract are unknown, and methods of treatment are evolving. PURPOSE: This study was undertaken to identify patient characteristics, methods of diagnosis, and current management of patients who require operation and outcome. METHODS: Patients with the diagnosis of angiodysplasia of the lower GI tract at St. Louis University affiliated hospitals over the past five years were reviewed. RESULTS: Thirty-two consecutive patients were identified. The mean age was 69.8 (range, 29-86) years; 62.5 percent were males. Patient characteristics included: age greater than 65 years, 22 of 32 patients (69 percent); documented coagulopathy, 9 of 32 patients (28 percent); and cardiac valvular disease, 8 of 32 patients (25 percent). Diagnosis was established by colonoscopy in 27 of 32 patients (84 percent), enteroscopy in 3 of 32 patients (9 percent), and angiography in 2 of 32 patients (6 percent). Seventy-eight percent of the angiodysplasias were located in the right colon. Patients were treated by endoscopic coagulation in 16 of 32 patients (50 percent), surgical resection in 9 of 32 (12.5 percent), or observation in 3 of 32 patients (9 percent). Four of 32 patients (12.5 percent) developed recurrent bleeding. Four of 32 patients (12.5 percent) died of various causes. FOLLOW-UP: Follow-up was possible in 25 of 28 surviving patients, and the follow-up period ranged from 3 to 42 months, during which rebleeding occurred in 5 patients who had been previously treated by endoscopic coagulation and in 1 patient who had been treated by transfusion alone. Two patients died of unrelated causes and one from a recurrent lower GI bleed. CONCLUSION: Angiodysplasia is primarily a disease of elderly patients. These patients are frequently anticoagulated and often have co-existing cardiac valvular disease. Endoscopy usually establishes the diagnosis, and endoscopic coagulation is an effective and safe method of treatment. Most patients can be managed without operation.

Adult↗
PubMed1995

An expression for the RBE of neutrons as a function of neutron energy.

The goal of this paper is to develop a relationship between a neutron RBE and neutron energy, En, which can be used to design neutron sources for BNCT. In an earlier calculation of a neutron RBE as a function of En, we approximated the contribution to a total neutron RBE, RBEt (En), arising from 14N(n,p)14C reactions. In this paper, we recalculate RBEt (En), accounting more exactly for the contribution to RBEt (En) from 14N(n,p)14C reactions.

Animals↗
PubMed1995

Vitamin D status in primary hyperparathyroidism in India.

OBJECTIVES: Primary hyperparathyroidism is a syndrome with variable clinical expression, presenting as asymptomatic hypercalcaemia in Western countries and with predominant bone disease in developing countries. Vitamin D deficiency has been implicated as the cause of bone disease. There is a paucity of information on the vitamin D (25-OHD3) status of patients with primary hyperparathyroidism presenting with bone disease. The present study aims to evaluate the vitamin D status in patients with primary hyperparathyroidism and to correlate it with the bone disease. DESIGN: Twenty consecutive patients with primary hyperparathyroidism admitted to the endocrinology and metabolism wards of the All India Institute of Medical Sciences were analysed to assess their clinical, radiological and biochemical features, as well as parathyroid hormone (mid-molecular, PTH-MM) and 25-OHD3 levels. MEASUREMENTS: PTH-MM levels and 25-OHD3 levels were measured using RIA kits. RESULTS: Bone disease (osteitis fibrosa cystica) was the mode of presentation in 90%. Radiologically, sub-periosteal resorption was present in 90% of the total group of patients, brown tumours in 60%, and pathological fractures in 40%. Renal stones and/or nephrocalcinosis was present in 50% of patients. Mean serum calcium, phosphate and alkaline phosphatase concentrations (mean of 3 days values) were 2.72 +/- 0.24 mmol/l; 1.01 +/- 0.28 mmol/l and 425 +/- 249 IU/l respectively. The 24-hour (mean of 3 days values) urine calcium and phosphate excretions were 8.0 +/- 4.2 mmol and 19.0 +/- 13 mmol. Only 50% of the patients had hypercalcaemia ( > 2.7 mmol/l). However, 90% of the whole group of patients had hypercalciuria. The mean serum creatinine concentration of patients with hypercalcaemia was 108 +/- 38 mumol/l and of those with normocalcaemia 89 +/- 33 mumol/l. The mean serum PTH-MM was 438 +/- 350 pmol/l (the detection limit for the kit was 34 pmol/l). Ultrasound examination detected adenomas in 72% of the cases and computerized tomography of the neck localized adenomas in 71% of the cases. The median weight of the adenoma was 4.6 g (range 0.125-25 g). Two patients had coexistent hyperplasia of the other parathyroid glands and two had recurrent adenomas. 25-OHD3 levels were assessed in all 20 patients under fasting conditions. The mean value of 25-OHD3 observed (8.4 +/- 5.1 micrograms/l) was comparable to the mean value measured in 14 healthy age and sex matched controls (8.3 +/- 2.5 micrograms/l). CONCLUSION: Patients with primary hyperparathyroidism in India presented with bone and renal diseases; half were normocalcaemic. All the patients had hypercalciuria despite the bone disease. The PTH-MM levels were increased and 25-OHD3 levels were low. The predominant bone disease is probably due to prolonged primary hyperparathyroidism coexisting with low calcium intake and/or 25-OHD3 deficiency. The mean weight of the adenoma was higher than that reported for patients in the Western literature.

Adenoma↗
PubMed1995

Immunochemical characterization of rapid and slowly released allergens from the pollen of Parthenium hysterophorus.

Allergens from the pollen of Parthenium hysterophorus (American feverfew), responsible for high incidence of allergic rhinitis, were found by immunoprint analysis to be localized on the surface of the pollen grains. The allergens were released very rapidly when extracted in vitro. The allergenic activity of the rapid (10 s) and slowly (20 h) released pollen proteins was comparable by in vivo skin test and ELISA inhibition assay. The isoelectric focusing patterns of the rapid and slowly released proteins were also identical. SDS-PAGE and Western blot analysis revealed that all the major pollen allergens with molecular weight 14, 28, 31, 37 and 45 kDa were eluted within 10 s of extraction. Periodate-Schiff staining showed that the 28, 31 and 45 kDa components of the pollen extract are glycoproteins. The pollen allergens released after different periods of extraction lost 75% of IgE binding activity when subjected to in situ sodium m-periodate oxidation under controlled conditions, while 80% of the allergenic activity was still retained after extensive proteolysis. Our results support the clinical observation of a rapid onset of symptoms of allergic rhinitis in patients sensitive to Parthenium pollen, mediated predominantly by glycoproteins.

Allergens↗
PubMed1994

Identification of frequent novel genetic alterations in small cell lung carcinoma.

We have performed a comprehensive analysis of the DNA copy number changes that occur in 18 small cell lung carcinoma cell lines using comparative genomic hybridization (Kallioniemi et al., Science (Washington DC). 258: 818-821, 1992). DNA copy number abnormalities detected in this study include previously identified increases at 1p22-32 (L-myc), 2p24-25 (N-myc), and 8q24 (c-myc) and decreases at 17p13 (p53), 13q14 (RB), and 3p. In addition, novel DNA copy number increases were detected at 5p, 1q24, and Xq26, and novel decreases were found at 22q12.1-13.1, 10q26, and 16p11.2. Many of the most common DNA copy number changes revealed are at loci not previously recognized to be important in small cell lung cancer. In addition, a number of the DNA copy number changes, including increases at 1p22-32, 2p24-25, and 3q22-25 and a decrease on 18p, were found to occur preferentially in small cell lung carcinoma lines of the "variant" phenotype. This correlation suggests that genes may reside at these loci whose overexpression or inactivation contributes to the radiation resistance or aggressive growth phenotypes characteristic of this subtype of small cell lung carcinoma.

Carcinoma, Small Cell↗
PubMed1994

Dose prescription in boron neutron capture therapy.

PURPOSE: The purpose of this paper is to address some aspects of the many considerations that need to go into a dose prescription in boron neutron capture therapy (BNCT) for brain tumors; and to describe some methods to incorporate knowledge from animal studies and other experiments into the process of dose prescription. MATERIALS AND METHODS: Previously, an algorithm to estimate the normal tissue tolerance to mixed high and low linear energy transfer (LET) radiations in BNCT was proposed. We have developed mathematical formulations and computational methods to represent this algorithm. Generalized models to fit the central axis dose rate components for an epithermal neutron field were also developed. These formulations and beam fitting models were programmed into spreadsheets to simulate two treatment techniques which are expected to be used in BCNT: a two-field bilateral scheme and a single-field treatment scheme. Parameters in these spreadsheets can be varied to represent the fractionation scheme used, the 10B microdistribution in normal tissue, and the ratio of 10B in tumor to normal tissue. Most of these factors have to be determined for a given neutron field and 10B compound combination from large animal studies. The spreadsheets have been programmed to integrate all of the treatment-related information and calculate the location along the central axis where the normal tissue tolerance is exceeded first. This information is then used to compute the maximum treatment time allowable and the maximum tumor dose that may be delivered for a given BNCT treatment. RESULTS AND CONCLUSION: The effect of different treatment variables on the treatment time and tumor dose has been shown to be very significant. It has also been shown that the location of Dmax shifts significantly, depending on some of the treatment variables--mainly the fractionation scheme used. These results further emphasize the fact that dose prescription in BNCT is very complicated and nonintuitive. The physician prescribing the dose would need to rely on some method, like the one developed here, to come up with an appropriate dose prescription.

Boron Neutron Capture Therapy↗
PubMed1994

Management of giardiasis by an immuno-modulatory herbal drug Pippali rasayana.

Pippali rasayana (PR), an Ayurvedic herbal medicine, prepared from Piper longum (Pippali) and Butea monosperma (Palash), and prescribed for the treatment of chronic dysentery and worm infestations was tested for anti-giardial and immuno-stimulatory activity in mice, infected with Giardia lamblia trophozoites. It produced up to 98% recovery from the infection. The rasayana had no killing effect on the parasite in vitro. It induced significant activation of macrophages as evidenced by increased macrophage migration index (MMI) and phagocytic activity. Enhancement of host resistance could be one of the possible mechanisms contributing towards the recovery of animals from the giardial infection.

Adjuvants, Immunologic↗
PubMed1994

Muscarinic receptor M1 and M2 subtypes in the human eye: QNB, pirenzipine, oxotremorine, and AFDX-116 in vitro autoradiography.

Muscarinic cholinergic agents are used to lower intraocular pressure in the medical management of glaucoma and subtypes of muscarinic receptors have now been recognised in many tissues including the eye. To localise muscarinic receptors and their M1 and M2 subtypes in the human eye, in vitro ligand binding and autoradiographic techniques with densitometric quantitation on postmortem eye sections were used. As ligands, [3H] quinuclydinyl benzylate (QNB) (non-subtype specific muscarinic antagonist), [3H]pirenzipine (M1 antagonist), [3H]oxotremorine (M2 muscarinic agonist), [3H]AFDX-116(11[(2[diethylaminomethyl]1-piperidinyl)acetyl]5 , 11dihydro-6H-pyrido [2,3b][1,4]benzodiazepine-6-one) (M2 antagonist) were studied. Specific binding sites for QNB, pirenzipine, and AFDX-116 were localised in the entire ciliary muscle, the iris, and ciliary epithelium. [3H]oxotremorine localised only in the longitudinal portion of the ciliary muscle, and additionally, was not localised in the iris or ciliary epithelium. These results suggest that oxotremorine, by binding selectively to receptors on the longitudinal ciliary muscle and inducing its contraction, may modulate outflow facility independently from accommodation and miosis.

Adult↗
PubMed1994

Localization of M3 muscarinic receptor subtype and mRNA in the human eye.

Cholinergic agents used to lower intraocular pressure in the medical management of glaucoma act on muscarinic receptors in the eye. Recently, subtypes of muscarinic receptors have been recognized in many tissues including the eye. To localize the M3 muscarinic receptor subtype and m3 messenger RNA (mRNA) in the human eye, we used in vitro ligand binding and in situ hybridization techniques on post-mortem sections. We used an M3 antagonist, [3H]-4-DAMP ([3H]-4-diphenylacetoxy-N-methylpiperidine methiodide) to identify M3-binding sites and a [35S]-labelled oligonucleotide probe to detect and localize m3 mRNA. M3 and m3 mRNA were both localized in the ciliary muscle, ciliary epithelium, iris, corneal epithelium and anterior lens epithelium. The m3 transcript was also detected in the trabecular meshwork and corneal endothelium.

Acetylcholine↗
PubMed1993

Further observations on MDT blister-calendar packs in vertical leprosy eradication programmes--a multicentre study (phase II)

To improve operational efficiency as well as to improve patient compliance in leprosy programmes, DANIDA introduced blister-calendar packs (BCP) to deliver MDT in 4 MDT districts in India in 1987. An objective study (Phase II) involving 343 patients in a trial group (BCP group) and 253 patients in a control group (loose drug group) showed no significant difference in compliance rates for self-administered dose between the 2 groups. Hence, while assessing the use of BCPs in leprosy programmes, other operational benefits like safe storage, easy transportation, easy drug accounting and safe preservation at home are to be considered. These aspects were followed up from Phase I of the study.

Adolescent↗
PubMed1993

Frusemide--digitalis interaction on experimental model.

Interaction of frusemide and digitalis on frog heart has been studied. It was found that like digitalis, frusemide did not have any effect on normal heart, but restored the normal myocardial contraction of the hypodynamic frog heart. Frusemide induced cardiac arrest when administered during digoxin infusion. It is suggested that interaction of frusemide and digoxin has additive effect.

Animals↗