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Biomedical subjects

N Gupta

Publications and source records attributed to N Gupta.

At least 235 records · Page 13Linked to original sources

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↗

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↗

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↗

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↗

Verlukast (MK-0679) conjugation with glutathione by rat liver and kidney cytosols and excretion in the bile.

Verlukast (MK-0679) is a potent leukotriene D4 antagonist that was under development for the treatment of bronchial asthma. A previously uncharacterized metabolite of verlukast was formed in incubations using rat liver cytosol fortified with glutathione (GSH). The metabolite was detected by HPLC and characterized by UV spectroscopy (photodiode array detection after HPLC) and capillary HPLC continuous flow-liquid secondary-ion mass spectrometry. After a large-scale incubation and isolation, it was further characterized by 500 MHz proton NMR. The metabolite is a 1,4-Michael addition product in which GSH has added to position 12 of the styryl quinoline double bond of verlukast. There is no apparent stereoselectivity because a mixture of the two possible isomers, in equal amounts, was observed by NMR. Although there was spontaneous chemical addition of GSH to verlukast (0.18 nmol/min), the reaction was shown to be enzyme-catalyzed in studies using three different preparations of rat liver cytosol at pH 7.4. Using Lineweaver-Burk analysis of experiments in which the effect of verlukast concentration on the rate of conjugation was studied, the apparent KM and Vmax were determined to be 107 +/- 22 microM (SD, N=3) and 0.66 +/- 0.21 nmol/min/mg protein, respectively. In similar studies with GSH as the variable substrate, the apparent KM and Vmax were 2.32 +/- 0.68 mM and 0.69 +/- 0.14 nmol/min/mg protein, respectively. Incubations with kidney cytosol produced the GSH, cysteinylglycine, and cysteine conjugates of verlukast. In bile collected from rats dosed intravenously with 50 mg/kg of verlukast, approximately 80% of the dose was recovered up to 4 hr postdose. The GSH conjugate accounted for 16.5% of the dose. The cysteinylglycine, cysteine, and N-acetylcysteine conjugates were observed and together accounted for 7.5%. Verlukast accounted for 14.5%, and the remainder of the metabolites (40.5%) were oxidation or acyl glucuronide metabolites.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Breastfeeding and childhood cancer.

Total duration of breastfeeding and of exclusive breastfeeding was studied and compared in 99 childhood cancer cases and 90 controls. The difference between the average duration of breastfeeding in cases and controls was significant (p < 0.05), but when average duration of exclusive breastfeeding was compared in cases and controls the difference was highly significant (p < 0.001). In lymphoma cases and controls the difference between the average duration of breastfeeding was moderately significant (p < 0.01). However, when average duration of exclusive breastfeeding was compared in lymphoma cases and controls the difference was highly significant (p < 0.001). When other cancer groups and controls were compared with respect to their total duration of breastfeeding and duration of exclusive breastfeeding the differences when insignificant (p > 0.05). Cases and controls were not different with respect to their age, sex, birth year, birth order, age and educational status of mothers, smoking of fathers and socioeconomic status. However, a positive family history of cancer was obtained in 4 (4%) of cases whereas in controls it was obtained in only 1 (1.1%).

Adolescent↗

A highly specific heterologous enzyme-linked immunosorbent assay for measuring testosterone in plasma using antibody-coated immunoassay plates or polypropylene tubes.

A highly specific and sensitive enzyme-linked immunosorbent assay, using a heterologous combination of antiserum raised against testosterone-3-(O-carboxymethyl) oxime-bovine serum albumin and penicillinase-labeled testosterone-11 beta-carboxymethyl ether, was developed for measuring testosterone in human plasma. Immunoassay plates (96 wells) provided a sensitivity of 2.5 pg/well. This was achieved by maintaining the molar ratios of steroid to enzyme between 10 and 20. The assay was very specific for testosterone and did not show any cross-reaction with the related C19 steroids tested. Replacement of immunoassay plates with the locally available polypropylene tubes raised the detection limits to 25 pg/tube, but improved the range of doses of testosterone that could be measured up to 10,000 pg. The antiserum to testosterone derivative was linked to both immunoassay plates and polypropylene tubes through immunochemical bridges. Comparison of testosterone values of 52 plasma specimens obtained by both solid phase methods with those of radioimmunoassay showed good correlation.

Antibodies↗