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Biomedical subjects

N K Gupta

Publications and source records attributed to N K Gupta.

At least 37 records · Page 2Linked to original sources

Radical external beam radiotherapy for 333 squamous carcinomas of the oral cavity--evaluation of late morbidity and a watch policy for the clinically negative neck.

BACKGROUND AND PURPOSE: The aims of this study were to examine local control/morbidity for all cases and a 'watch policy' for the node-negative neck. PATIENTS/METHODS: 333 patients with squamous cell carcinoma of the oral cavity were treated with a short radical radiotherapy regime to the primary site and involved lymph node groups at the Christie Hospital, Manchester, between 1980 and 1987. Only 10 of 278 node-negative patients received elective neck node irradiation. RESULTS: Actuarial cancer-free survival and local control rates at 5 years for the whole group were 55% and 61%, respectively. Control at the primary site was adversely related to increasing T-stage, node positivity and bone involvement at presentation. Osteonecrosis was seen in 14 (5.9%) of 237 cases without bone involvement at presentation. Taking all patients, late morbidity (non-healing soft tissue injury or bone necrosis) was seen in 45 patients (13.6%) at a median time of 21 months from treatment. The factors contributing to late morbidity were: (1) bone involvement at presentation, (2) synchronous MTX chemotherapy, (3) the contribution of scattered radiation from elective neck treatment, (4) increasing radiation dose, (5) increasing target volume for doses less than 55 Gy and (6) dental extractions. Eighty-four (31%) patients who were initially node-negative developed disease in the untreated neck during follow-up. Salvage neck dissections controlled neck disease in half of the node-only recurrences (21/42 cases). CONCLUSION: These results have influenced our treatment policy, with lowering of the primary tumour dose in some cases and addition of elective neck irradiation for T2-T4 No patients.

Antimetabolites, Antineoplastic↗

Slow bolus injection of ribose in the identification of thallium-201 redistribution following combined adenosine/dynamic exercise stress.

AIM: A simple stress/redistribution thallium-201 myocardial perfusion imaging protocol may underestimate the degree of thallium redistribution in a defect identified on the stress images. We sought to investigate whether a slow-bolus injection of D-ribose improves the identification of thallium redistribution following combined adenosine/dynamic exercise stress. MATERIALS AND METHODS: Fifteen patients (10 males, five female, median age 63 years, range 50-75) were enrolled in the study. All underwent two successive adenosine plus exercise myocardial perfusion scintigraphy protocols 7-14 days apart. Adenosine was infused at 140 micrograms.kg-1.min-1 coupled with 25 W ergometer pedalling for 6 min with 74 Mbq of thallium-201 being injected at 4 min. Immediately following the stress image acquisition, patients received the one of either 60 mg.kg-1 of D-ribose or normal saline, injected over 5 min. Redistribution images were acquired after 4 h. The identical stress procedure was conducted in the crossover arm of the study, and patients received the alternative test article. SPECT images were visually analysed and scored in a nine segment model by two blinded observers. In addition, circumferential profile analysis was conducted. RESULTS: By visual interpretation 25 segments displayed redistribution of the ribose, but not in the saline study, 14 reversible segments were seen on the saline study alone and 18 were seen on both studies (P = ns). In six patients ribose identified a greater number of redistributing segments and in a further six patients saline identified more reversible segments. Comparison of mean values of defect extent severity and percentage reversibility scores generated from the circumferential profile analysis showed no significant difference between the two arms of the study. CONCLUSION: A 5 min bolus injection of D-ribose following combined adenosine/dynamic exercise stress confers little benefit on the identification of redistribution of thallium-201. These results differ from those of previous studies which showed that a 30 min infusion of D-ribose following treadmill exercise significantly enhanced thallium redistribution. The duration of the ribose infusion is likely to be an important factor influencing the effect brought to bear on the redistribution of the tracer, and should be run over 30 min, or longer.

Adenosine↗

Primary lymphoma of the skull presenting as multiple cranial nerve palsies.

Lymphoma presenting with isolated diffuse infiltration of the skull is exceedingly rare, with less than 20 previously reported cases. The clinical presentation of a 73-year-old female with primary lymphoma of the skull, manifesting multiple cranial nerve palsies and infiltration of the temporalis muscles is described. MRI of the head, revealed an abnormal signal from the diploic space of the call varium and skull base on both T1 and T2 weighted images, infiltration of the temporalis muscles and clivus, and diffuse meningeal enhancement encroaching on the cavernous sinus bilaterally. Biopsy of temporalis muscle and skull showed a diffuse large cell lymphoma, B-cell type. Staging workup failed to reveal any other sites of disease. Despite multiple cranial nerve palsies, there was no evidence of leptomeningeal disease on CSF examination. MRI was instrumental in demonstrating the abnormalities that lead to the diagnostic biopsy.

Aged↗

Myocardial perfusion scintigraphy in patients undergoing major non-vascular abdominal surgery.

The prognostic value of myocardial perfusion scintigraphy is beginning to be recognised in patients undergoing cardiovascular surgery. The aim of this prospective study was to assess the predictive value of scintigraphy in elderly patients undergoing major non-vascular abdominal surgery. Adenosine stress thallium-201 (201Tl) single-photon emission tomography (SPET) was employed for imaging using a standard protocol. Patients over the age of 60 years (n = 55) with an intermediate to high likelihood of coronary artery disease were evaluated prospectively. The clinical outcome variables analysed were cardiac mortality and major cardiac morbidity occurring within 30 days of surgery. Cardiac events were cardiac death (n = 5), angina pectoris (n = 5), nonfatal mycardial infarction (n = 1), acute left ventricular failure (n = 2) and arrhythmias requiring treatment (n = 4). All cardiac events occurred in the first 10 postoperative days except one cardiac death which happened on the 29th postoperative day. Patients with an abnormal 201Tl SPET scan had a higher risk of postoperative death (4 vs 1) or any postoperative cardiac event (13 patients vs 4 patients; P < 0.0001) when compared with those with a normal scan. The sensitivity, specificity and positive predictive value of 201Tl imaging for perioperative ischaemia and adverse outcomes were 76%, 82% and 65%, respectively. The occurrence of an intraoperative event (P < 0.02) and the length of surgery (P < 0.01) were also predictors of a postoperative cardiac event. Clinical risk variables and an abnormal electrocardiogram in isolation were poor predictors. In conclusion, preoperative myocardial perfusion scintigraphy is a valuable technique for identifying elderly patients with a high risk for cardiac events when undergoing major non-vascular abdominal surgery.

Abdomen↗

Olfactory neural tumours--the role of external beam radiotherapy.

Olfactory neuroblastoma is an uncommon tumour arising in the nasal cavity or paranasal sinuses. We report the management of nine cases treated with external beam radiotherapy subsequent to surgery, either attempted definitive removal or biopsy only. Recent refinements in pathological evaluation of these tumours are discussed. Seven cases were deemed classical olfactory neuroblastoma whilst two were classified as neuroendocrine carcinoma. The clinical features, radiotherapy technique and variable natural history are presented. Seven of eight patients treated radically were controlled locally, with a minimum follow-up of two years. Three patients developed cervical lymph node disease and three patients died of systemic metastatic disease. Suggestions are made as to which patients should have en-bloc resection rather than definitive radiotherapy.

Aged↗

Modification of radiation induced changes in murine hepatic lipid profiles by garlic (Allium sativum Linn.) unsaturated oils.

Adult male Swiss albino mice were administered 74 kBq g-1 body weight of 45Ca in the presence and absence of garlic unsaturated oils, and the changes in total lipids, triglycerides, phospholipids and free fatty acids contents of liver were observed at various intervals from 1 to 14 days post-treatment. The results obtained indicate that garlic oils prevented rapid increase in hepatic total lipids, triglycerides and phospholipids and decrease in free fatty acids induced by radiocalcium and the values reached normal values earlier in garlic treated animals than in irradiated animals. Possible mechanism underlying the protective action of garlic oils is reported.

Allyl Compounds↗

Technetium-99m-L,L-ethylenedicysteine scintigraphy in patients with renal disorders.

Technetium-99m-L,L-ethylenedicysteine (99mTc-L,L-EC), a new renal imaging agent, was introduced as an alternative to 99mTc-mercaptoacetyltriglycine (MAG3). This radiopharmaceutical can be easily labelled at room temperature and has high radiochemical purity and long stability. The aim of this study was to gain clinical experience in using 99mTc-L,L-EC in normal volunteers and patients. The clearance of this radiopharmaceutical was compared with that of iodine-131 ortho-iodohippurate (OIH) in five healthy volunteers. In addition, conventional renogram and whole-body distribution of 99mTc-L,L-EC (40 min and 3 h post-injection) were evaluated in these subjects. Subsequently, ten patients with suspected obstructive nephropathy, four with renovascular disorders and two in acute renal failure were imaged. In five patients with impaired renal function both 99mTc-MAG3 and 99mTc-L,L-EC studies were performed. In each case the scintigraphic images and time/activity curves were evaluated and various semiquantitative parameters calculated and compared. No adverse effects were noted during and after 99mTc-L,L-EC scintigraphy. The mean clearance values for 99mTc-L,L-EC and 131I-OIH in volunteers were 504 and 663 ml/min respectively. The total plasma clearance of 99mTc-L,L-EC was about 75.8% of the 131I-OIH value. In volunteers the parenchymal transit time index, whole kidney transit time index and mean parenchymal transit time for 99mTc-L,L-EC were 63 s, 124 s and 175 s respectively. The mean time to peak activity was 235 s and the time from peak to 50% of peak activity was 402 s.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

An analysis of radiotherapy in the management of 104 patients with parotid carcinoma.

A retrospective analysis was made of 104 patients with parotid carcinoma treated with radical radiotherapy between 1977 and 1986. Eighty-seven patients received postoperative radiotherapy and 17 had radiotherapy alone. The 5- and 10-year survival figures, corrected for intercurrent deaths, were 60% and 49% respectively, with primary control rates of 68% and 58%. Local control was significantly better for patients initially presenting with T1/T2 disease, but local relapse still occurred in 23% of these patients. Of 13 patients with acinic cell tumours, four developed local recurrence and a further two had metastatic disease. These patterns of relapse suggest that patients with parotid carcinoma should receive postoperative radiotherapy irrespective of disease stage or histological type.

Adolescent↗

Impaired thermoregulation in Raynaud's phenomenon.

UNLABELLED: In an attempt to examine the role of the thermoregulatory apparatus in the etiology of Raynaud's phenomenon (RP), the authors exposed 15 women with RP and 12 controls to central body cooling and central body warming. Subjects were placed in an environmental chamber at 25 degrees C. Their right hand was placed in an annex of the chamber, which was insulated from the main chamber and maintained at a constant temperature of 25 degrees C throughout the experiment. Blood flow was measured in the digits of the right hand by venous occlusion strain gauge plethysmography and skin thermometry. Body temperature was measured with an oral thermometer. The temperature of the chamber was then increased to 35 degrees C and then reduced to 13 degrees C for twenty-five minutes with measurements repeated. Following this period patients were rewarmed in an ambient temperature of 35 degrees C for twenty minutes. RESULTS: subjects with RP had significantly lower blood flow at all stages of the test; moreover, their digital rewarming response following central cooling was considerably prolonged when compared with controls. Body temperature was lower and dropped significantly more in the RP group following the cold challenge. The authors conclude that subjects with RP have an impaired thermoregulatory mechanism. This may partially explain cold sensitivity.

Adult↗

Combined rest thallium-201/stress technetium-99m-tetrofosmin SPECT: feasibility and diagnostic accuracy of a 90-minute protocol.

UNLABELLED: Technetium-99m tetrofosmin is a recently developed compound that clears from background organs rapidly. Tetrofosmin has a good correlation with 201Tl. This study assesses the feasibility and diagnostic accuracy of a combined protocol involving rest 201Tl SPECT and stress imaging with 99mTc-tetrofosmin. METHODS: Twenty-five patients (23 men, 2 women; aged 36-73 yr) with known coronary artery disease underwent the combined protocol. Twenty minutes after the resting injection of 201Tl, resting SPECT data were acquired using low-energy, high-resolution collimators. A stress test using adenosine infusion combined with low-level dynamic exercise was performed. The stress data were collected 20 min later. The reconstructed vertical long-axis, horizontal long-axis and short-axis slices were analyzed qualitatively. Analysis was carried out using nine segments of the left ventricle. The segments were reported either as fixed or reversible. The results were compared to coronary angiography results. RESULTS: The sensitivity and specificity for the detection of diseased coronary vessels were 85% and 70% for the left anterior descending territory, respectively, 78% and 71% for the right coronary artery, and 69% and 70% for the left circumflex. Overall, the sensitivity was 80% and the specificity 70%. CONCLUSION: Combined rest 201Tl/stress 99mTc-tetrofosmin SPECT provides a protocol of short duration which displays similar diagnostic accuracy to a protocol using tetrofosmin as a single agent.

Adult↗

Regulation of an eukaryotic initiation factor-2 (eIF-2) associated 67 kDa glycoprotein (p67) and its requirement in protein synthesis.

The p67 mRNA level and p67 requirement in protein synthesis were studied using an animal cell (KRC-7, rat tumor hepatoma cell) in culture. p67 mRNA was present in confluent cells but disappeared almost completely from serum-starved cells. However, when PMA was added to the serum-starved cells, p67 mRNA appeared in increasing quantities. Several-fold molar excess of p67 mRNA over that present in confluent cells was detected within 2 h of PMA addition and this level remained the same during the 4 h of the experiment. p67 requirement in protein synthesis was studied using a p67 antisense DNA construct under a metallothionein gene promoter. Expression of this antisense DNA in the presence of zinc in PMA-induced serum-starved cells completely inhibited induced appearance of p67 mRNA and subsequent protein synthesis. These results suggest that p67 is regulated at the mRNA level and also that this protein factor is essential for protein synthesis.

Aminopeptidases↗

Thermodynamic characterization of the cooperativity of 40S complex formation during the initiation of eukaryotic protein synthesis.

The first step in mammalian protein synthesis is the formation of the 40S initiation complex, composed of the 40S ribosomal subunit (R), mRNA (M, here, a 10-mer oligoribonucleotide analogue containing the initiation codon), and the quaternary complex (Q, composed of eIF-2, GTP, Met-tRNA(fMet), and the ancillary protein factor Co-eIF-2C). The interdependence of the binding of R, M, and Q in forming the 40S complex is currently unclear. We have determined the thermodynamic parameters that characterize these interactions. The binary constants for R+M and Q+M were determined spectroscopically, measuring changes in the anisotropy of the fluorescence emission of 3'-fluorescein labeled M. The other binary constant, for Q+R, and the ternary constant were determined from Millipore filtration assays using radiolabeled Met-tRNA(fMet). The association constants for the binary reactions were as follows: Ka(Q,M) < or = 0.14 x 10(6) M-1, Ka(R,M) = 1.78 x 10(6) M-1, and Ka(Q,R) = 0.94 x 10(6) M-1. The binding of Q to R.M was markedly greater than that of Q to R [Ka(Q,R.M)/Ka(Q,R) > 62]. High cooperativity for this interaction occurs in either a single-site model or in lattice models for the binding of M to R. Data obtained using five other RNA 10-mers, each with the sequence altered at the AUG codon, suggest that this cooperativity is AUG dependent. The data are consistent with a scheme in which mRNA and Q bind independently to the 40S ribosome, but when the AUG codon is properly aligned with Q, a conformational change results in a 2.4 kcal/mol stabilization of the complex.

Animals↗

Regulation of eIF-2 alpha-subunit phosphorylation in reticulocyte lysate.

An eIF-2 associated 67-kDa protein (p67) protects eIF-2 alpha-subunit from eIF-2 kinase(s) catalyzed phosphorylation and promotes protein synthesis in the presence of active eIF-2 kinase(s). p67 is a glycoprotein and contains multiple O-linked GlcNAc moieties. We have now studied the roles of hemin, p67, and the glycosyl residues on p67 in the regulation of eIF-2 alpha-subunit phosphorylation in reticulocyte lysates. The results are as follows: (i) Both hemin and p67 inhibited HRI (heme-regulated protein synthesis inhibitor) and dsI (double-stranded RNA activated protein synthesis inhibitor) catalyzed phosphorylation of eIF-2 alpha-subunit in vitro. However, only hemin, and not p67, inhibited casein kinase catalyzed phosphorylation of eIF-2 beta-subunit. (ii) Only p67, and not hemin, inhibited eIF-2 alpha-subunit phosphorylation by eIF-2 kinase(s) in reticulocyte lysate. Significant eIF-2 alpha-subunit phosphorylation was observed even in the presence of hemin when p67 in the reticulocyte lysate was removed by treatment with p67 antibodies. (iii) Reticulocyte lysate contains a p67-deglycosylase in latent form, and hemin prevents activation of this deglycosylase. In the absence of hemin, this p67-deglycosylase is activated. Once activated in the absence of hemin, the activated deglycosylase deglycosylates p67, even in the presence of hemin. This inactivates p67 and allows eIF-2 kinase to phosphorylate eIF-2 alpha-subunit and inhibit protein synthesis. Protein synthesis in reticulocyte lysate is thus regulated by two novel cascades of covalent modifications: protein deglycosylation leading to protein phosphorylation.

Acetylglucosaminidase↗

Angioscopy-guided training model of coronary artery anastomosis.

Surgical models are proving invaluable in the training of junior surgeons or in the development of new skills by senior surgeons. We have developed a model in which coronary artery anastomoses may be performed and evaluated with an angioscope, thus facilitating development of skills.

Angioscopy↗

Fate of patients with residual tumour at the bronchial resection margin.

The presence of microscopic deposits of tumour cells at the bronchial resection margin (BRM) may adversely affect the prognosis of patients. Residual tumour cells were identified at the BRM in 40 (5.4%) of 735 patients who had been operated on for non-small cell lung carcinoma (NSCLC). The extent of disease was stage I in 7 (17.5%), stage II in 21 (52.5%), stage IIIa in 10 (25%) and stage IIIb in 2 (5%) patients. Malignant cells were found to have infiltrated the submucosal lymphatics in 5 (12.5%) cases and the peribronchial tissue in the remaining 35 (87.5%). Fifteen (37.5%) patients received adjuvant radiotherapy (RT). Recurrence of the disease was diagnosed in 29 (72.5%) patients after a median of 17 months (range 3-111). The recurrence was local in 17 (59%) and distant in 12 (41%). The 5-year overall actuarial survival rate was 21.6% and was not affected by RT (P = NS). Only patients with stage IIIa disease and a positive bronchial stump had a significantly reduced 5-year survival rate compared to those with a negative stump, 0% vs 17% (P < 0.001). Tumour cells at the resection margin did not affect the survival in this cohort except those with stage IIIa disease, and the addition of adjuvant RT did not significantly affect its recurrence in patients with NSCLC.

Aged↗