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Biomedical subjects

N Nair

Publications and source records attributed to N Nair.

At least 19 recordsLinked to original sources
PubMed1999

Relative efficacy of 32P and 89Sr in palliation in skeletal metastases.

UNLABELLED: 32p and 89Sr have been shown to produce significant pain relief in patients with skeletal metastases from advanced cancer. Clinically significant pancytopenia has not been reported in doses up to 12 mCi (444 MBq) of either radionuclide. To date, no reports comparing the relative efficacy and toxicity of the two radionuclides in comparable patient populations have been available. Although a cure has not been reported, both treatments have achieved substantial pain relief. However, several studies have used semiquantitative measures such as "slight," "fair," "partial" and "dramatic" responses, which lend themselves to subjective bias. This report examines the responses to treatment with 32P or 89Sr by attempting a quantification of pain relief and quality of life using the patients as their own controls and compares toxicity in terms of hematological parameters. METHODS: Thirty-one patients with skeletal metastases were treated for pain relief with either 32P (16 patients) or 89Sr (15 patients). Inclusion criteria were pain from bone scan-positive sites above a subjective score of 5 of 10 despite analgesic therapy with narcotic or non-narcotic medication, limitation of movement related to the performance of routine daily activity and a predicted life expectancy of at least 4 mo. The patients had not had chemotherapy or radiotherapy during the previous 6 wk and had normal serum creatinine, white cell and platelet counts. 32P was given orally as a 12 mCi dose, and 89Sr was given intravenously as a 4 mCi (148 MBq) dose. The patients were monitored for 4 mo. RESULTS: Complete absence of pain was seen in 7 of 16 patients who were given 32P and in 7 of 15 patients who were given 89Sr. Pain scores fell by at least 50% of the pretreatment score in 14 of 16 patients who were given 32P and 14 of 15 patients who were given 89Sr. Mean duration of pain relief was 9.6 wk with 32P and 10 wk with 89Sr. Analgesic scores fell along with the drop in pain scores. A fall in total white cell, absolute granulocyte and platelet counts occurred in all patients. Subnormal values of white cells and platelets were seen in 5 and 7 patients, respectively, with 32P, and in 0 and 4 patients, respectively, after 89Sr therapy. The decrease in platelet count (but not absolute granulocyte count) was statistically significant when 32P patients were compared with 89Sr patients. However, in no instance did the fall in blood counts require treatment. Absolute granulocyte counts did not fall below 1000 in any patient. There was no significant difference between the two treatments in terms of either efficacy or toxicity. CONCLUSION: No justification has been found in this study for the recommendation of 89Sr over the considerably less expensive oral 32P for the palliation of skeletal pain from metastases of advanced cancer.

Administration, Oral↗
PubMed1998

Does renal damage occur after the administration of 32P for palliation of pain from skeletal metastases?

In normal adults, the maintenance of phosphate balance involves the reabsorption of 85-90% of filtered phosphate by the proximal tubule. At a glomerular filtration rate (GFR) of 125 ml min-1 and a plasma phosphate concentration of 1.3 mmol l-1, the filtered phosphate is approximately 235 mmol day-1. Following intravenous administration, 25-50% of 32P is excreted over 4-6 days in normal subjects. In spite of such extensive renal handling of phosphate and, therefore, of 32P, there are no data in the literature concerning possible 32P-related nephrotoxicity. Adult dosimetry values for the kidney after 32P are reported as 4.8 rad mCi-1 h-1 (0.048 mSev 37 MBq-1 h-1). The entry criteria for 32P therapy insist on a normal serum creatinine value, reflecting awareness of potential renal damage. To answer the fundamental question of whether there is demonstrable renal damage after 32P, we undertook serial measurements of GFR in patients given 32P for treatment of pain from skeletal metastases. Twenty-one patients who had normal pre-treatment renal function as shown by normal serum creatinine values were administered 32P orally in doses ranging from 277.5 to 466.2 MBq, with a mean of 425.5 MBq. Pre-treatment, GFR was estimated with 99Tcm-diethylenetriamine pentaacetate renography using the Gates protocol. Post-treatment, GFR was estimated serially as far as possible, at weeks, 1, 2, 3 and 4 and then every 4 weeks for another 3 months, at which point follow-up ceased. Serum creatinine was assessed pre-treatment and every 2 weeks until the end of follow-up, in addition to all other parameters and a clinical evaluation. Mean pre-treatment GFR was 87.5 ml min-1, with a range of 48.7-110 ml min-1. Not all patients could fulfil the entire follow-up schedule as designed, but we obtained a minimum of four follow-up tests, two before and two after 4 weeks post-treatment. GFR fell to 72% of the pre-therapy value during the first 4 weeks following therapy. By the sixteenth week, however, the mean value had returned to or exceeded the pre-treatment value. There was no change in serum creatinine values. At a time when multiple therapies are being considered, this early depression of GFR may be of importance. A closer assessment of altered renal function may be warranted and other sensitive tests of renal damage like microalbuminuria could be used.

Adult↗
PubMed1998

Zinc, copper and hydrolytic enzymes in epididymis of hydrocortisone treated rat.

Administration of glucocorticoid (1, 2 and 4 mg) in excess leads to degeneration of epididymides as supported by cellular degeneration, sperm density and morphometric measurements. Zinc level increased statistically after 1, 2 and 4 mg hydrocortisone treatment while copper increased after 1 and 2 mg treatment. Cholesterol, protein and leucine aminopeptidase levels increased and decreased significantly in caput and cauda respectively. Activity of alkaline phosphatase reduced significantly while the treatment of hydrocortisone at different doses elevated acid phosphatase, aryl sulphatase and lactate dehydrogenase activities. Evidently, these changes are as a result of onset of cellular degeneration leading to impairment of metabolic/secretory activity of epididymal cells. The possible involvement of pituitary-testis axis in hydrocortisone induced epididymal degeneration and functional inhibition has been discussed.

Acid Phosphatase↗
PubMed1996

Crisis intervention in a general hospital.

This paper presents the data of 90 patients admitted consecutively for crisis intervention in the psychiatric ward of the National University Hospital, Singapore. There were 48 men and 42 women; their mean age was 31.4 years (SD +/- 12.9). More women (73%) had relationship problems than men but more men (52%) had work related problems-the difference is significant (p < 0.01). The commonest diagnoses were depression (45%) and adjustment reaction (24%). The mean duration of hospitalisation was 4.3 days (SD +/- 2.3). The majority of patients (63%) were managed by supportive psychotherapy and the remaining 37% by supportive psychotherapy and medication. On follow up after one month, 20% of the sample were well, 62% improved and 18% were not better. About 85% of the sample could be contacted after 3 months, and of these, 51% were well, 39% improved but 10% were still not better. The efficacy of crisis intervention is briefly discussed.

Adolescent↗
PubMed1995

Effect of adrenalectomy and adrenalectomy+hydrocortisone treatment on histopathological, biochemical and zinc and copper profiles in rat testes.

Degenerative changes such as decreased seminiferous tubule diameter, Leydig cell nuclear diameter, spermatogenic arrest, oedematous fluid in the interstitium and lumen of seminiferous tubules and increased levels of zinc, copper and enzymes (lactate dehydrogenase, LDH; leucine aminopeptidase, LAP; and aryl sulphatase) in adrenalectomised rats suggest a possible role of adrenal cortex and its hormones in spermatogonial cell proliferation and subsequent differentiation, homeostasis of biological trace elements and behaviour of enzymes. Atrophy of Leydig cells and the degenerative changes in testes of adrenalectomised rats can be attributed to reduced supply of testosterone. Hydrocortisone, administered through a single dose acted as hyperstate of hydrocortisone for a short duration, thereby inhibiting steroidogenesis either directly by affecting Leydig cell testosterone production or indirectly by affecting the release of LH from pituitary gland and thus caused degeneration of germinal epithelium. Once hydrocortisone (half life < 12 hr) was metabolized, the animals returned to adrenalectomised state, the degeneration persisted. Thus, hydrocortisone administered through a single dose was insufficient to sustain spermatogenesis. Chronic administration at physiological dose may renew spermatogenesis. Increased levels of LDH, LAP and arylsulphatase are, probably, necessary for cellular degeneration. Zinc and copper exhibited an increase and the rise can be corroborated to (1) failure of regulatory mechanism(s) that control the flow of the elements across the blood-testes barrier; and (2) increased oedematous fluid formed by cellular deaths of the germinal epithelium.

Adrenal Cortex↗
PubMed1994

Neonatal screening for congenital hypothyroidism using the filter paper thyroxine technique.

A total of 25,244 full term consecutive newborns were screened for hypothyroidism at 24 to 96 h of birth using the filter paper technique for thyroxine. The screening protocol based on our pilot study considered filter paper thyroxine (FP-T4) values of 51 to 80 ng/ml (-1 SD) as borderline and < 50 ng/ml (-2 SD) as high risk for congenital hypothyroidism. FP-T4 and/or serum T4 and TSH were reestimated in all neonates with FP-T4 < 80 ng/ml. A total of 4775 (18.9%) newborns (FP-T4, 51 to 80 ng/ml in 4435 and < 50 ng/ml in 340) needed the recall; 2237 (50.4%) with FP-T4 51 to 80 ng/ml recalled by letters and 283 (83.3%) of the 340 subjects with FP-T4 < 50 ng/ml recalled by home visit, responded by 6 wk of age. Congenital hypothyroidism was confirmed in 6 newborns. FP-T4 in one persisted at 55 ng/ml on follow up and in the remainder both initial and repeat values were < 50 ng/ml. Follow up serum T4 values were subnormal (7.8-50.2 ng/ml) and serum TSH elevated (80-1233 IU/ml). Technetium thyroid scan showed agenesis in 3, ectopia in 2 and normal gland with probable dyshormonogenesis in one. Three other newborns (FP-T4 93 to 143 ng/ml) escaped primary detection and were referred later for congenital hypothyroidism. The incidence of congenital hypothyroidism by primary screening was 1:4207 (6 of 25,244) but with these 3 missed cases, probably 1:2804. Congenital hypothyroidism was reconfirmed in all 9 infants between the ages of 2 1/2 to 4 yr.(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital Hypothyroidism↗
PubMed1993

Selenium--its biological perspectives.

Selenium is an essential trace element at lower concentrations and toxic at higher concentration. Animals can metabolize both inorganic and organic forms and convert non methylated Se to mono--or di--or tri--methylated forms, of which, mono-methylated forms are most toxic. Glutathione reductase converts selenoglutathione to H2S in liver and erythrocytes and is ultimately excreted. Se effects the toxicities of xenobiotic agents, provides antagonistic effect to Sulphur and co-administration with Zn increase Se retention in certain organs. At its toxic level (4-8 ppm) it increases Cu contents of heart, liver and kidney and has detoxifying or protecting effect against Cd and Hg. It is a prosthetic group of several seleno metalloenzymes. The concentration of the element is decreased in serum/plasma or erythrocytes of patients of AIDS, trisomy-21, Crohn's and Down's syndrome, phenylketonurea, Keshan's disease and cancer. Rather, the element has antiproliferative and cancer protecting effect. Se content of testes increases considerably during pubertal maturation and, during Se deficiency, the supply to the testes has priority over the other tissues. The element is localized in the mitochondrial capsule protein (MCP) and is involved in biosynthesis of testosterone. Neither the age of mother nor the concentration of Se during pregnancy has any effect on weight of baby or the length of pregnancy. Se levels in human milk is affected by maternal intake and its requirements by infants and young children are higher for their rapid growth. Clinical symptoms of its toxicity include severe irritations of respiratory system, metallic taste in mouth, formication of nose, signs of rhinitis, lung edema and brancho-pneumonia. The typical garlic odour of breath and sweat is due to dimethyl-selenide.

Animals↗
PubMed1992

Increased oncogenic potential of ErbB is associated with the loss of a COOH-terminal domain serine phosphorylation site.

The erbB oncogene encodes an altered form of the epidermal growth factor (EGF) receptor that lacks the extracellular ligand binding domain. This oncogene is exclusively leukemogenic. However, an increase in oncogenic potential and a broadening of the tissue specificity of tumor formation occurs after retroviral transduction of erbB. The increased oncogenic potential correlates with structural alterations within the erbB gene. One common event is the deletion of a serine phosphorylation site located within the COOH-terminal domain. This site of phosphorylation has been demonstrated to be required for EGF-induced desensitization of signaling by the EGF receptor (Countaway, J. L., Nairn, A. C., and Davis, R.J. (1992) J. Biol. Chem. 267, 1129-1140). Here we show that the mutation of erbB at this negative regulatory serine phosphorylation site causes fibroblast transformation in vitro and is associated with an increased oncogenic potential in vivo.

3T3 Cells↗
PubMed1992

A comparison of moclobemide, amitriptyline and placebo in depression: a Canadian multicentre study.

In a 7-week prospective multicentre study, the efficacy, tolerability and safety of moclobemide were compared to those of amitriptyline and placebo in parallel groups of out-patients (n = 173) fulfilling the DSM III-R criteria for a major depressive episode. Participants were required to have a minimum baseline total score of 18 on the 17-item Hamilton Depression Rating Scale (HAMD). After a 1-week placebo washout, patients were randomly allocated to the three treatment groups. Assessment of efficacy, as judged by the number of responders achieving a 50% reduction in HAMD score by the end of treatment, showed that both moclobemide and amitriptyline were significantly superior to placebo, but that they were not significantly different from each other. Both treatments differed significantly from placebo with respect to the Physician's Global Assessment of Efficacy ('very good' or 'good' response: moclobemide 57%, amitriptyline 60% and placebo 35%). Assessment of tolerance as judged by the spontaneous reporting of adverse events showed a significant superiority of moclobemide over amitriptyline, but there was no significant difference between moclobemide and placebo. At termination of the study, amitriptyline patients showed a significant elevation of heart rate both supine (10.8 beats/min) and standing (15.5 beats/min), as well as significant weight gain (1.7 kg), but no changes were seen in the moclobemide or placebo groups. In conclusion, both moclobemide and amitriptyline were found to be more effective than placebo in the treatment of depression, while moclobemide had fewer side effects.

Adult↗
PubMed1992

Utility of technetium-t-butyl isonitrile (99mTc-TBI) myocardial imaging in coronary artery disease.

99mTc-t-butyl isonitrile is a useful agent for myocardial perfusion imaging. The superior physical advantages of technetium over 201thallium make larger doses possible for imaging. Accumulation in the myocardium is unidirectional in that once attached it does not leave the myocardium and hence two separate injections are needed for rest and stress imaging. High liver uptake frequently conceals the inferior wall and high early uptakes make immediate post-injection imaging almost impossible at least up to 45-60 min. This agent, however, was seen to accurately identify under-perfused areas and distinguish between ischaemia and infarct in our patients. Agreement with 201Tl and with GBP study of regional wall motion was excellent. While its individual sensitivity and specificity are quite high at 82.6 and 90.9%, in combined GBP studies the sensitivity rose to 93.4%. It is concluded that Tc-TBI is a valuable agent for myocardial perfusion scintigraphy, especially in a developing country like India where Tc-MIBI cannot be routinely used, since it is expensive, and where regular supplies of 201Tl are also not always feasible due to the high cost of importing. 99mTc-TBI can be made cheaply here and in a select population, notably in those with left anterior descending and circumflex coronary artery disease, it can provide valuable information.

Coronary Angiography↗
PubMed1992

Protein tyrosine kinase activities of the epidermal growth factor receptor and ErbB proteins: correlation of oncogenic activation with altered kinetics.

We have compared the protein tyrosine kinase activities of the chicken epidermal growth factor receptor (chEGFR) and three ErbB proteins to learn whether cancer-activating mutations affect the kinetics of kinase activity. In immune complex assays performed in the presence of 15 mM Mn2+, ErbB proteins and the chEGFR exhibited highly reproducible tyrosine kinase activity. Under these conditions, the ErbB and chEGFR proteins had similar apparent Km [Km(app)] values for ATP. The ErbB proteins appeared to be activated, as they had at least 3-fold-higher relative Vmax(app) for autophosphorylation and approximately 2-fold higher relative Vmax(app) for the phosphorylation of the exogenous substrate TK6 (a bacterially expressed fusion protein containing the C-terminal domain of the human EGFR). The ErbB kinases had both higher Km(app) and higher Vmax(app) for the phosphorylation of the exogenous substrate TK6 than did the chEGFR. The ratios of the Vmax(app) to the Km(app) for TK6 phosphorylation suggested that the ErbB proteins had lower catalytic efficiencies for the exogenous substrate than did the chEGFR. The three tested ErbB proteins had cytoplasmic domain mutations that conferred distinctive disease potentials. These mutations did not affect the kinetics for the phosphorylation of the exogenous substrate TK6. Two of the ErbB proteins contained all of the sites used for autophosphorylation. In these, a mutation that broadened oncogenic potential to endothelial cells caused an additional increase in Vmax(app) for autophosphorylation. Thus, mutations that change the EGFR into an ErbB oncogene cause multiple changes in the kinetics of protein tyrosine kinase activity.

3T3 Cells↗
PubMed1992

Characterization of an angiosarcoma-inducing mutation in the erbB oncogene.

The erbB oncogenes of two transducing viruses that arose in chicken 5005 have been molecularly characterized. One of these viruses, AEV-5005, caused erythroblastosis. The other, AAV-5005, caused angiosarcoma. Both viruses had identical 5' junctions of viral and host sequences, indicating that both arose from the same proviral insertion. The erbB oncogenes of both viruses encoded transmembrane, kinase and C-terminal domains of the chicken epidermal growth factor receptor. The C-terminal domain of the AEV-5005 erbB was complete, whereas that of AAV-5005 contained a 59 amino acid internal deletion (amino acids 993-1051 of the chicken epidermal growth factor receptor). Oncogenicity tests using retroviral constructs containing the erbB sequences from AEV-5005 and AAV-5005 demonstrated that both erbB genes caused erythroblastosis and that the 59 amino acid deletion conferred the ability to induce angiosarcoma. The 59 amino acid deletion also caused increased levels of erbB autophosphorylation in cells grown in the presence of sodium orthovanadate.

Amino Acid Sequence↗
PubMed1990

Alpha- and beta-adrenergic-receptor systems in bronchial asthma and in subjects without asthma: reduced mononuclear cell beta-receptors in bronchial asthma.

We assessed the adrenergic-receptor system in individuals with bronchial hyperreactivity, beta-Adrenergic receptors on mononuclear cell membranes, alpha-adrenergic receptors on platelet membranes, and the cAMP response in these cell types to different stimuli, including platelet-activating factor (PAF), were determined. Studies were assessed in 10 subjects with mild asthma, six methacholine-sensitive subjects without asthma, and 10 normal subjects. The density and affinity of beta-receptors and alpha-receptors were determined by Scatchard analysis. Our findings were that (1) subjects with asthma had a significantly lower density of beta-receptors compared to normal subjects, (2) subjects with asthma had a significantly lower cAMP response to isoproterenol stimulation compared to the two other groups, (3) in subjects without asthma. PAF decreased the basal cAMP level and significantly inhibited the response to isoproterenol stimulation, (4) there was no difference in density and affinity of platelet alpha-receptors or in platelet cAMP responses to stimulation by alpha-agonists among these three groups, and (5) neither cAMP response or beta-receptor density on mononuclear cells were significantly correlated with pulmonary-function tests (FEV/FVC times 100), sensitivity to methacholine, or cold-air inhalation. These results suggest that patients with asthma may have a lower isoproterenol cAMP response and decreased density of beta-adrenergic receptors on mononuclear cells in the absence of beta-agonist therapy. It is speculated that release of PAF and other mediators secondary to allergen exposure, even in the absence of overt attacks of asthma, may inhibit the response to endogenous or exogenous beta-adrenergic agonists.

Adolescent↗
PubMed1990

The therapeutic efficacy of oral cholecystographic agent (iopanoic acid) in the management of hyperthyroidism.

Five randomly chosen patients with thyrotoxicosis were administered 1 gm of the oral cholecystographic agent iopanoic acid daily for 21 days. There was a marked fall in T3 levels by 75% of the pretherapy value by 96 hr; values remained normal over the 21-day period. T4 values fell significantly by seven days of therapy, and the decreased values were sustained. FT3 and FT4I also showed corresponding decreases in value. All subjects showed clinical improvement by both subjective and objective criteria. During therapy, escape from the effect of iopanoic acid was not encountered. However, after stopping the drug for 2-4 wk, the patients' iodine-131 uptake become as high as the pretherapy level, enabling them to undergo radioiodine treatment for thyrotoxicosis. The treatment strategy can be aimed at achieving quick euthyroidism and in planning radioiodine treatment as early as possible in high risk patients. This treatment may also be useful in preoperative control of thyrotoxicosis.

Administration, Oral↗
PubMed1990

Follow up of alterations in thyroid hormones and thyrotropin in patients of Hodgkin's disease given mantle radiation.

Thirty five patients with Hodgkin's disease who had received mantle radiotherapy to the neck were investigated for thyroid dysfunction serially over many years post radiation. No incidence of clinical hypothyroidism was noted; however, biochemical hypothyroidism (raised TSH, normal T3 and T4) was seen at some time during follow up in 22 patients. Thirteen had high TSH values at the first post radiation examination: in 6 they remained high during follow up and in seven they fell to normal or near normal without thyroxine substitution at any time. TSH abnormalities were seen by 2-3 years post radiotherapy and the return to normal, when it occurred, was seen by 4-6 years. It is advisable to follow up patients with abnormal TSH values following mantle radiation for a further 2-3 years and begin thyroxine substitution only if TSH abnormalities persist.

Adolescent↗