PubMed Health⌕ Search

Biomedical subjects

T Masud

Publications and source records attributed to T Masud.

At least 37 records · Page 2Linked to original sources
PubMed1996

Glucocorticoids and acidosis stimulate protein and amino acid catabolism in vivo.

We have shown that chronic metabolic acidosis in awake rats accelerates whole body protein turnover using stochastic modeling and a continuous infusion of L-[1-13C] leucine. To delineate the role that glucocorticoids play in mediating these catabolic responses, we measured protein turnover in awake, chronically catheterized, adrenalectomized rats in the presence or absence of glucocorticoids and/or a NH4Cl feeding regimen which induced chronic metabolic acidosis. In adrenalectomized rats receiving no glucocorticoids there was no statistical difference in amino acid oxidation, protein degradation or synthesis whether or not the rats had acidosis. In contrast, chronically acidotic, adrenalectomized rats receiving glucocorticoids demonstrated accelerated whole body protein turnover with a 84% increase in amino acid oxidation and a 26% increase in protein degradation, compared to rats not receiving glucocorticoids or those given the same dose of glucocorticoids but without acidosis. We conclude that metabolic acidosis accelerates amino acid oxidation and protein degradation in vivo, and that glucocorticoids are necessary but not sufficient to mediate the catabolic effects of metabolic acidosis.

Acidosis↗
PubMed1996

Assessment of osteopenia from spine radiographs using two different methods: the Chingford Study.

Two methods for diagnosing radiological osteopenia in thoracic (TS) and lumbar (LS) spine radiographs were assessed: a subjective conventional method (A) and a semiquantitative method (B), by comparing them with bone mineral density (BMD) measured by dual energy X-ray absorptiometry (DEXA), in a population of "normal" women aged 45-70 years (n = 818). For both methods there was good intraobserver and interobserver reproducibility. BMDs were significantly lower with increasing radiological osteopenia grades (p < 0.001), and remained lower after adjustment for age and body mass index (p < 0.01). The proportion of subjects with DEXA-defined osteoporosis rose with increasing radiological osteopenia grades for both methods. The worst osteopenia categories identified 29.7-55.3% of women with DEXA-defined osteoporosis, compared with 6.1-11.7% in the "normal" categories. Both methods, however, showed a large degree of overlap of BMDs between the various radiological osteopenia grades. The sensitivity and specificity of method A in diagnosing osteoporosis were 45.3% and 78.4%, respectively, for the TS and 19.0% and 94.3%, respectively, for the LS. For method B the sensitivities and specificities were 8.8% and 96.1%, respectively (TS), and 10.2% and 95.6%, respectively (LS). Although both methods have poor sensitivities, "definite" or "high" grade osteopenia should be an indication for bone densitometry. The high specificities suggest that a "normal" (no osteopenia) X-ray is unlikely to have a significantly low BMD.

Absorptiometry, Photon↗
PubMed1996

How is lean body mass conserved with the very-low protein diet regimen?

Eight CRF patients (GFR = 18.8 +/- 2.7 ml/min) underwent a crossover comparison of a very-low-protein diet (VLPD) providing 0.28 g protein and 35 kcal/kg/day, plus an isomolar mixture of ketoacids (KA) or essential amino acids (EAA). During each dietary period, a 5-day nitrogen balance (BN) was performed and whole-body protein turnover (WBPT) was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Although the VLPD/KA regimen contained 15% less nitrogen, BN was neutral and did not differ between the regimens. Similarly, rates of WBPT did not differ between the KA or EAA regimens, and neutral BN was achieved by a marked suppression of amino acid oxidation and postprandial inhibition of protein degradation (PD). Participants were then discharged on the VLPD/KA regimen and monitored as outpatients for > or = 1 year. Repeat BN was neutral and rates of WBPT did not differ from baseline values. Thus, the adaptive responses to dietary protein restriction are sustained during long-term therapy.

Adult↗
PubMed1996

Generalized osteoarthritis in women: pattern of joint involvement and approaches to definition for epidemiological studies.

OBJECTIVE: To ascertain whether clustering between joint sites in osteoarthritis (OA) is more common than would be expected simply from the rising prevalence of the disorder with age, and to explore a definition of generalized OA (GOA) by determining the pattern of joint group involvement, in a population sample of peri and postmenopausal women. METHODS: Radiographs of the hands, knees, and hips were obtained in a population sample of 702 women aged 45 to 64 years. Distal interphalangeal, proximal interphalangeal, carpometacarpal, knee, and hip OA were assessed using the Kellgren-Lawrence grading system. Logistic regression was used to test for overall clustering of OA between joint sites, and log linear models were used to study the patterns of association between different sites. RESULTS: Multiple involvement of the 5 joint groups studied occurred significantly more frequently than could be expected by chance alone (chi 2 = 52.3, df = 5, p < 0.001), and this clustering remained significant after age adjustment (chi 2 = 26.1, df = 5, p < 0.001). Thresholds could be defined for the number of involved joint groups that distinguished a polyarticular subset of OA. These thresholds varied with age and the radiographic cutoff at which OA was assigned. Thus, for grade 2+ disease, GOA could be defined by involvement of 2 or more joint groups at age 45-47 years, but required involvement of all 5 joint groups at age 60-64 years. Symmetry within joint groups was the most pronounced feature in the pattern of joint involvement in the sample as a whole, with associations between different joint groups being substantially weaker than those for symmetrical bilateral involvement of a particular joint. CONCLUSION: There is a clear tendency towards polyarticular OA among women aged 45-64 years. However, there is no single threshold number of joint sites that can be used to define GOA. The pattern of joint involvement in OA is primarily symmetrical, and this pattern strongly suggests a systemic etiology in this subset of postmenopausal women.

Arthrography↗
PubMed1995

Long-term adaptive responses to dietary protein restriction in chronic renal failure.

Six patients with chronic renal failure (glomerular filtration rate 18 +/- 2 ml/min) underwent two 10-day admissions separated by at least 1 yr of outpatient therapy with a very low-protein diet (VLPD) providing 0.28 g protein.kg-1.day-1 plus an amino acid-ketoacid supplement. During each Clinical Research Center admission, subjects completed a 5-day nitrogen balance (BN), and whole body protein turnover was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Outpatient dietary protein compliance was very good (25 vs. 20 g protein/day or 125% goal), whereas energy intake was only 69% of goal (24 vs. 35 kcal.kg-1.day-1). During the 16 +/- 2 mo of dietary therapy, there were no changes in serum proteins or anthropometrics. BN after > or = 1 yr of dietary therapy was neutral and did not differ from initial values (+0.46 +/- 0.20 vs. +0.55 +/- 0.19 g N/day). Similarly, rates of whole body protein synthesis, degradation, and leucine oxidation after long-term therapy with the VLPD regimen did not differ from baseline values, and neutral BN was maintained by a marked suppression of amino acid oxidation and postprandial inhibition of protein degradation. This is the first evidence that the compensatory changes in whole body protein turnover activated in response to dietary protein restriction are sustained during long-term therapy.

Adaptation, Physiological↗
PubMed1995

A population study of the screening potential of assessment of trabecular pattern of the femoral neck (Singh index): the Chingford Study.

The trabecular pattern of the femoral neck (Singh index) has been used as a measure of osteopenia and fracture risk but the value of this method is controversial. This study assessed the usefulness of the Singh index (SI) by using dual energy X-ray absorptiometry (DXA) as the "gold standard". 659 Caucasian women (45-70 years) from an age-sex register of a general practice had their femoral neck and lumbar spine bone densities measured by DXA and had antero-posterior hip X-rays performed which were then categorized into six osteopenia grades using the SI method. The intraobserver and interobserver reproducibility of this method was good (kappa = 0.64 and 0.61, respectively). The SI grades correlated significantly with body mass index (r = 0.35) and age (r = 0.17) (p < 0.001). The mean femoral neck and lumbar spine bone densities were significantly higher with increasing SI grade even after adjustment for age and body mass index (p < 0.001). The proportion of subjects below the fracture threshold (2 SD below mean peak bone mass) decreased with increasing SI grade, ranging from 100% in SI grade 2 to 16.8% in SI grade 6. There was, however, wide overlap of bone densities between the grades. Using the criteria "osteoporosis < or = SI grade 4", the sensitivity and specificity of the SI method diagnosing low bone mass was 35.1% and 90.0%, respectively. These data suggest that the SI is a reproducible tool which may detect differences in bone mass between populations or subgroups within populations, although caution should be used in classifying individual patients because of the wide variation in bone density. The method has a low sensitivity but a relatively high specificity in diagnosing low bone mass.

Absorptiometry, Photon↗
PubMed1994

Adaptive responses to very low protein diets: the first comparison of ketoacids to essential amino acids.

Eight patients with chronic renal failure (GFR 18.8 +/- 2.7 ml/min) were randomized to a crossover comparison of a very low protein diet (VLPD) containing 0.28 g protein and 35 kcal per kg per day, plus an isosmolar mixture of either ketoacids (KA) or essential amino acids (EAA). Subjects initiated the diets 14 days before hospital admission and following a four-day equilibration, a five-day nitrogen balance (BN) was performed. Whole-body protein turnover (WBPT) was measured during fasting and feeding using intravenous [1-13C]leucine and intragastric [5,5,5-2H3]leucine. Even though the VLPD/KA regimen contained 15% less nitrogen, BN was neutral and did not differ between the regimens. Nitrogen conservation with KA was due to a reduction in urea nitrogen appearance. Rates of WBPT measured during fasting and feeding did not differ between the KA or EAA regimens. During both regimens, feeding decreased protein degradation, whereas protein synthesis was unchanged. Although feeding stimulated leucine oxidation, rates were 50 to 100% lower than reported in CRF patients consuming 0.6 or 1.0 g protein/kg/day. Thus, neutral Bn with the VLPD regimen is achieved by a marked reduction in amino acid oxidation and a postprandial inhibition of protein degradation.

Adaptation, Physiological↗
PubMed1994

The reliability of diagnosing osteoporosis from spinal radiographs.

In order to assess the value of spine radiographs in the diagnosis of osteoporosis, we have measured lumbar-spine bone mineral density (BMD) in 33 women aged 33-74 years whose radiographs were reported as showing 'osteopenia' only and 41 women aged 39-78 with radiological evidence of vertebral deformation. These results were compared with the normal range for young women and with control groups of 41 normal elderly women aged 65-70 and 15 normal younger women aged 50-60. Women with radiological osteopenia had a significantly lower BMD than the younger (p < 0.001) but not the older control group. The BMD in women with vertebral deformation was significantly lower than in both control groups (p < 0.001) and women with radiological osteopenia (p < 0.01). Only 67% of women with radiological osteopenia had a bone density below the normal range for young women, compared with 81% of those with vertebral deformation, though the latter may be an underestimate because of the artefactual elevation of bone mass caused by vertebral fractures in the lumbar spine. Our study suggests that a radiological report of reduced bone density may be misleading. Bone density measurements should be performed to confirm that patients so identified require treatment for osteoporosis. For patients with vertebral deformation after minimal or no trauma, bone density measurements are probably not required.

Absorptiometry, Photon↗
PubMed1994

Metabolic responses to nephrosis: effect of a low-protein diet.

To determine whether dietary protein restriction (LPD) causes protein catabolism in adriamycin nephrosis, nephrotic and control rats were paired by weight and gavage fed an 8.5% protein diet for 3 days (protocol 1) or 12 days (protocol 2). Fasting whole body protein turnover was then measured using a constant infusion of L-[1-14C]leucine. After 3 days of LPD, proteinuria decreased slightly and body weight did not change in either group. In contrast, leucine oxidation and urinary urea nitrogen excretion in nephrotic rats decreased by 18% and 37%, respectively (P < or = 0.05). After 12 days of LPD, weight loss did not differ between groups. In contrast to protocol 1, proteinuria decreased by 45% in nephrotic rats fed LPD for 12 days, and leucine oxidation rats increased to the level of control rats. Rates of whole body protein synthesis (PS) and degradation (PD) did not differ between nephrotic and control rats receiving LPD for 3 or 12 days, but were significantly lower than rates measured in rats fed 22% protein. We conclude that 1) proteinuria stimulates protein conservation even when dietary protein intake is restricted; 2) the decrease in amino acid oxidation was dependent on moderate proteinuria, since prolonged LPD ameliorated nephrosis and leucine oxidation rates increased to control levels; and 3) since weight loss and rates of whole body PS and PD in nephrotic and control animals were indistinguishable, moderate proteinuria did not increase protein catabolism.

Animals↗
PubMed1994

A randomized trial of two etoposide schedules in small-cell lung cancer: the influence of pharmacokinetics on efficacy and toxicity.

PURPOSE: Etoposide is a schedule-dependent drug, as demonstrated by the superiority of 5 consecutive daily infusions over a continuous 24-hour infusion in patients with small-cell lung cancer. A randomized trial has therefore been conducted to compare an extended 8-day regimen with the 5-day schedule. PATIENTS AND METHODS: Ninety-four patients with small-cell lung cancer (35 limited disease, 59 extensive disease) were randomized to receive single-agent etoposide 500 mg/m2, either as 5 daily 2-hour infusions of 100 mg/m2 or as 8 daily 75-minute infusions of 62.5 mg/m2, both repeated every 3 weeks for six cycles. Single-agent carboplatin was administered at relapse in both arms of the study. Patients were stratified at randomization according to extent of disease and Karnofsky performance status (KPS). RESULTS: The overall response rate was 81% in the 5-day arm and 87% in the 8-day arm, with median survival durations of 7.1 and 9.4 months, respectively (no significant differences). The time over which plasma etoposide exceeded low plasma concentrations was significantly longer in patients who responded compared with patients who did not respond. This was most significant for time at concentrations greater than 1, 1.5, and 2 micrograms/mL. Hematologic toxicity was significantly worse in the 5-day arm of the study (cycle no. 1 nadir neutrophil count, 0.8 x 10(9)/L v 1.7 x 10(9)/L). Stepwise regression analysis found duration of exposure to plasma etoposide greater than 3 micrograms/mL to be predictive of nadir neutrophil count and duration of exposure to plasma etoposide greater than 2 micrograms/mL to be predictive of nadir WBC count. CONCLUSION: The 5-day and 8-day regimens had equivalent activity in small-cell lung cancer. A pharmacokinetic association between concentrations of etoposide and response and toxicity was found. Antitumor activity was associated with the maintenance of lower levels of etoposide than found to be associated with hematologic toxicity. This supports the hypothesis that the schedule of etoposide administration may affect efficacy and toxicity, and that prolonged exposure to low concentrations of etoposide may improve the therapeutic ratio for this drug.

Adult↗
PubMed1993

Mechanisms of adaptation to proteinuria in adriamycin nephrosis.

To evaluate the impact of urinary protein losses on whole body protein turnover (WBPT) independent of acidosis or uremia, we utilized a model of unilateral adriamycin nephrosis. Control rats were matched by weight to nephrotic rats and pair fed 22% protein chow for 14-18 days; urinary urea nitrogen (UUN) was measured on day 12, and leucine turnover measurement was performed on the final day. Growth rates of nephrotic and pair-fed control rats did not differ during the first 2 wk of pair feeding; thereafter, a small difference in growth could be detected. Despite an identical intake of dietary protein, UUN excretion was 29% less in the nephrotic rats (P < or = 0.02). Fasting whole body protein synthesis and degradation did not differ between nephrotic and control rats; in contrast, leucine oxidation decreased by 21% in nephrosis (P < 0.05). On the basis of near normal growth and normal rates of WBPT, we conclude that nephrotic rats fed ad libitum can adapt to the stress of continuous protein losses. A reduction in amino acid oxidation and UUN excretion were the primary mechanisms responsible for protein conservation in experimental nephrosis.

Animals↗
PubMed1992

Chronic metabolic acidosis accelerates whole body proteolysis and oxidation in awake rats.

Previous work has documented an acceleration of proteolysis and branched-chain amino acid oxidation when muscles from rats with chronic metabolic acidosis were incubated in vitro. The present study examines the impact of chronic metabolic acidosis on whole body amino acid turnover and oxidation in chronically catheterized awake male Sprague-Dawley rats using stochastic modeling and a primed continuous infusion of L-[1-14C] leucine. Whole body protein turnover was accelerated by acidosis as reflected in a 70% increase in proteolysis and a 55% increase in protein synthesis. Amino acid oxidation was increased 145% in rats with chronic metabolic acidosis relative to control rats receiving diets identical in protein and calories based on a reciprocal pool model and plasma alpha-ketoisocaproate specific radioactivity. These changes were accompanied by a 104% increase in liver branched-chain ketoacid dehydrogenase (BCKAD) activity in rats with acidosis, similar to previously documented increases in skeletal muscle BCKAD activity caused by acidosis. In contrast, kidney BCKAD activity was decreased 38% by acidosis, illustrating the tissue-specificity of the changes that were present. We conclude that chronic metabolic acidosis accelerates whole body protein turnover and affects the reincorporation of amino acid into body proteins by accelerating amino acid oxidation.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1992

Lipid and lipoprotein metabolism in familial combined hyperlipidaemia during treatment of sporadic phaeochromocytoma: a case study.

Lipid metabolism was evaluated during management of phaeochromocytoma in a 41 year old non-obese post-menopausal women with familial combined hyperlipidaemia. The main effect of the excess catecholamine secretion on lipid metabolism was increased lipolytic activity, lower serum triglyceride and increased HDL cholesterol concentrations, compared with findings following removal of the tumour. Before removal of the tumour, the use of beta blockers alone led to marked deterioration of the hyperlipidaemic state, and combined alpha and beta blockade additionally led to a marked reduction in fat oxidation and lipoprotein lipase activity. Overactivity of the adrenergic system leads to changes in lipid metabolism in phaeochromocytoma. Treatment of the phaeochromocytoma may lead to worsening of hyperlipidaemia pre-existing in such individuals.

Adrenal Gland Neoplasms↗
PubMed1992

Metabolic acidosis accelerates whole body protein degradation and leucine oxidation by a glucocorticoid-dependent mechanism.

Previous work documented an acceleration of proteolysis and branched-chain amino acid oxidation when muscles from rats with chronic metabolic acidosis were incubated in vitro. The present study examines the impact of chronic metabolic acidosis on whole body amino acid turnover and oxidation in chronically catheterized, awake, male Sprague-Dawley rats using stochastic modeling and a primed continuous infusion of L[1-14C] leucine. Whole body protein turnover was accelerated by acidosis as reflected in a 70% increase in proteolysis and a 55% increase in protein synthesis. Amino acid oxidation was increased by 145% in rats with acidosis relative to control rats receiving diets identical in protein and calories based on a reciprocal pool model and plasma alpha-ketoisocaproate specific radioactivity. These changes were accompanied by a 104% increase in liver branched-chain ketoacid dehydrogenase (BCKAD) activity in rats with acidosis, similar to previously documented increases in skeletal muscle BCKAD activity caused by acidosis. In contrast, kidney BCKAD activity was decreased by 38%, illustrating the tissue specificity of the changes that were present. We conclude that chronic metabolic acidosis accelerates whole body protein turnover and reduces the efficiency of protein utilization by accelerating amino acid oxidation. These changes may require an intact glucocorticoid axis.

Acidosis↗