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Biomedical subjects

B Rajagopalan

Publications and source records attributed to B Rajagopalan.

At least 91 records · Page 5Linked to original sources
PubMed1990

Study of human liver disease with P-31 magnetic resonance spectroscopy.

Liver metabolism and energetics of 24 patients with liver disease were studied using phosphorus-31 magnetic resonance spectroscopy. Significant abnormalities were detected in the majority of these patients. A striking diversity in metabolic patterns was observed. Patients with acute viral hepatitis had low liver phosphodiesters and high phosphomonoesters, possibly phosphocholine and phosphoethanolamine. In alcoholic hepatitis phosphomonoesters were raised. Intracellular inorganic phosphate and inorganic phosphate/ATP ratios were decreased in primary biliary cirrhosis and in some patients with hepatitis. These spectroscopic results were evaluated in respect of the pattern of liver damage and cellular regeneration. Liver tumours had raised phosphomonoesters and also showed evidence for altered spin-lattice relaxation of the phosphorus nucleus in various metabolites. In iron overload the liver ATP resonances were broadened. The line broadening correlated with the degree of iron overload suggesting the potential use of P-31 magnetic resonance spectroscopy for measuring liver iron.

Adult↗
PubMed1990

Nonpalpable breast masses: radiologic predictability of malignancy.

Of 568 nonpalpable breast lesions detected by screening mammography 242 proved to be noncalcified masses; biopsy showed 165 to be benign and 77 malignant. The lesions were evaluated with respect to contour, radiographic density and size. Of the malignant lesions 90% were infiltrating carcinomas, 88% of which had an indistinct contour and were of moderate to high density. Of the benign lesions 40% of those with an indistinct contour demonstrated high radiographic density. Low-density, distinct masses were all benign. There was no correlation between the size of the lesion and whether it was malignant.

Aged↗
PubMed1989

Phospholipid bilayer contribution to 31P NMR spectra in vivo.

The magnetic field-dependent phosphodiester (PDE) signal found in 31P NMR spectra of liver and brain has been studied using saturation transfer and proton decoupling techniques. This PDE component, which accounts for as much as 45% of the signal in vivo, has been identified as primarily phospholipid bilayer with a small contribution from a motionally averaged macromolecule(s).

Animals↗
PubMed1989

Human primary brain tumour metabolism in vivo: a phosphorus magnetic resonance spectroscopy study.

Magnetic resonance spectroscopy was used to study intracellular pH and compounds which contain phosphorus in normal human brain and primary brain tumours non-invasively. In normal subjects (n = 7) intracellular pH (pHi) of the brain was 7.03 +/- 0.02 (mean +/- s.e.m.). The pHi did not vary between superficial (2 cm, majority grey matter) and deep brain (5 cm, majority white matter). The relative concentrations of phosphocreatine (PCr) and phosphomonoesters (PME) to ATP were also constant with depth. The relative concentration of phosphodiesters (PDE) increased from superficial to deep in normal brain. The astrocytomas (n = 7, grade II-IV) were significantly more alkaline (pHi = 7.08 +/- 0.03), and contained more PCr and PME, with respect to ATP, than normal brain at similar depth. The meningiomas (n = 4) were also more alkaline (pHi = 7.19 +/- 0.02) with a raised PME level but reduced PCr. The reduction in meningioma PCr may be due to the significant necrosis (greater than 20%) seen in the surgical biopsies. No significant necrosis was seen in the gliomas. Previous in vitro studies suggest that increased PME may be due to accumulation of phosphoethanolamine (PE), a phospholipid precursor. These results suggest that human primary brain tumours characteristically are more alkaline with increased PME than normal brain.

Adult↗
PubMed1989

Measurement of transmural distribution of phosphorus metabolites in the pig heart by 31P magnetic resonance spectroscopy.

We used the phase modulated rotating frame imaging technique to measure transmural distribution of phosphorus metabolites in 10 anaesthetised ventilated pigs using a double surface coil placed on the surface of the left ventricle. Anaesthesia was maintained in five animals with halothane, barbiturate and nitrous oxide and in five others with intravenous chloralose. 31Phosphorus spectra were acquired, gated to expiration and systole. From phantom experiments the resolution of the experiment was shown to be approximately 2 mm. The anatomical limits of the myocardium were identified by the appearance of 2,3-diphosphoglycerate peaks from red blood cells. The limits of the epicardium were confirmed by obtaining images after placing a phantom containing fluorophosphate on the surface of the heart. The endocardium was identified by inserting a small balloon catheter through the centre of the coil into the left ventricular cavity, filling it with 0.5 ml of fluorophosphate and pulling it gently against the endocardium. No transmural differences in phosphocreatine to ATP ratio were identified in the normal heart. The animals anaesthetised with chloralose showed a significantly higher phosphocreatine to ATP ratio compared to those anaesthetised with halothane and barbiturate. The chloralose animals tended to have a higher blood pressure and a lower heart rate when compared to the other animals. No transmural differences, however, were identified in either group. When regional ischaemia was produced using a snare to occlude the left coronary artery, phosphocreatine fell and the signal from the inorganic phosphate + 2,3-diphosphoglycerate region increased. The inner wall tended to become more acid compared to the outer wall during ischaemia. These experiments show that the phase modulated rotating frame imaging technique can be used to study the effects of changes in workload, ischaemia, or pharmacological intervention on transmural distribution of metabolites in the heart and thus help elucidate factors responsible for subendocardial vulnerability to stress.

2,3-Diphosphoglycerate↗
PubMed1989

Chronically obstructed sinonasal secretions: observations on T1 and T2 shortening.

Clinically assessed chronic proteinacious sinonasal secretions usually have long T1 and T2 relaxation times reflecting their high water content. However, in some cases variable combinations of short and long T1 and T2 relaxation times are found. To study the causes of these findings, the magnetic resonance (MR) images of 41 patients with surgically proved, chronically obstructed sinonasal secretions were studied. The relative signal intensities on both T1- and T2-weighted sequences of the sinus specimens were correlated with the gross viscosity of the specimens at surgery. Ten specimens were collected that were not contaminated with either blood or saline. UV spectrophotometric analysis of four of these samples excluded the presence of methemoglobin. Total protein content was determined in five samples, and in vitro T1 and T2 values were measured in one sample. These T1 and T2 relaxation times were accurately predicted with use of a standard pure lysozyme protein solution with the same concentration as the specimen. In addition, the observed T1- and T2-weighted signal intensities on the 41 MR images were predicted from an analysis of pure protein solutions. This study concludes that the primary causes of the variable T1 and T2 relaxation times of chronic sinonasal secretions are the macromolecular protein concentration, the amount of free water, and the specimen viscosity. Furthermore, an orderly and predictable transition of these signal intensities occurs over time.

Chronic Disease↗
PubMed1989

The effects of anti-hypertensive drugs on sexual function in men and women: a report from the DHSS Hypertension Care Computing Project (DHCCP).

One thousand, two hundred and eighty-five men and 1,080 women being followed in the DHSS Hypertension Care Computing Project answered the questions on sexual activity included in a self-administered questionnaire. In men, both impotence and sexual inactivity were increased in patients receiving hydralazine. No gross excess of these complaints could be determined in patients receiving either beta-adrenoceptor blocking drugs or methyldopa, nor was failure of ejaculation increased with these drugs. The survey could not exclude any deterioration in sexual function occurring uniformly across all treatment groups. However, the rates of complaint were similar in men taking a diuretic alone, a beta-adrenoceptor blocking drug alone and those taking the combination of these two drug groups. In women with hypertension, frequency of sexual intercourse and the achievement of orgasm was not associated with the giving of hydralazine, beta-adrenoceptor blocking drugs or methyldopa.

Adult↗
PubMed1988

Alterations of skeletal muscle metabolism in humans studied by phosphorus 31 magnetic resonance spectroscopy in congestive heart failure.

Muscle metabolism of the finger flexor muscle of the dominant arm was examined in patients with congestive heart failure and age-related controls. Phosphocreatine utilization and decrease in pH during exercise was significantly greater in patients than in controls. Recovery rates were slow in some of these patients. Measurements of forearm blood flow at rest or during exercise were not significantly reduced in patients compared with controls. The inorganic phosphate peak was split during exercise in some of the patients, suggesting the presence of more glycolytic fibers in their muscles. These observations suggest that metabolic abnormalities may be present in the skeletal muscles of patients with heart failure that are not due to reduced nutritive blood flow. This may, in part, explain the lack of correlation between measurements of cardiac function and exercise tolerance in these patients.

Adenosine Triphosphate↗
PubMed1988

31P NMR measurements of myocardial pH in vivo.

A 31P NMR magnetization transfer method for measuring myocardial pH in vivo is demonstrated in the lamb, dog and cat. The method involves measuring the difference in chemical shift between the resonances of phosphocreatine and inorganic phosphate in magnetization transfer difference spectra in which the gamma-phosphate resonance of ATP has been saturated. The method has been verified by measuring the chemical shift difference between the resonances of 2-deoxyglucose 6-phosphate and phosphocreatine following infusion of the animals with 2-deoxyglucose. The measured pH values are significantly lower than those obtained in previous studies on the heart in vivo.

Animals↗
PubMed1988

Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure. Evidence for abnormalities unrelated to blood flow.

Previous studies with 31P nuclear magnetic resonance have demonstrated that patients with chronic congestive heart failure often exhibit increased glycolytic metabolism and impaired oxidative phosphorylation in exercising skeletal muscle, but the mechanism for these changes remains unresolved. This study was conducted to determine whether these abnormalities result from impaired blood flow or oxygen delivery. Nine patients with mild-to-moderate congestive heart failure and nine age- and size-matched, healthy control volunteers were studied during repetitive submaximal finger flexion exercise under aerobic and ischemic conditions. Skeletal muscle metabolism was assessed by 31P nuclear magnetic resonance of the flexor digitorum superficialis muscle. During steady-state aerobic exercise at 33% of each subject's predetermined maximum workload, the patients with congestive heart failure exhibited significantly lower pH values (6.65 +/- 0.22 vs. 6.97 +/- 0.09, p less than 0.002) and phosphocreatine concentrations, expressed as [phosphocreatine]/([phosphocreatine] + [inorganic phosphate]) (0.59 +/- 0.14 vs. 0.79 +/- 0.08, p less than 0.002). Similar differences were also present throughout ischemic exercise at the same workload. Based upon these measurements, calculated lactate production and adenosine 5'-triphosphate consumption rates were significantly higher in the patients with congestive heart failure. These results indicate that in many patients with congestive heart failure exercising muscle exhibits increased glycolytic metabolism and appears to be metabolically less efficient in relation to external work performed. These changes cannot be explained by impaired blood flow or oxygen delivery alone.

Adult↗
PubMed1988

Metabolic changes during experimental cerebral ischemia in hyperglycemic rats, observed by 31P and 1H magnetic resonance spectroscopy.

Progressive cerebral ischemia was induced in seven anesthetized hyperglycemic rats by carotid artery ligation and hemorrhagic hypotension. Phosphorus metabolites, intracellular pH, and lactate in the brain were monitored by 31P and 1H magnetic resonance spectroscopy. Under conditions in which blood flow was low, phosphocreatine (PCr) concentration and intracellular pH decreased and the concentration of lactate increased. The decrease in ATP was approximately one-third that of PCr until only 25% PCr remained, after which ATP was lost more rapidly than PCr. These changes were interpreted in terms of three regions observed by the magnetic resonance coil, one of complete ischemia, one of partial ischemia, and one of perfusion sufficient to maintain normal metabolite levels. The extent of the three regions was estimated quantitatively. Broadening and splitting of the inorganic phosphorus (Pi) peak into two components provided further evidence of distinct populations of cells, one very acidic and another less so. Apparent intracellular buffering capacity was calculated as 23.6 +/- 1.3 mumol lactate/g wet wt/pH.

Acidosis, Lactic↗
PubMed1988

Study of liver metabolism in glucose-6-phosphatase deficiency (glycogen storage disease type 1A) by P-31 magnetic resonance spectroscopy.

Liver metabolism of two patients (aged 15 and 23 yr) was studied by P-31 magnetic resonance spectroscopy at 1.9 tesla. The P-31 spectra of liver showed the resonances of phosphomonoesters (including sugar phosphates), inorganic phosphate (Pi), phosphodiesters (e.g. glycerophosphorylcholine, glycerophosporylethanolamine), and ATP. These resonances were quantified by expressing their peak areas in mM (assuming that ATP concentrations in normal liver is 2.5 mM) or as a ratio relative to the area of the phosphodiester resonance. After an overnight fast liver phosphomonoesters in patients were 2.6 and 1.6 AU, respectively (controls 1.1 +/- 0.5, mean +/- 2 SD, n = 17). At the same time liver Pi was decreased in patients to 1.3 and 1.0, respectively (controls 1.8 +/- 0.8). Based on chemical shift measurements the increase in phosphomonoesters could be attributed to accumulation of sugar phosphates (mainly glycolytic intermediates). After 1 g/kg oral glucose, hepatic sugar phosphates decreased in patients by 64 and 40%, respectively, and reached normal levels (on the absolute intensity scale); whereas liver Pi increased by 130 and 40%, respectively. Liver Pi levels remained elevated in both patients 30 min after ingestion of glucose. Liver sugar phosphates and Pi did not change in control subjects (n = 4) after glucose. In contrast to some previous reports, we have found accumulation of glycolytic intermediates in the liver of glucose-6-phosphatase-deficient patients during fasting. In these patients high levels may enhance the activity of residual glucose-6-phosphatase thus increasing hepatic glucose production and reducing the degree of hypoglycemia during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Study of hereditary fructose intolerance by use of 31P magnetic resonance spectroscopy.

The effect of fructose on liver metabolism in patients with hereditary fructose intolerance (HFI) and in heterozygotes for HFI was studied by 31P magnetic resonance spectroscopy (31P-MRS). In patients with HFI (n = 5) ingestion of small amounts of fructose was followed by an increase in sugar phosphates and decrease in inorganic phosphate (Pi) in the liver that could be detected by 31P-MRS. 31P-MRS could be used to diagnose fructose intolerance and to monitor the patients' compliance with a fructose-restricted diet. In heterozygotes (n = 8) 50 g fructose given orally led to accumulation of sugar phosphates and depletion of Pi in the liver. Fructose also induced a larger increase in plasma urate in heterozygotes than in control subjects. The effect of fructose on liver Pi and plasma urate was most pronounced in heterozygotes with gout (n = 3). Heterozygosity for HFI may predispose to hyperuricaemia.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1987

31P nuclear magnetic resonance evidence of abnormal skeletal muscle metabolism in patients with congestive heart failure.

In patients with congestive heart failure (CHF), exercise limitation correlates poorly with central hemodynamic abnormalities, suggesting that additional abnormalities in skeletal muscle blood flow or metabolism play an important pathophysiologic role. Therefore, muscle metabolism was examined by 31P nuclear magnetic resonance (NMR) at rest and during repetitive bulb squeeze exercise in 11 patients with New York Heart Association class II to IV CHF and 7 age-matched control subjects. Serial spectra were obtained at rest, at 2 levels of exercise and during recovery. At rest, the only abnormal finding was an elevated inorganic phosphate (Pi) concentration (5.0 +/- 1.5 vs 3.6 +/- 0.4 mM, p less than 0.01). At the lower exercise level, phosphocreatine (PCr) utilization, which was followed as the ratio of [PCr]/[( PCr] + [Pi]), was greater (0.36 +/- 0.16 vs 0.53 +/- 0.10, p less than 0.02), and pH fell more rapidly and to a lower value (6.38 +/- 0.25 vs 6.85 +/- 0.17, p less than 0.001). At the higher level of exercise, the patients could not work effectively and the group differences narrowed. Compared with control subjects, acidification was disproportionately greater in relation to PCr depletion in patients, further suggesting excessive dependence on glycolytic metabolism. The Pi peak was prominently double in 5 patients, indicating presence of a population of muscle fibers undergoing unusually active glycolysis. PCr resynthesis, a reflection of oxidative phosphorylation, was delayed in 4 patients. These findings indicate that in many patients with CHF, exercising muscle has marked metabolic changes consistent with impaired substrate availability and altered biochemistry.

Adenosine Triphosphate↗
PubMed1987

Quantitative studies of human cardiac metabolism by 31P rotating-frame NMR.

We have developed 31P NMR spectroscopic methods to determine quantitatively relative levels of phosphorous-containing metabolites in the human myocardium. We have used localization techniques based on the rotating-frame imaging experiment and carried out with a double-surface coil probe. Information is obtained from selected slices by rotating-frame depth selection and from a complete one-dimensional spectroscopic image using phase-modulated rotating-frame imaging. The methods collect biochemical information from metabolites in human heart, and we use the fact that the phosphocreatine/ATP molar ratio in skeletal muscle at rest is higher than that in working heart to demonstrate that localization has been achieved for each investigation. The phosphocreatine/ATP molar ratio in normal human heart has been measured as 1.55 +/- 0.20 (mean +/- SD) (3.5-sec interpulse delay) in six subjects using depth selection and as 1.53 +/- 0.25 (mean +/- SD) in four subjects using spectroscopic imaging. Measurement of this ratio is expected to give a useful and reproducible index of myocardial energetics in normal and pathological states.

Adenosine Triphosphate↗