Observation of coherent millimeter and submillimeter emission from a microtron-driven Cherenkov free-electron laser.
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Journal Article↗
Biomedical subjects
A Doria
Publications and source records attributed to A Doria.
Myocardial metabolism in type 1 diabetic patients without coronary artery disease.
Myocardial exchange of metabolic substrates was investigated in eight Type 1 diabetic patients with angiographically normal coronary arteries and seven normal control subjects, after an overnight fast. Simultaneous samples of arterial and coronary sinus blood were collected for analysis of the major metabolic substrates. Myocardial blood flow was measured by the thermodilution technique. Although the Type 1 patients were hyperglycaemic (10.0 +/- 2.0 (+/- SE) mmol I-1) myocardial glucose uptake was lower than in control subjects (27 +/- 6 vs 42 +/- 5 mumol min-1 1.73 m-2, p less than 0.05). The net balance of lactate and pyruvate across the myocardium showed a net release in Type 1 patients (13.4 +/- 2.7 mumol min-1 1.73 m-2 and 1.3 +/- 0.2 mumol min-1 1.73 m-2, respectively) and a net uptake in control subjects (2.2 +/- 0.7 mumol min-1 1.73 m-2 and 3.5 +/- 0.3 mumol min-1 1.73 m-2, both p less than 0.01). Myocardial uptake of ketone bodies was significantly higher in diabetic patients (37.0 +/- 6.3) mumol min-1 1.73 m-2) than in control subjects (10.1 +/- 3.4 mumol min-1 1.73 m-2, p less than 0.01). Non-esterified fatty acid (NEFA) uptake was significantly greater in the diabetic patients than in control subjects (44.1 +/- 7.0) vs 24.1 +/- 5.1 mumol min-1 1.73 m-2, p less than 0.01). Net balance of glucose, lactate, and pyruvate across the myocardium was inversely and significantly related to that of NEFAs and ketone bodies (p less than 0.01). Myocardial carbohydrate uptake is markedly impaired in Type 1 diabetic patients with angiographically intact coronary vessels. Ketones and NEFA represent the major fuel for the diabetic myocardium. Thus, in diabetes, myocardial lactate metabolism may be profoundly altered independently of coronary artery disease.
Blood Glucose↗
Insulin resistance is associated with high sodium-lithium countertransport in essential hypertension.
The nature of the association between essential hypertension and insulin resistance remains unknown. We measured plasma glucose and insulin levels after an oral glucose tolerance test (OGTT), as well as insulin sensitivity (using a euglycemic hyperinsulinemic clamp), glucose turnover (Rd; using [6,6-2H2]- and [3-3H]glucose isotopic dilution), and forearm net balance of glucose (using arterial-venous difference) in 22 hypertensive patients with high (H2) red blood cell (RBC) sodium-lithium countertransport (Na(+)-Li+ CT; greater than 0.41 mmol.l RBC-1.h-1), 21 hypertensive patients with normal (H1) Na(+)-Li+ CT, and 22 normotensive controls (C). After OGTT, H2 patients had higher plasma glucose and insulin levels than H1 and C. During euglycemic hyperinsulinemia (approximately 100 microU/ml) Rd was lower in H2 [21.7 +/- 1.4 (SE) mumol.kg-1.min-1] than in H1 (44.3 +/- 2.9; P less than 0.01) and C (48.1 +/- 3.0; P less than 0.01), and an inverse correlation was found between rates of Na(+)-Li+ CT and Rd in H1 and H2 (rs = -0.76; P less than 0.01). Forearm glucose uptake was 40-50% lower in H2 compared with H1 and C (P less than 0.01). Lactate concentration increased more in C (from 511 +/- 24 to 1,207 +/- 69 microM) and in H1 (from 564 +/- 40 to 1,122 +/- 99) than in H2 (from 581 +/- 42 to 950 +/- 102, P less than 0.05 vs. both). Forearm blood flow increased more in C (31%, P less than 0.05) and H1 (22%, P less than 0.05) than in H2 (12%).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Esophageal involvement in mixed connective tissue disease.
A study of esophageal symptoms and function was performed in 21 patients with mixed connective tissue disease (MCTD). Esophageal involvement was found in 18 cases (85%), in 14 (66%) with typical symptoms, in 15 (71%) with manometric abnormalities and in 11 (57%) with both. The manometric pattern was characterized by reduction of amplitude and coordination of peristaltic waves throughout the esophageal body and reduction of lower esophageal sphincter (LES) competency. In comparison, 38 patients with systemic sclerosis showed a similar but more severe pattern, particularly at the level of the distal esophagus and LES. Thus, although similar, the esophageal involvement in MCTD was not exactly the same as that of systemic sclerosis. Furthermore, in MCTD a correlation between manometric abnormalities and cutaneous involvement was lacking, and this suggests that esophageal disorders are not always linked with clinically evident scleroderma-like features of this disease. Since the diagnosis of MCTD is made in the presence of the clinical picture of more than one connective tissue disease, the detection of esophageal involvement by a sensitive technique such as esophageal manometry in a patient with suspected MCTD may be a useful diagnostic aid.
Adult↗
Recurrent dislocation of the elbow.
Twelve cases of recurrent dislocation of the elbow have been studied with special reference to the cause of instability, the operative findings and the results of treatment. We consider the major cause to be insufficiency of the posterolateral capsule and ligaments, and therefore the best treatment is a posterolateral capsulorraphy.
Adolescent↗
Anti-double-stranded DNA antibodies in the healthy elderly: prevalence and characteristics.
Using Crithidia luciliae fluorescent assay a significant prevalence (7.6%; P less than 0.006) of anti-double-stranded DNA antibodies was found in a healthy old population. A negative enzyme-linked immunosorbent assay for anti-total histone antibodies excluded a false-positive reaction. Anti-double-stranded DNA antibodies in the aged differed from those found in patients with systemic lupus erythematosus and were characterized by a low titer (95.6% of cases), belonging to the IgA class alone (95.6%), no complement-fixing ability (100%), and negativity to Farr assay (100%). It is concluded that, in elderly subjects without signs and symptoms of disease, including systemic lupus erythematosus, such a peculiar anti-double-stranded DNA antibody may be detected.
Adult↗
Substrate availability other than glucose in the brain during euglycemia and insulin-induced hypoglycemia in dogs.
Alternative substrates other than glucose could be used by the brain. In this study we hypothesized that lactate and ketone bodies can provide a significant portion of oxidative brain substrates in insulin-dependent diabetes mellitus (IDDM). Six control (C) and six insulin-treated streptozotocin diabetic (IDDM) dogs were studied during euglycemia (EU) and acute insulin induced hypoglycemia (HYPO). During EU for similar plasma glucose concentration (5.5 +/- 0.4 v 5.2 +/- 0.2 mmol/L in IDDM dogs showed a higher baseline lactate concentration (1.5 +/- 0.25 v 0.74 +/- 0.10 mmol/L; P less than .05). The ketone body concentrations were also increased in IDDM dogs but this increase was not statistically significant. The brain glucose uptake was 6.9 +/- 0.6 mumol/kg/min in C and 5.4 +/- 0.7 in IDDM. Lactate was released by the brain both in IDDM dogs (11.36 +/- 1.8 mumol/kg/min) and in C dogs (3.87 +/- 0.9; P less than .05). The brain ketones rate of disappearance (Rd) was 0.3 +/- 0.05 mumol/kg/min in IDDM dogs and 0.19 +/- 0.08 in C dogs. During HYPO the glucose uptake across the brain was 2.88 +/- 0.7 mumol/kg/min in IDDM and 3.12 +/- 0.5 in C dogs. We observed an overall brain lactate release (3.21 +/- 1.7 mol/kg/min) in C dogs and a net uptake (13.44 +/- 1.1; P less than .01) in IDDM (P less than .01). The brain ketones Rd was 0.1 +/- 0.2 mumol/kg/min in IDDM and 0.1 +/- 0.1 in C dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxybutyric Acid↗
Myocardial metabolism in insulin-deficient diabetic humans without coronary artery disease.
Eleven insulin-dependent diabetes mellitus (IDDM) patients with angiographically normal coronary arteries and a normal hemodynamic response to an echocardiographic-dipyridamole test and 12 normal controls were studied at rest and after atrial pacing simultaneously sampling arterial and coronary sinus blood. In IDDM patients, despite hyperglycemia [10.0 +/- 2.0 (SE) mmol/l], myocardial glucose uptake was slightly lower than in controls. This process was significantly activated in both groups during atrial pacing. The isotopically calculated net flux of lactate across myocardium, in agreement with the net balance value based on unlabeled lactate-pyruvate arteriovenous differences, showed a net uptake in controls (3.5 +/- 0.6 mumol.min-1.1.73 m-2) and a net release in IDDM (12.4 +/- 2.6; P less than 0.01). Atrial pacing stimulated lactate uptake in both groups. Myocardial uptake of ketone bodies was significantly higher in IDDM (37.0 +/- 6.3 mumol.min-1.1.73 m-2) than in controls (10.1 +/- 3.4 mumol.min-1.1.73 m-2; P less than 0.01). Free fatty acid uptake was also significantly greater in IDDM than in controls (44.1 +/- 7.0 vs. 24.1 +/- 5.1 mumol.min-1.1.73 m-2; P less than 0.01). Alanine and branched amino acids were released by diabetic but not by control hearts at rest. The normalization of blood glucose concentrations restored normal patterns of lactate and ketone body kinetics across diabetic myocardium. In conclusion, 1) at rest, myocardial lactate and amino acid uptake is markedly impaired in IDDM without coronary artery disease, and 2) the metabolic abnormalities of the diabetic myocardium are not a primary phenomenon but rather a consequence of hypoinsulinemia and hyperglycemia because insulin administration, resulting in euglycemia, restored normal patterns of cardiac metabolism.
Adult↗
Impaired renal response to a meat meal in insulin-dependent diabetes: role of glucagon and prostaglandins.
The renal response to 100 g/1.73 m2 protein load in the form of a meat meal was studied in 19 normal subjects and 35 normoalbuminuric insulin-dependent diabetic patients (IDDs) under conditions of sustained euglycemia. The area under the glomerular filtration rate (GFR) curve rose above base line by 1,904 +/- 292 in normals and 502 +/- 237 ml/1.73 m2 in IDDs (P less than 0.01). The meat meal induced a greater increment in the area under the glucagon curve in normals (14,930 +/- 186 pg.ml-1.min-1) than in IDDs (7,227 +/- 67, P less than 0.01); similarly urinary excretion of prostaglandin E2 and 6-ketoprostaglandin F1 alpha rose by 119 and 98%, respectively, in normals but only by 2% (P less than 0.01 vs. normals) and 10% (P less than 0.01 vs. normals) in IDDs. The fractional albumin clearance rose by 102 and 251% in normals and IDDs, respectively. In five normal subjects indomethacin administration abolished the GFR, glucagon, prostaglandin, and albuminuric response to meat ingestion. Glucagon replacement under indomethacin treatment failed to restore these responses. In five diabetic patients, selected for having a flat glucagon and GFR response to a meat meal, replacement of glucagon to postprandial levels increased urinary vasodilatory prostaglandins and restored a normal GFR response. Thus in normal subjects renal vasodilatory prostaglandins appear to be the final effector of the renal hemodynamic and albuminuric response to a meat meal. The prostaglandin increase is likely to be mediated under physiological conditions by a glucagon rise, which, however, has no effect per se on renal hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Ketone body metabolism: a physiological and clinical overview.
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Amino Acids↗
Sodium metabolism in insulin dependent diabetic patients. Role of insulin and atrial natriuretic peptide.
Acute insulin administration shows an antinatriuretic effect in normal man. Thus it can be postulated that insulin therapy resulting in circulating hyperinsulinemia can lead to sodium retention and in turn to hypertension in insulin dependent diabetes. Moreover it has been proved that atrial natriuretic peptide (ANP) plays a major role in modulating natriuresis in man. The aim of the present study was to investigate the relationship between insulin and ANP in modulating sodium metabolism in seven insulin dependent diabetic patients in comparison with eight normal control subjects at baseline and during a saline infusion (2 mmol/kg/90 min) at euglycemic blood levels. Diabetics received a subcutaneous insulin infusion (0.015 U/kg/hr) resulting in a two fold higher plasma free insulin levels (16 +/- 2 microU/ml) than in control subjects (7 +/- 2 microU/ml). During saline challenge sodium excretion rate increased by 29 +/- 6% in control patients and only by 6 +/- 0.7% in diabetic patients (p less than 0.01). At baseline ANP plasma concentrations were significantly higher in diabetic patients than in control subjects (diabetics = 37 +/- 8 pg/ml and controls = 21 +/- 3 (p less than 0.01). After saline challenge ANP concentration rose to 71 +/- 9 pg/ml in control subjects, whereas no significant change above baseline values was shown by diabetic patients.
Atrial Natriuretic Factor↗
Tubular Na+ handling in type I insulin-dependent diabetics during saline and ketone body infusion.
It has been reported that patients with type I insulin dependent diabetes mellitus (IDDM) are characterized by reduced Na+ excretion during water immersion and saline infusion and abnormal glomerulo-tubular balance. Aims of the present study were therefore to investigate firstly the fractional tubular Na+ reabsorption during saline infusion to clarify the altered tubular site and secondly the glomerulo-tubular balance during acute increase of glomerular filtration rate induced by sodium acetoacetate infusion in IDDM. During saline and euglycaemic glucose clamp, after an overnight fast, glomerular filtration rate, renal plasma flow, filtration fraction and plasma sodium were 99 +/- 15 ml min-1 1.73 m-2, 452 +/- 109 ml min-1 1.73 m-2, 0.23 +/- 0.04 and 142 +/- 8 mmol l-1 (Mean +/- SD) in 10 type I insulin dependent diabetic patients and 96 +/- 18, 452 +/- 87, 0.21 +/- 0.02, 143 +/- 2 in five matched normal subjects, respectively. The lithium and sodium clearances were significantly lower in diabetic patients than in normal subjects (23 +/- 5 ml min-1 1.73 m-2 vs 28 +/- 6, p less than 0.05 and 1.1 +/- 0.4 vs 1.6 +/- 0.3, p less than 0.01 respectively). The fractional lithium reabsorption was greater (0.77 +/- 0.04 vs 0.72 +/- 0.03, p less than 0.05) and the distal fractional sodium reabsorption smaller (0.22 +/- 0.04 vs 0.27 +/- 0.03, p less than 0.01) in the diabetic patients compared to the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetoacetates↗
Porcine and human insulin absorption from subcutaneous tissues in normal and insulin-dependent diabetic subjects: a deconvolution-based approach.
The mechanisms of sc insulin absorption are not understood, and models for interpreting in vivo data cannot be developed without gross simplification. To overcome this difficulty we developed a new approach which makes use of deconvolution analysis and does not require any model of the sc tissue. In five normal subjects and seven insulin-dependent diabetic (IDDM) patients endogenous insulin secretion was suppressed by means of a hypoglycemic glucose clamp procedure (approximately 2.8 mmol/L) sustained by a continuous insulin infusion (approximately 4 pmol/min.kg). A bolus injection of insulin (5.4 nmol) was administered iv, and plasma insulin concentrations were measured frequently for 2 h to assess iv insulin kinetics. Insulin then was injected sc in the abdominal region, and plasma insulin concentrations were measured for 8 h. Each subject was studied twice, with porcine and semisynthetic human insulin (Actrapid, Novo). The rate of insulin absorption was reconstructed by deconvolution from the plasma concentrations and iv insulin kinetic data. Linearity of the iv insulin kinetics, essential for deconvolution analysis, was confirmed by a dose-response study in the range of the measured concentrations (150-1800 pmol/L). In most instances, a two-compartment model was adequate to describe the iv response. The mean plasma insulin clearance rates were 15.5 +/- 1.9 (+/- SD) mL/min.kg (porcine) and 17.2 +/- 6.0 (human) in normal subjects and 20.7 +/- 8.8 (porcine) and 20.9 +/- 9.1 (human) in the IDDM patients. The rate of appearance of human insulin from sc tissue was faster than that of porcine insulin in both normal and IDDM subjects, but no significant differences were found in bioavailability, which was 55 +/- 12% (+/- SD; porcine) and 61 +/- 34% (human) in the normal subjects, and 84 +/- 28% (porcine) and 86 +/- 23% (human) in the IDDM patients. The rate of absorption and bioavailability were higher in the IDDM patients than in the normal subjects, a difference possibly related to increased sc blood flow in the IDDM patients. No differences were found with regard to glucose requirement values, normalized to plasma insulin concentrations, in agreement with the finding that the bioavailability of the two insulin species was similar.
Adolescent↗
Spontaneous emission in a double dielectric slab for C
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Journal Article↗
Ketone bodies increase glomerular filtration rate in normal man and in patients with type 1 (insulin-dependent) diabetes mellitus.
The purpose of this study was to investigate whether the administration of acetoacetic and hydrochloric acids in a group of control and Type 1 (insulin-dependent) diabetic patients influenced renal haemodynamics. Renal plasma flow increased from 657 +/- 88 to 762 +/- 81 ml X min-1. 1.73 m-2 in diabetic patients (p less than 0.01) and from 590 +/- 71 to 691 +/- 135 in control subjects (p less than 0.01). Glomerular filtration rate increased from 135 +/- 9 to 180 +/- 8 ml X min-1. 1.73 m-2 in diabetic patients (p less than 0.001) and from 117 +/- 8 to 145 +/- 7 in control subjects (p less than 0.01). Similar effects on renal haemodynamics, even if less pronounced, were observed with low dose acetoacetic but not with hydrochloric acid infusion. Total protein, beta 2-microglobulin but not albumin excretion rates were increased by acetoacetic acid. We conclude that an acute increase in blood concentration of ketone bodies within the range found in diabetic patients with poor metabolic control increases renal plasma flow and glomerular filtration rate both in control subjects and diabetic patients and causes a tubular proteinuria.
Acetoacetates↗
Glucose and ketone body turnover in carnitine-palmitoyl-transferase deficiency.
Most of the patients with carnitine-palmitoyl-transferase deficiency (CPT) show reduced levels of blood ketone bodies in the postabsorptive state. In the present study, we have evaluated ketone body and glucose kinetics in patients with CPT deficiency. Intermediate metabolites of carbohydrate and lipid metabolism have also been studied. Ketone body (KB) turnover was measured by means of sequential intravenous bolus injections of 3-14C acetoacetate and 3-14C D(-) 3-hydroxybutyrate in four patients with liver, platelet, and muscle deficiency of CPT system and in eight normal overnight fasting subjects. 6-3H glucose was also injected, along with 3-14C ketone bodies to measure glucose turnover rate. Three out of four CPT deficiency patients had normal KB turnover, despite a marked reduction in liver CPT activity. Only one subject, with severe defect of CPT activity in liver, showed a significantly reduced, but still present rate of de novo synthesis of acetoacetate and 3-hydroxybutyrate (40 and 51 mumol/m-2/min-1 respectively) in comparison with control subjects (103 +/- 14 and 157 +/- 22 mumol/m-2/min-1). Blood concentrations of dicarboxylic adipic and suberic acids were significantly higher in CPT deficiency patients (0.035 +/- 0.007 and 0.021 +/- 0.005, mmol/L respectively) than in control subjects (0.008 +/- 0.008 and 0.006 +/- 0.003 respectively). Basal glucose turnover was increased in CPT deficiency patients (505 +/- 13 mumol/m-2/min-1) in comparison with normal subjects (433 +/- 18 mumol/m-2/min-1; P less than .01) as well as clearance rates (127 +/- 3 mL/m-2/min-1 and 91 +/- 11 mL/m-2/min-1, respectively; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
3-Hydroxybutyric Acid↗
Glomerular filtration rate is increased in man by the infusion of both D,L-3-hydroxybutyric acid and sodium D,L-3-hydroxybutyrate.
A high glomerular filtration rate (GFR) is often found early in insulin-dependent diabetes mellitus (IDDM). It has been suggested that high circulating glucose, glucagon, and GH levels could play a role in this increase in GFR. On the other hand, patients with IDDM in poor metabolic control also have high circulating ketone body levels. This study was undertaken to determine whether exogenous D,L-3-hydroxybutyric acid at two infusion rates (40 and 30 mumol kg-1 min-1) for 180 min altered renal plasma flow (RPF), GFR, and the excretion rate of total protein, beta 2-microglobulin, and albumin in 11 normal (N) subjects and 11 IDDM patients in whom euglycemia was achieved and maintained using the insulin-glucose clamp technique. RPF and GFR were measured by a priming-continuous infusion of [125I]hippurate and [51Cr]EDTA, respectively. The 40 mumol kg-1 min-1 D,L-3-hydroxybutyric acid infusion increased RPF and GFR in both N and IDDM subjects. Mean RPF increased from 588 +/- 78 (+/- SD) to 706 +/- 129 mL min-1 1.73 m-2 in N and from 671 +/- 101 to 781 +/- 99 in IDDM. GFR increased from 121 +/- 11 to 151 +/- 15 ml min-1 1.73 m-2 in N and from 136 +/- 11 to 191 +/- 16 in IDDM. The filtration fraction also was significantly higher in IDDM than in N during the D,L-3-hydroxybutyric acid infusion. The 30 mumol kg-1 min-1 D,L-3-hydroxybutyric acid infusion increased RPF and GFR to a somewhat lesser extent in both groups. D,L-3-hydroxybutyric acid infusions increased the tubular reabsorption rate of ketone bodies and sodium. The increase in tubular sodium reabsorption rate was correlated significantly to that in the tubular ketone body reabsorption rate. A significant decrease in urinary pH was found during the D,L-3-hydroxybutyric acid infusion. D,L-3-Hydroxybutyrate sodium salt (30 mumol kg-1 min-1) also was infused in 5 of the 11 diabetic patients. A similar increase in GFR and RPF occurred. Both total protein and beta 2-microglobulin, but not albumin, excretion rates increased during D,L-3-hydroxybutyric acid (40 mumol kg-1 min-1) infusion in N and IDDM subjects. D,L-3-Hydroxybutyric acid infusion did not change plasma glucagon, GH, or renin activity.(ABSTRACT TRUNCATED AT 400 WORDS)
3-Hydroxybutyric Acid↗