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Biomedical subjects

J Ditzel

Publications and source records attributed to J Ditzel.

At least 91 records · Page 5Linked to original sources
PubMed1976

Clofibrate in type II hyperlipoproteinemia.

As a part of a double-blind randomized study, the safety and the lipid- and uric acid-lowering effect of clofibrate have been evaluated in 28 patients with type II hyperlipoproteinemia (HLP). A highly significant reduction of serum cholesterol occurred in type IIa and of serum triglyceride and choelsterol in type IIb HLP throughout the 60-week observation period (p less than 0.01). Of the patients with types IIa and IIb HLP, 65% had at least a 25% reduction of serum cholesterol. Uric acid was significantly reduced only during the first period of treatment (p less than 0.05). In the laboratory measurements concerning safety, a persistent, slight reduction was observed in Hb, hematocrit and alkaline phosphatase. No significant clinical side-effects were noted. Clofibrate is considered effective as a lipid-lowering agent in many cases of type II HLP.

Adult↗
PubMed1976

Oxygen transport impairment in diabetes.

Oxyhemoglobin dissociation curves (ODC) from zero to full saturation were developed from tests performed on whole blood from various groups of diabetic and nondiabetic healthy subjects. P50 at in-vivo pH was slightly but significantly lower than normal in ambulatory nonacidotic, uncomplicated juvenile diabetics (26.0 vs. 27.3 mm. Hg, P less than 0.001), despite increased red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations in diabetic erythrocytes (15.0 vs. 13.7 mumole/gm. Hb, P less than 0.001). This combination of changes is in keeping with the presence of increased proportions of hemoglobin AIc in insulin-treated diabetics. The position of the ODC was positively correlated with the 2,3-DPG concentration (P less than 0.01), which varied in response to fluctuations in plasma concentration of inorganic phosphate (Pi) (P less than 0.001). Optimal metabolic control may lead to a normalization of the ODC in association with increased concentrations of red cell 2,3-DPG and P. When the diabetes was uncontrolled, the ODC was usually unchanged during the acidotic phase because the lowered pH balanced the effect of diminished 2,3-DPG concentration on the ODC. After correction of acidosis, the disproportion between erythrocyte 2,3-DPG and pH became quite prominent, accompanied by a corresponding fall in P50 (21.0 vs. 26.1 mm. Hg, P less than 0.001). Following ketoacidosis, with a persistently lowered Pi, it may take up to one week for 2,3-DPG to return to an approximately normal level, and the P50 will be impaired for the same period. A diphosphonate (EHDP) known to enhance tubular phosphate reabsorption in man was given to nonacidotic insulin-treated diabetic and healthy volunteers for 28 days. It caused a significant increase in mean Pi and P50 in both healthy and diabetic subjects (r = 0.58, P less than 0.01). When a dietary supplement of dibasic calcium phosphate was given to diabetic subjects for 28 days, a significant increase in P50 also occurred (25.2 vs. 27.2 mm. Hg, P less than 0.001). It is recommended that the diabetes diet be supplemented by dibasic calcium phosphate to prevent the inhibitory effect of a low concentration of Pi on red cell oxygen delivery.

Biological Transport, Active↗
PubMed1975

The oxygen transport system of red blood cells during diabetic ketoacidosis and recovery.

Daily evaluations of 8 newly detected ketoacidotic diabetics showed the Bohr-effect of haemoglobin to be decreased by 50% while erythrocyte 2,3-DPG was decreased below 10 mumoles/g Hb. 2,3-DPG correlated strongly with pH during acidosis and with plasma inorganic phosphate (Pi) subsequently to the first insulin administration. Oxygen affinity of haemoglobin, measured as P50 act pH, was unchanged in ketoacidosis compared to the time, however, P50 act pH fell striking (p less than 0.001) and remained decreased up to 7 days depending upon the resynthesis of 2,3-DPG in relation to Pi. The Hill-coefeficient in reflecting the slope of the oxygen dissociation curve was diminished in ketoacidosis (p less than 0.005), and decreased further after pH-normalization (p less than 0.005). There was a close association of n with 2,3-DPG (p less than 0.001) and additionally with Pi at 2,3-DPG-levels below 10 mumoles/g Hb. Based on these findings a decreased erythrocyte oxygen release of one fifth during acidosis and more than one third after pH-correction can be hypothesised. In view of the intimate relation of Pi to the oxygen transport system it is suggesed that treatment of ketoacidosis should include Pi-sugstitution.

Adolescent↗
PubMed1975

The problem of tissue oxygenation in diabetes mellitus.

In order to study the determining factors for oxygen transport the oxyhaemoglobin dissociation curve (ODC), red cell 2,3-diphosphoglycerate (2,3-DPG), and plasma inorganic phosphate were estimated in insulin-requiring juvenile and adult diabetics in various conditions of metabolic control. 2,3-DPG has been shown to vary much more in diabetics than in normals, depending upon the state of metabolic control. These fluctuations of 2,3-DPG are mediated by variations in plasma inorganic phosphate as indicated by a close correlation. While 2,3-DPG was markedly decreased in diabetic ketoacidosis, it tended to be increased in ambulatory, non-acidotic patients. Since in the non-acidotic patients the oxygen-carrying capacity, i.e. the haemoglobin concentration was simultaneously elevated, these findings suggest the presence of relative tissue hypoxia in diabetes. Both in non-acidotic and in ketoacidotic patients there was a strong correlation between the amount of 2,3-DPG and the P50 at actual pH as an experssion of the oxygen affinity of haemoglobin. In order to guarantee an optimal erythrocyte oxygen release in diabetics the content of red cell 2,3-DPG and plasma inorganic phosphate should be higher than normal.

Adolescent↗
PubMed1975

Oxygen affinity of haemoglobin and red cell 2,3-diphosphoglycerate in childhood diabetes.

Red cell 2,3-diphosphoglycerate (2,3-DPG) and the oxygen haemoglobin dissociation curve (ODC) were determined in 32 ambulatory, non-acidotic diabetic children and in 49 healthy children. Despite the fact that the diabetic children had, on average, an increased haemoglobin concentration, their erythrocytes contained significantly more 2,3-DPG than normal. Both in diabetic and in healthy children a negative relationship was found between the content of 2,3-DPG and the haemoglobin concentrations. No relationship was present between the plasma glucose and the 2,3-DPG concentration. The concentration of plasma inorganic phosphate (Pi) in the diabetic children was significantly higher than in the control children, and for all children there was a significant relationship between the 2,3-DPG and the Pi. In the diabetics 2,3-DPG was positively correlated to the P50 (7.40) and to the P50 (in vivo ph) of the ODC. However, despite the significant increase in 2,3-DPG among the diabetic children the average P50 (7.40) and P50 (in vivo pH) was not increased as compared with the control children. The inhibitory factor preventing the oxygen affinity from decreasing among the diabetics was strongly correlated to an increase in the mean corpuscular haemoglobin concentration. The result of this study suggests the presence of an increased amount of haemoglobin fraction with high oxygen affinity (haemoglobin Alc) in the red cells of juvenile diabetics.

Adolescent↗
PubMed1975

The problems of tissue oxygenation in diabetes mellitus. III. The "three-in-one concept" for the development of diabetic microangiopathy and a rational approach to its prophylaxis.

Evidence for a causative relationship between prolonged tissue hypoxia and diabetic retinopathy and glomerulosclerosis are presented. Based on the assumption that one of the most fundamental requirements for optimal cellular metabolism is a constant cellular oxygen tension, the "three-in-one concept" for the development of diabetic microangiopathy is formulated. The term "three-in-one" is employed because this concept partly or completely includes "the glycoprotein-", "the hypoxia-", and "the growth hormone hypothesis". Diabetics show evidence of variability in the tissue oxygen availability/demand ratio which is compensated by three self-regulating factors: 1) an increase in local flow, 2) an increase in red cell 2,3-DPG leading to a shift to the right of the oxyhaemoglobin dissociation curve, and 3) an increase in the oxygen-binding capacity or the haemoglobin concentration. The level of plasma inorganic phosphate (Pi) is of importance in maintaining high 2,3-DPG levels. However, since Pi fluctuates depending upon changes in the control of diabetes, the regulatory mechanism of the 2,3-DPG modulated unloading of oxygen from the erythrocytes often becomes insufficient, and therefore in poorly regulated diabetics with less than optimal 2,3-DPG levels, the main load of compensation against tissue hypoxia is placed on an adjustment in the microcirculation of the organ involved. However, in order for the microvascular dilatation to occur, the cells must experience a hypoxic stimulus. The summation of the infinite number of discrete and occasionally pronounced hypoxic injuries to the tissue cells in association with the adverse effect of local vasodilatation with increased plasma permeation through the vessel walls might over the years lead to diabetic microangiopathy. Based on this theory the high level of Pi in diabetes becomes of particular significance. Our experience with a high phosphate diabetes diet in the treatment of diabetics is presented. This dietary regimen leads to a significant increase in the oxygen release capacity of the erythrocytes, suggesting an improvement in tissue oxygenation, and may therefore become of value in the prophylaxis of diabetic microangiopathy.

Blood Viscosity↗
PubMed1975

The problem of tissue oxygenation in diabetes mellitus. I. Its relation to the early functional changes in the microcirculation of diabetic subjects.

The underlying cause leading to the reversible functional changes in the microcirculation of insulin-dependent diabetic subjects early during the disease prior to any clinical signs of retinopathy and nephropathy (functional microangiopathy) is discussed. It is suggested that the initial microvascular dilation observed in diabetics is due to an autoregulatory response to relative tissue hypoxia providing an increased tissue perfusion in order to improve tissue oxygen delivery. Supporting evidence for this suggestion is derived from the findings that diabetics simultaneously may show increased tissue oxygen consumption and decreased ability of the circulating blood to release oxygen to the tissues. The latter defect is likely to be caused by two interrelated factors: 1. an increased proportion of haemoglobin A1c with high oxygen affinity, and 2. difficulties of maintaining a sufficiently high concentration of plasma inorganic phosphate in order to provide an optimal 2,3-diphosphoglycerate (2,3-DPG) content in the erythrocytes. The basal oxygen demand of diabetics may fluctuate even within a few hours dependent upon the state of metabolic control and is increased at times of poor regulation. Hence, diabetics may suffer from innumerable cellular hypoxic injuries, which during the first years of the disease are counteracted in the microcirculation by an autoregulatory response. These microvascular reactions associated with increased plasma permeation may over the years be of major importance for the development of the degenerative microangiopathy in diabetes.

Diabetes Mellitus↗