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Biomedical subjects

L Jorfeldt

Publications and source records attributed to L Jorfeldt.

At least 37 records · Page 2Linked to original sources

Tricarboxylic acid cycle intermediates during incremental exercise in healthy subjects and in patients with McArdle's disease.

1. The importance of the level of tricarboxylic acid cycle intermediates (malate, citrate and fumarate) for energy transduction during exercise has been investigated in six healthy subjects and in two patients with muscle phosphorylase deficiency (McArdle's disease). 2. Healthy subjects cycled for 10 min at low (50 W), moderate [130 +/- 6 W (mean +/- SEM)] and high (226 +/- 12 W) work rates, corresponding to 26, 50 and 80% of their maximal O2 uptake, respectively. Patients with McArdle's disease cycled for 11-13 min at submaximal (40 W) rates, and to fatigue at maximal work rates of 60-90 W. 3. In healthy subjects, phosphocreatine was unchanged during low work rates, but decreased to 79 and 32% of the initial level during moderate and high work rates. In patients with McArdle's disease, phosphocreatine decreased to 82 and 34% of the initial level during submaximal and peak exercise. Muscle lactate increased in healthy subjects during exercise at moderate and high work rates, but remained low in patients with McArdle's disease. 4. In healthy subjects, tricarboxylic acid cycle intermediates were similar at rest and at low work rates (0.48 +/- 0.04 mmol/kg dry weight), but increased to 1.6 +/- 0.2 mmol/kg dry weight and 4.0 +/- 0.3 mmol/kg dry weight at moderate and high work rates. The tricarboxylic acid cycle intermediate level in patients with McArdle's disease was similar to that in healthy subjects at rest, but was markedly reduced during exercise when compared at the same relative intensity. The peak level of tricarboxylic acid cycle intermediates in patients with McArdle's disease was 22% of that in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Lactate metabolism and hypocarbic hyperventilation. An experimental study in piglets.

Hyperventilation has been reported to increase blood lactate levels. Uncertainty exists as to whether high lactate levels are caused by increased peripheral release or decreased hepatic uptake. Seven piglets were investigated during controlled normoventilation and 13 piglets during controlled hyperventilation. Blood was drawn from catheters in the femoral artery and vein and in the hepatic vein. Blood flow was measured in the femoral artery by an electromagnetic flow meter and in the splanchnic area by indocyanine green extraction. In addition, repeated muscle biopsies from the hind limb and back muscles were taken. The mean PaCo2 was 5.4 in the normoventilated and 3.5 kPa in the hyperventilated group. The average hind limb oxygen uptake was the same in both groups. The arterial blood lactate concentration was significantly higher (P = 0.03) in the hyperventilated group (2.6 mmol.l-1) as compared to the normoventilated group (1.5 mmol.l-1). However, the release of lactate from the hind limb, and the muscular content of lactate were the same in both groups. Similar and unchanged skeletal muscle contents of glucose-6-phosphate, fructose-1,6-diphosphate, alpha-glycerophosphate, pyruvate, citrate and ATP were recorded in both groups. The splanchnic region did not take up or release lactate at normal PaCO2, but released lactate after 120 minutes of hyperventilation. The results indicate that the increased concentration of lactate during hypocarbic hyperventilation was not caused by an increased peripheral release from the skeletal muscles of the pig but could be caused by an altered splanchnic turn-over of lactate.

Adenosine Triphosphate↗

Fat metabolism and its response to infusion of insulin and glucose in patients with advanced chronic obstructive pulmonary disease.

In order to investigate fat metabolism and the regulation of lipolysis and blood fuel metabolites by insulin, nine patients with chronic obstructive pulmonary disease (COPD) with chronic hypoxaemia and seven healthy control subjects of similar age were investigated by determination of the turnover rate of free fatty acids (TOR), using 1-14C-oleic acid as a tracer, and arterial concentrations of FFA, glycerol and 3-hydroxybutyrate. The measurements were performed in the basal state and during insulin and glucose infusion, aiming at euglycaemia at insulin levels of 50 and 100 mU l-1. The subjects' ages were 64 +/- 2.7 and 66 +/- 1.1 (mean +/- SEM) years in the COPD and control groups, respectively. TOR was 0.73 +/- 0.06 and 0.52 +/- 0.02 mmol min-1 (P < 0.05) in the basal state, 0.33 +/- 0.04 and 0.30 +/- 0.02 at an insulin level of 50 mU l-1 and 0.32 +/- 0.08 and 0.24 +/- 0.02 at an insulin level of 100 mU l-1, in the COPD and control groups, respectively. Arterial FFA concentration was 0.98 +/- 0.08 and 0.75 +/- 0.06 mmol l-1 (P < 0.05) in the basal state in the COPD and control groups, respectively. During the clamp, the decrease in FFA mirrored that in TOR. The results show that the state of lipolysis is increased in severe COPD patients with chronic hypoxaemia. Furthermore, the results suggest a reduced effect of insulin in lipolysis.

Aged↗

Insulin resistance is not exhibited by advanced chronic obstructive pulmonary disease patients.

We have previously reported increased blood glucose concentrations and skeletal muscle glycogen depletion in severe COPD patients with chronic respiratory failure. In order to see if insulin resistance exists in severe COPD, we investigated nine patients with advanced COPD with chronic hypoxaemia and seven healthy control subjects of similar age, using the euglycaemic hyperinsulinaemic glucose clamp technique. We could not demonstrate a subnormal intravenous glucose requirement in response to insulin when maintaining euglycaemia in the COPD patients with chronic hypoxaemia. This indicates that the net metabolism of glucose in COPD patients with chronic hypoxaemia is not resistant to insulin.

Blood Gas Analysis↗

A mathematical model for measuring blood flow in skeletal muscle with the microdialysis ethanol technique.

A theoretical analysis of the microdialysis ethanol technique in skeletal muscle is presented, and a model governing the transport of ethanol from the microdialysis probe to the capillaries in the muscle tissue is proposed. The model is derived under the assumption of a steady-state situation, and an analytical solution is found for the outflow-to-inflow ratio of ethanol in the perfusate. Theoretically calculated results are compared with experiments, and for at least one of the two probe types used good agreement is achieved in a wide range of blood flow and perfusate flow rates. The main uncertainty factor in the theoretical calculations is the diffusivity of ethanol in muscle tissue, and the value for best agreement between theory and experiments has been used. Error estimates show that for a constant relative error in the outflow-to-inflow ratio of ethanol in the perfusate, low perfusate flow rates give better predictions of the blood flow.

Animals↗

Metabolic enzyme activity in the quadriceps femoris muscle in patients with severe chronic obstructive pulmonary disease.

Eighteen patients with severe COPD and seven healthy control subjects 64.0 +/- 2.2 and 66.8 +/- 1.4 yr of age, respectively (mean +/- SEM), were investigated. Arterial blood gas analysis, dynamic lung volumes, and muscle biopsy specimens from the quadriceps femoris muscle were performed. The muscle biopsies were analyzed for citrate synthase (CS), succinic acid dehydrogenase (SDH), 3-hydroxyacyl-CoA dehydrogenase (HAD), phosphofructokinase (PFK), and lactate dehydrogenase (LDH) activities and related to protein content. The PFK activity was higher in the COPD group than in the control group (+34%, p < 0.05). CS showed a group difference in the opposite direction (-29%, p < 0.05). LDH activity followed PFK and tended to be higher in the patient group (+27%, NS), whereas SDH (-31%, NS) and HAD (-28%, NS) mirrored the CS results. Muscle protein concentration tended to be lower in the COPD group (-14%, NS). There were no significant changes in enzyme activity after 7 mo of long-term oxygen therapy (n = 6). These results indicate adaptation in the form of augmented glycolysis (PFK), and decreased aerobic metabolism (CS) in the quadriceps femoris muscle in patients with advanced COPD.

Citrate (si)-Synthase↗

Muscle blood flow during intermittent exercise: comparison of the microdialysis ethanol technique and 133Xe clearance.

1. Local skeletal muscle blood flow was monitored using the microdialysis ethanol technique and 133Xe clearance during intermittent isometric contractions (5 s on/10 s off) of the thigh at 0-60% of the maximal voluntary isometric contraction force. 2. A linear increase in blood flow over a 25-fold range was detected using both 133Xe clearance and the microdialysis ethanol technique. 3. The median correlation coefficient between percentage maximal voluntary isometric contraction force and the ethanol outflow/inflow ratio, a marker of blood flow, was r = -0.98 (-0.94 to -0.99) (median and range, n = 6). The corresponding correlation coefficient for 133Xe clearance was r = 0.97 (0.92-0.98), the correlation coefficient between the ethanol outflow/inflow ratio and 133Xe clearance being r = -0.92 (-0.89 to -0.94). 4. Dialysate glucose concentration, although affected by blood flow, was not always significantly correlated with blood flow changes (r = 0.70; 0.51-0.95). 5. It may be concluded that the ethanol technique provides a valid measure of changes in local skeletal muscle blood flow. The data furthermore show that a linear increase in thigh skeletal muscle blood flow exists during the studied protocol of intermittent isometric contractions.

Adult↗

Improved glucose metabolism after subtotal pancreatectomy for pancreatic cancer.

Diabetes occurs frequently in patients with pancreatic cancer. To investigate the impact to tumour removal, seven patients were studied before and after 85 per cent subtotal pancreatectomy for adenocarcinoma of the pancreas. The frequency of diabetes was determined by the oral glucose tolerance test. Fasting levels of C peptide and insulin were measured in plasma, and insulin secretion was investigated by hyperglycaemic glucose clamp and glucagon stimulation. Six of the seven patients were diabetic before surgery and four required insulin treatment. Improvements in diabetic status and glucose metabolism were found in all seven patients after operation, as demonstrated by increased glucose metabolic capacity during hyperglycaemia. This occurred despite a postoperative reduction in insulin secretion and is explained by the observed augmentation of whole-body insulin sensitivity after surgery. A diabetogenic factor may be produced by pancreatic adenocarcinoma that may be responsible, directly or indirectly, for the high frequency of diabetes in patients with pancreatic cancer.

Adenocarcinoma↗

The care and handling of peripheral intravenous cannulae on 60 surgery and internal medicine patients: an observation study.

The purpose of this study was to analyse the actual routines surrounding the use of peripheral cannulae and the occurrence of complications. Thirty surgery patients and 30 internal medicine patients were observed daily at a medium-sized hospital. The patients were followed from the time the cannula was inserted until after withdrawal and until both the insertion site and the vein were free from pain. The results showed that most of the cannulae were placed on the upper side of the hand and sizes most frequently used were 1.0 and 1.2 mm. The fixation was unsatisfactory in 23 cases already after the second day. Twenty-three cannulae were removed after 24 hours. Thirty-seven (62%) patients were stated to have thrombophlebitis phlebitis in different degrees. Only seven cannulae fulfilled the criteria for good cannula care and handling. The frequency of complication was especially high when fructose-glucose, antibiotics or anticoagulants were given. There was no documentation in the patient record, according to current laws in Sweden. The complications observed were redness, swelling, haematoma, subcutaneous swelling and suppurating infection. The study showed that the longer the cannula had been in situ, the greater were the complications (very distinct after 24 hours). The care and handling was unsatisfactory to very unsatisfactory in 52% of the cases. Complications can last for a very long time. In this research, pain was noted up to 5 months after the cannulae were removed.

Adult↗

Interstitial glucose and lactate balance in human skeletal muscle and adipose tissue studied by microdialysis.

1. Microdialysis was used to gain insight into the substrate exchanges in the interstitial space of skeletal muscle and adipose tissue. Probes were inserted in the quadriceps femoris muscle and para-umbilical subcutaneous adipose tissue of thirteen subjects and microdialysis was performed at different flow rates (1-4 microliters min-1) and during changes in tissue blood flow. 2. When ethanol (5 mM) is included in the perfusion solution, the ethanol clearance from the probe is a measure of tissue blood flow. Blood flow changes induced by adenosine or vasopressin perfusion, by exercise or by circulatory occlusion resulted in ethanol clearance values of 69-139% of the basal level. The ethanol clearance was higher in skeletal muscle than in adipose tissue (32-62%, P < 0.001), a difference compatible with a higher blood flow in muscle tissue. 3. The fraction of the interstitial glucose concentration that was recovered with the microdialysis was similar in skeletal muscle (the absolute values being 1.70 +/- 0.14 mM at 1 microliter min-1 and 0.59 +/- 0.05 mM at 4 microliters min-1) and adipose tissue (1.89 +/- 0.20 mM at 1 microliter min-1; 0.54 +/- 0.05 mM at 4 microliters min-1) and correlated inversely with the tissue ethanol clearance, both in the basal state and during changes in tissue blood flow (muscle: r = -0.56 to -0.67; adipose tissue r = -0.72 to -0.95). Coefficients of variation were 6-8% (glucose) and 11-16% (lactate) and were similar during isometric exercise. The reproducibility of the technique (comparison of two contralateral probes; perfusion flow rate 4 microliters min-1) was 5.3-8.3% (ethanol) and 23.9-20.8% (glucose) in muscle (n = 6) and adipose tissue (n = 4) respectively. 4. The skeletal muscle dialysate lactate concentration (1 microliter min-1: 1.16 +/- 0.2 mM) was higher than in adipose tissue (0.76 +/- 0.08 mM, P < 0.05), where the absolute amount of lactate that could be removed from the tissue (at 4 microliters min-1) was only half of that in skeletal muscle (0.8 +/- 0.11 vs. 1.76 +/- 0.23 nmol min-1, P < 0.05). The dialysate lactate level was not affected in either tissue by large changes in the interstitial glucose concentration indicating that in neither tissue is blood glucose a significant source of lactate formation. 5. The blood flow effects on the dialysate glucose concentration are the likely consequence of probe glucose drainage artificially shifting the balance between the supply and consumption of interstitial glucose.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗

Pancreatic cancer is associated with impaired glucose metabolism.

OBJECTIVE: To investigate glucose metabolism and insulin secretion on patients with pancreatic cancer compared with healthy control subjects. DESIGN: Open study. SETTING: Linköping University Hospital, Sweden. SUBJECTS: 44 consecutive patients referred for radical operations for pancreatic carcinoma, and eight healthy age and sex matched volunteers. INTERVENTIONS: Hyperglycaemic glucose clamp in 36 of patients and all volunteers. MAIN OUTCOME MEASURES: Glucose tolerance according to WHO criteria, plasma insulin and C-peptide concentrations, and insulin secretion measurements both during hyperglycaemia and after stimulation by glucagon. RESULTS: Thirty-three patients (75%) had either impaired glucose tolerance or diabetes. Fasting insulin concentrations were raised in the non-insulin-requiring diabetic patients, but similar in the insulin-requiring group compared with healthy control subjects and patients with normal glucose tolerance. In neither diabetic group was insulin secretion affected during hyperglycaemia. After stimulation with glucagon, insulin secretion increased in non-insulin-requiring diabetic patients but remained unchanged in those who required insulin. Glucose metabolic capacity and whole body insulin sensitivity were reduced in patients with diabetes and with impaired glucose tolerance, and the reduction was more pronounced in diabetic patients. CONCLUSIONS: There is a high incidence of impaired glucose tolerance and diabetes in patients with pancreatic cancer, which cannot be explained by impaired secretion of insulin. Other factors that reduce insulin sensitivity seem to have a role in the development of diabetes in this group of patients.

Adenocarcinoma↗

Randomized, controlled study evaluating effects of branched chain amino acids and alpha-ketoisocaproate on protein metabolism after surgery.

The effect of nutritional supplementation with branched chain amino acids or the ketoacid alpha-ketoisocaproate on protein metabolism after surgery was studied in 24 patients with gastrointestinal cancer. They were randomized to receive one of three nutritional regimens. All patients received a balanced amino acid solution and group 1 (n = 8) received no further supplements, group 2 (n = 8) received supplementation with alpha-ketoisocaproate (17 g day-1) and group 3 (n = 8) received a branched chain solution including leucine, isoleucine and valine, corresponding to 3.3 g nitrogen day-1. Plasma albumin, prealbumin, fibronectin and serum urea concentrations, nitrogen balance and 3-methylhistidine release from the leg and its excretion in the urine were measured. Albumin and prealbumin concentrations fell after surgery in all groups, and fibronectin levels fell in group 2 (P less than 0.001). In group 2 there was also a significant increase in serum urea concentration after operation (P less than 0.05). Cumulative nitrogen balance after 3 days was -5.6 g (group 1), -3.8 g (group 2) and -1.7 g (group 3). The release of 3-methylhistidine (nmol 100 g-1 min-1) from the leg after operation, following an overnight fast, was -0.42 (group 1), -0.51 (group 2) and -0.66 (group 3). During infusion the release was -0.56, -0.99 and -0.81, respectively. A balanced amino acid solution with an adequate energy supply has an optimal nitrogen-sparing effect. Branched chain amino acids or alpha-ketoisocaproate did not improve nitrogen balance or reduce protein degradation.

Amino Acids, Branched-Chain↗

Gas exchange as monitored in mixed venous and arterial blood during experimental cardiopulmonary resuscitation.

Nineteen anaesthetized piglets were investigated. After catheterization and a stabilization period, ventricular fibrillation was induced with a transthoracic DC shock, after which a 10-min period of cardiopulmonary resuscitation (CPR) took place. CPR included manual chest compression and mechanical ventilation with pure oxygen. After 1 min of CPR, an infusion of alkaline buffer was begun and completed within 5 min. A total of 50 mmol of either sodium bicarbonate (n = 6) or tris buffer mixture (n = 7) were given. These two groups were compared with a third control group (n = 6) receiving the same volume of normal saline. After 8 min of CPR all animals were given 0.5 mg adrenaline i.v., and after 10 min DC shocks were used to revert the heart back to normal sinus rhythm. Our results demonstrate that blood flow and not ventilation is the limiting factor for the efficient disposal of CO2 during CPR. This also applied when the demand for CO2 transport was increased by administration of sodium bicarbonate. The respiratory exchange ratio increased 1.9-fold, indicating that the transport of carbon dioxide was less affected than that of oxygen. The estimated alveolo-arterial oxygen tension difference, shunt, and overall ventilation/perfusion ratio increased, creating an inverse hyperbolic relationship between arterial PCO2 and PO2. The difference between mixed venous and arterial PCO2 correlated well to the mixed venous PCO2, implying more efficient pulmonary elimination of PCO2 when the mixed venous PCO2 was high. Pulmonary gas exchange during CPR appears to be independent of alkaline buffer therapy in the form of sodium bicarbonate or tris buffer mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hypoglycaemia and cardiac arrhythmias in patients with type 2 diabetes mellitus.

Improved blood glucose control by insulin treatment in patients with Type 2 (non-insulin dependent) diabetes mellitus increases the risk for hypoglycaemic episodes. Our objective was to investigate if hypoglycaemia causes electrocardiographic changes and cardiac arrhythmias in patients with Type 2 diabetes. Six insulin-treated patients with Type 2 diabetes and no known cardiac disease took part in the study. Hypoglycaemia was induced by insulin infusion aiming at a plasma glucose less than or equal to 2.0 mmol l-1 or hypoglycaemic symptoms. All patients experienced hypoglycaemic symptoms. The median lowest arterial plasma glucose was 2.0 mmol l-1. Arterial plasma adrenaline concentration increased from 0.4 +/- 0.1 (mean +/- SE) to 6.9 +/- 0.3 nmol l-1 (p less than 0.001) while serum potassium was lowered from 4.1 +/- 0.3 mmol l-1 to 3.5 +/- 0.2 mmol l-1 (p less than 0.001). The heart rate increased significantly during hypoglycaemia except in one patient who developed hypoglycaemic symptoms and a severe bradyarrhythmia at a plasma glucose of 4.4 mmol l-1. One patient developed frequent ventricular ectopic beats during hypoglycaemia while four patients showed no arrhythmia. ST-depression in ECG leads V2 and V6 was observed during hypoglycaemia in five patients (p less than 0.05) and four patients developed flattening of the T-wave. In conclusion, the study supports the hypothesis that hypoglycaemia in patients with Type 2 diabetes may be hazardous by causing cardiac arrhythmias.

Arrhythmias, Cardiac↗

The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis.

We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mM did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]collected dialysate/[ethanol]infused perfusion medium), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow-chamber, this ratio changed in a flow-dependent way in the external flow range of 5-20 microliters min-1. The ethanol outflow/inflow ratio in vivo was significantly (P less than 0.001) increased (to a maximum of 127 +/- 2.8% and 144 +/- 7.4% of the baseline, mean +/- SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P less than 0.001) reduced (to 62 +/- 6.4% and 43 +/- 4.4% of baseline) with increases in blood flow during external heating or local 2-chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P less than 0.01) and consequently decreased (to 46 +/- 7.6% and 56 +/- 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 +/- 32.5% and 262 +/- 16.7% of baseline) following heating and 2-chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2-fold, P less than 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments.

2-Chloroadenosine↗

Absorption of irrigating fluid during transurethral prostatic resection as measured by ethanol, radioisotopes, and regular-interval monitoring.

Ethanol monitoring is a novel noninvasive method for immediate detection of absorption of irrigating fluid during transurethral prostatic resection. Its accuracy was evaluated during thirteen resections using 5% mannitol +2% ethanol as the irrigating fluid. The ethanol concentration in the expired breath correlated strongly with the degree of absorption of intravascular irrigating fluid as determined by a radioisotope technique, and fluid volume measurements, and with the changes in the serum sodium concentration. Extravascular absorption of the irrigating fluid resulted in prolonged elevation of the ethanol concentration and gave smaller changes in the serum sodium concentration.

Absorption↗

Use of ethanol as marker substance to increase patient safety during transurethral prostatic resection. Screening investigation of irrigating fluid absorption in four hospitals and comparison of experienced and inexperienced urologists.

Of 472 patients at four different hospitals electively undergoing transurethral resection of the prostate (TURP), 192 received Sorbitur as an irrigating fluid with 2% ethanol (w/v) as a marker. Using a breath analyzer (Alcol-meter), the amount of ethanol in expired air was measured regularly during the operation to detect the absorption of irrigating fluid. The ethanol concentration in expired air was plotted against time. The time-ethanol concentration product was used as a measurement of absorbed ethanol marked irrigating fluid. A unit of more than 2.5 was considered to be a major absorption with possible clinical significance. This criterion was fulfilled in 24 percent of the patients. Postoperative serum sodium was shown to decrease more in patients with major absorption than in patients with minor absorption in comparison to preoperative values. The weight of resected tissue and the bleeding per resected gram of tissue was higher in the patients with major absorption, but the resected tissue per operating time was the same in both groups. The experienced urologists had as many patients with absorption as did the inexperienced ones. Ethanol-marked irrigating fluid is a simple, safe, noninvasive, rapid, and cheap method of detecting absorption of irrigating fluid thus increasing patient safety during TURP. This method indicates absorption before clinical signs and symptoms of the TUR syndrome occur. It also provides an easy method for estimating the frequency of absorption of irrigating fluid routinely in clinical work.

Absorption↗