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Biomedical subjects

J Kofstad

Publications and source records attributed to J Kofstad.

At least 19 recordsLinked to original sources

Vitamin D deficiency, bone mineral density and weight in patients with advanced pulmonary disease.

OBJECTIVE: To study the influence of underweight, body composition and vitamin D deficiency on bone mineral density in patients with advanced pulmonary disease. DESIGN: Cross-sectional study with time span for inclusion set at 5 years. SETTING: The clinical work and biochemical analyses were carried out at Rikshospitalet University Hospital, Norway. Analyses for vitamin D metabolites and bone markers were carried out at Aker University Hospital, and bone measurements at Clinic of Osteoporosis. SUBJECTS: Seventy-one candidates for lung transplantation (63% chronic obstructive pulmonary disease, 42 underweight and 29 normal weight) were included. MAIN OUTCOME MEASURES: Body composition, bone mineral density at lumbar spine and femur neck, serum concentration of calcidiol and vitamin D intake. RESULTS: Subnormal calcidiol levels were present in 52% of the underweight patients and 69% of the normal-weight patients. The resulting models of linear regression showed that for the lumbar spine T scores model, the total variation of 16.7% was explained by group (underweight/normal weight), sex and age. For the femur neck T scores model, the total variation of 20.4% was explained by the interaction of underweight and vitamin D deficiency (with borderline significance) and by arm muscle circumference percentage of standard. In patients with normal calcidiol levels, the median intake of vitamin D was 17 microg in the underweight patients and 11 microg in the normal-weight patients. CONCLUSIONS: Vitamin D deficiency was common in both underweight and normal-weight patients, but only in the underweight patients, an association between vitamin D deficiency and reduced femur neck T scores was indicated.

Adult↗

Base excess: a historical review-has the calculation of base excess been more standardised the last 20 years?

Base excess blood, cBase(B), was introduced in the late 1950s by Ole Siggaard-Andersen to quantify the non-respiratory component in acid-base imbalance. Schwarz and coworkers in Boston argued that cBase(B) was not independent of pCO2 in vivo. Siggaard-Andersen introduced later the modified base excess, cBase(ecf), which has also been called standard base excess. Twenty years ago, on the 5th Meeting of the IFCC Expert Panel on pH and Blood Gases in Copenhagen, I showed that AVL, Corning (now Bayer), Instrumentation Laboratory (IL) and Radiometer had quite different algorithms for calculating cBase(B). All four used at least pH, pCO2 and ctHb for the calculation, IL used in addition pO2. I simulated 81 acid-base disturbances and calculated cBase(B) from the different algorithms. The calculations showed different values between different instruments, in particular in metabolic alkalosis. I proposed that the Expert Panel should work towards better standardisation in the calculation of cBase(B). If we look at the algorithms in use today for calculating cBase(ecf), the algorithms are not so complicated as the algorithms for cBase(B) and they are more uniform for all the manufacturers. This standardisation has led to the increased and effective use of cBase(ecf) in the clinical work.

Acid-Base Imbalance↗

Tapering off prednisolone and cyclosporin the first year after renal transplantation: the effect on glucose tolerance.

BACKGROUND: Glucose intolerance is an untoward side effect of some immunosuppressive and anti-hypertensive drugs. The primary aim of the present prospective observational study was to test the hypothesis that tapering off prednisolone and cyclosporin (CsA) the first year after transplantation may have beneficial effects on glucose tolerance in renal transplant recipients. METHODS: Ninety-one non-diabetic recipients were included, and 87 patients underwent a 75 g oral glucose tolerance test both 10 weeks and 1 year after renal transplantation. The change over time in 2-h blood glucose was compared with a number of variables potentially influencing glucose tolerance. RESULTS: The proportion of glucose intolerant recipients was reduced from 55 to 34% during the study. Univariate linear regression analysis showed a significant association between the reduction in daily prednisolone dose down to 5 mg and decline in blood glucose (P=0.001), whereas weight gain was associated with increasing blood glucose (P=0.031). Each 1-mg reduction of prednisolone dose leads to an estimated decline in 2-h blood glucose of 0.12 mmol/l based on the multiple linear regression model (P=0.003). Twelve out of 22 patients with post-transplant diabetes mellitus (PTDM) at baseline improved to normal or impaired glucose tolerance. Ten PTDM-subjects who remained diabetic 1 year after transplantation had lower serum insulin levels during the oral glucose challenge, and five patients treated with anti-diabetic drugs at baseline required hypoglycaemic drugs also at follow up. The decline in CsA level of 100 microg/l and the lower number of patients treated with beta-blockers at follow-up, did not alter glucose tolerance significantly. CONCLUSIONS: Tapering off prednisolone, but not CsA, significantly improves glucose tolerance during the first year after renal transplantation.

Adult↗

A study of intensified dietary support in underweight candidates for lung transplantation.

BACKGROUND: No data is available on dietary intervention in candidates for lung transplantation and on the effect of different strategies for dietary support in this cohort. AIM: We therefore wanted to evaluate the effects of intensified nutritional support compared with simple support on energy intake and nutritional status. METHOD: Our participants were underweight (n = 42) and normal-weight (control group, n = 29) candidates for lung transplantation. The underweight patients were randomized into two groups. Group A received intensified dietary counselling, ready-made liquid nutritional supplements free of charge and regular follow-ups, while group B received only one session of individual dietary counselling, no supplements and no follow-ups. RESULTS: The mean intervention time was 21 weeks. Groups A and B both increased their energy intake and gained weight. Group A increased their energy intake from a median of 8.7 to 10.1 MJ (p < 0.01 compared with the control group after intervention) and gained a mean of 2.9 kg body weight (95% CI 1.2; 4.7, p = 0.005 compared with the control group), while group B increased from 7.4 to 10.8 MJ (p = 0.005) and gained 2.3 kg (1.2; 3.3, p = 0.002). Only group B increased their fat-free mass. In this group, an increase in O(2) saturation and a decrease in PaCO(2) were suggested. None of the groups improved its physical performance. CONCLUSION: In candidates for lung transplantation we were unable to confirm the hypothesis that intensified nutritional support compared with a simple support increased compliance. Both groups achieved the goal for energy intake and gained weight.

Adult↗

Serum amino acids in relation to nutritional status, lung function and energy intake in patients with advanced pulmonary disease.

Malnutrition, hypoxia and energy deficit may affect protein metabolism. We wanted to evaluate the cross-sectional association between serum amino acids and fat-free mass in a group of hypoxic patients. We also wanted to explore, in the same group of patients, whether the blood amino-acid pattern could possibly be influenced by differences in lung function and energy intake. Serum amino acids were measured in 71 hypoxic underweight and normal-weight patients with advanced pulmonary disease and related to the fat-free-mass index, arterial oxygen (PaO2) and carbon dioxide tension (PaCO2), forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1) and energy intake. Only one amino acid (aspartic acid) remained significantly correlated to the fat-free-mass index after adjustments for age and sex (beta = -0.30, P=0.011). None of the amino acids were significantly correlated to PaO2 but alanine was significantly negatively correlated to PaCO2 (beta = -0.46, P<0.001), phenylalanine to FVC1 (beta = 0.52, P=0.001) and tyrosine to FVC (beta = 0.36, P=0.008). Citrulline and tryptophan were significantly correlated to energy intake (beta = 0.32, P=0.008; beta=0.37, P=0.009 respectively). In conclusion, there was no convincing association between fat free mass and serum amino acids. The negative effect of hypercapnia and reduced lung function on some serum amino acids was suggested and some amino acids were sensitive to reduced energy intake.

Adult↗

Glucose intolerance after renal transplantation depends upon prednisolone dose and recipient age.

BACKGROUND: Retrospective studies on the prevalence of posttransplant diabetes mellitus (PTDM) in patients on triple-drug immunosuppressive therapy have shown great dispersity, while the incidence of posttransplant impaired glucose tolerance (IGT) is unknown. The aim of our study was to prospectively examine the incidence of posttransplant glucose intolerance and to assess potential risk factors. METHODS: Glucose intolerance was prospectively examined in 173 consecutive kidney transplant recipients by oral glucose tolerance tests (n=167) or the diagnosis of manifest diabetes mellitus (n=6) at 10 weeks after transplant. RESULTS: We found a high incidence of PTDM (18%) and IGT (31%). Univariate analysis revealed that age, family history of diabetes, HLA-B27 phenotype, DR mismatch, rejection, actual prednisolone dose, total methylprednisolone dose, total steroid dose, cytomegalovirus (CMV) infection, and the use of furosemide were associated with PTDM. Age, prednisolone dose, CMV infection, and the use of beta-blockers were associated with IGT. Gender, body mass index, donor source, and cyclosporine level did not influence glucose tolerance. Prednisolone dose, age, family history of diabetes, CMV infection, and HLA-B27 phenotype were independent predictors of PTDM with the use of multiple stepwise logistic regression analysis. Age, prednisolone dose, and the use of a beta-blocker were associated with IGT in the multivariate model. Both univariate and multivariate linear regression analysis revealed a significant relationship between the 2-hr serum glucose and prednisolone dose. The risk of developing PTDM was 5% per 0.01 mg/kg/day of increase in prednisolone dose. CONCLUSIONS: Increased prednisolone dose and older age are strongly associated with the development of posttransplant glucose intolerance.

Adult↗

Haemoglobin is inversely related to plasma lactate and heart rate in the newborn piglet.

It has been hypothesized that an increased level of plasma lactate (La), the product of anaerobic glycolysis, may identify infants with anaemia and early tissue hypoxia. In the newborn piglet, a frequently used model in experimental neonatology, there is a substantial decrease in haemoglobin (Hb) during the first days of life. We have investigated whether a low level of Hb is associated with an increased level of La in the newborn piglet. Arterial blood gas, Hb, glucose, La, and continuous blood pressure and heart rate (HR) recordings were obtained from 66 newborn piglets. In 4 additional piglets recordings were obtained before isovolemic anaemia, during isovolemic anaemia, and after retransfusion of packed red cells. A low concentration of Hb in the newborn piglet correlates with an increased level of La as well as with an increased HR. A reduction of Hb causes an increase in La and in HR. We hypothesize that increased La and increased HR are caused by mild hypoxia due to normal, low Hb levels in the apparently healthy, resting newborn piglet.

Animals↗

Blood gases and hypothermia: some theoretical and practical considerations.

There is much controversy about the optimal bloodgas management of hypothermic patients, whether the hypothermia is caused by accidents or induced before operations. The surgeons and anestesiologists have acquired more clinical experience the last years when operating patients in hypothermia. The comparative physiology has given increased information about the blood gas strategy of heterothermic endotherms and poikilothermic ectotherms during lowering of their core temperature. There are two types of strategies which have been used in clinical medicine the last years in the blood gas management of patients in hypothermia: pH-stat method and alpha-stat method. In the pH-stat method, the arterial carbon dioxide tension (pCO2(a)) is maintained at 5.3 kPa (40 mmHg) and the pH is maintained at 7.40 when measured at the actual temperature. It is then necessary to add CO2 to the inspired gas. In the alpha-method, the arterial carbon dioxide tension and the pH are maintained at 5.3 kPa and 7.40 when measured at +37 degrees C. When a patient is cooled down, the pH-value will increase and the pCO2-value and the pO2-value will decrease with lowering of the temperature if measured at the patients temperature. Both the pH-stat and alpha-stat strategies have theoretical disadvantages. For the optimal myocardial function the alpha-stat method is the method of choice. The pH-stat method may result in loss of autoregulation in the brain (coupling of the cerebral blood flow with the metabolic rate in the brain). By increasing the cerebral blood flow beyond the metabolic requirements, the pH-stat method may lead to cerebral microembolisation and intracranial hypertension. In Norway the alpha-stat strategy is the preferred method.

Animals↗

Autotransfusion after open heart surgery: the oxygen delivery capacity of shed mediastinal blood is maintained.

Autotransfusion of mediastinal shed blood after open heart surgery has become a common and accepted procedure in reducing the need for homologous transfusion during the last 15 years. The objectives of the present study were to investigate the oxygen delivery capacity of autotransfused shed mediastinal blood, compared to patient-blood, during cardiopulmonary bypass and in the postoperative period. Ten consecutive patients undergoing elective cardiac surgery were studied. Mediastinal shed blood was collected in the cardiotomy reservoir and retransfused during the first 18 postoperative hours. The oxygen delivery capacity of the blood to the tissues was calculated by use of the oxygen status algorithm (OSA 2.0) programme and measurement of the 2,3-diphosphoglycerate (2,3-DPG) concentration. Autotransfusion volume ranged from 450-1530 ml per patient (median 824 ml). Shed blood had a mean haemoglobin level of 8.8 g/dl and 7.4 g/dl at 1 h and 6 h of autotransfusion, respectively. There were no significant changes of 2,3-DPG concentration in the patient-blood during cardiopulmonary bypass or after autotransfusion compared to preoperative values. P50 for oxygen (3.6 and 3.6 kPa) and 2,3-DPG concentrations (5.3 and 5.1 mikromol/ml erythrocyte) in shed mediastinal blood (1h and 6h postoperatively) were not significantly different compared to patient-blood. The results demonstrate that the oxygen delivery capacity of shed mediastinal blood is maintained and that the oxygen affinity of patient-blood is not influenced by autotransfusion.

2,3-Diphosphoglycerate↗

Acid-base regulation during hypothermia. a brief review.

Acid-base physiology has mainly focused on mechanisms that maintain normal, extracellular pH at a constant temperature. Usually it is the arterial blood which is considered. As reliable pH meters became generally available in the 1950s it was observed that an arterial pH of about 7.39-7.42 was maintained remarkably constant in normal man and in mammals in general. This moderate degree of blood alkalosis is maintained by chemical buffering, by appropriate adjustment of the lung ventilation and by the kidneys. To measure pH intracellularly was more difficult, but not impossible, and over some time it became apparent that intracellular fluid was close to neutrality. pH values around 6.8 was found. This is a favorable state for retention of metabolites inside the cells. From an analysis by Davis (1) of the ionization constants of several hundred watersoluble biosynthetic intermediates one may argue that the ideal intracellular pH would occur near the neutrality of water where most of these compounds are ionized and thus captured within the cells, with little tendency to escape across the cell membrane. Apparently, if cells are to defend their neutrality and also to eliminate their acid metabolites and CO2, there must be a considerable transmembrane H+ gradient: The hydrogen ion concentration at neutrality is 160 nmol/L (pH 6.8) and that of blood 40 nmol/l (pH 7.4).

Acid-Base Equilibrium↗

[Diagnosis of hemoglobinopathies and thalassemias].

During recents the number of immigrants to Norway from Africa and South East Asia has risen considerably. These persons come from countries with a high prevalence of haemoglobinopathies. Most of the immigrants with haemoglobinopathies are silent carriers, but some have a serious disease or have offspring with serious disease. This situation calls for increasing awareness and knowledge of haemoglobinopathies, especially the thalassemias and sickle cell trait. Genetic counselling is particularly important, since the majority of these immigrants marry within small ethnic groups. This paper gives a survey of the most frequent haemoglobinopathies likely to be encountered in Norway.

Africa↗

Quality specifications for pH and blood gases.

This presentation is built upon experience with use of blood gas results in clinical work during 25 years, experience from the external quality control of 120 blood-gas-analyzers participating in the Norwegian Control Survey 1984-1991, and at last 3 different pH/blood gas inter-analyzer comparisons in Oslo and Bergen in 1980, 1990 and 1992. It is discussed the pure biological variations of the three parameters pH, pCO2 and pO2 as well as the variations in results caused by preanalytical and analytical factors. My proposal for goal of quality for determinations of blood gases (the pure analytical variations, given as EA, Error Allowable) are; pH: 0.02 units on all levels as SD, pCO2: 1-2% (CV) depending on level and the clinical situation. pO2: 2-4% (CV) depending on the level and clinical situation.

Chemistry, Clinical↗

Ionized calcium in human male and female reproductive fluids: relationships to sperm motility.

The levels of ionized calcium in seminal plasma were approximately 20% of the serum levels. In contrast, cervical mucus contained a level of ionized calcium similar to both serum and follicular fluid. Titration of seminal plasma and serum with increasing concentrations of calcium chloride indicated a 10-fold higher calcium-binding capacity for seminal plasma. In a random group of men under semen investigation, concentrations of ionized calcium and citrate in semen were inversely correlated (r = 0.732; P less than 0.001), an observation which was confirmed by studies of split ejaculates. These findings supported the contention that citrate is the major regulator of the levels of ionized calcium in seminal plasma and primarily responsible for maintaining the calcium gradient between the seminal plasma and cervical mucus. No significant relationship could be demonstrated between the levels of ionized calcium in the ejaculates and any of the motility characteristics of the spermatozoa in the same sample. Furthermore, the addition of increasing quantities of calcium chloride (0.16-20.00 mM) to washed spermatozoa had no major effects on their progressive motility. These data suggest that human spermatozoa are effective in maintaining an appropriate level of internal ionized calcium, necessary for normal motility, despite fluctuations in external calcium.

Ascitic Fluid↗

Oxygen uptake and transport in the human organism on the summit of Mt. Everest.

In May 1978 the two Italians, Messner and Habeler, climbed to the summit of Mt. Everest (8848 m above sea level) without use of supplementary oxygen. This must be the extreme limit of what the human organism can do. The upper limit of permanent living for man is considered to be about 5300 m above sea level. The fact that man not only can remain conscious on the summit of Mt. Everest, but climb there without supplementary oxygen is due to a number of changes that take place over a period of hours to months at high altitudes. These changes are termed acclimatization and occur in different systems of the human organism. The gas exchange under these conditions of extreme hypoxia has been studied by many scientific expeditions. Especially the American Medical Research Expedition to Everest in October 1981 lead by Prof. West gave us much better understanding of high altitude physiology. The arterial blood gas values in a man without use of supplementary O2 on the summit have been estimated in average to be pH = 7.76, pCO2 = 1.0 kPa, pO2 = 3.9 kPa. The barometric pressure, alveolar/end capillary pO2 difference, diffusing capacity for O2, alveolar ventilation, cardiac output, p50 and transit time of the erythrocytes in the lungs are among the most important factors to understand how it is possible to climb Everest without supplementary oxygen.

Acclimatization↗

Gastrointestinal absorption and urinary excretion of aluminium in patients with predialysis chronic renal failure.

In a randomized cross-over study, serum and urinary aluminum (A1) was measured in 8 patients with predialysis chronic renal failure. Samples were taken after ingestion of an A1-containing phosphate binder (ACPB) with either water or 7% citric acid, and A1 was analyzed by electrothermal atomic absorption spectrometry. Both serum levels and urinary excretion of A1 increased markedly after ingestion of ACPB with citric acid. Only urinary A1 excretion increased significantly after ACPB with water. Citric acid alone caused no change in serum concentration or urinary excretion of A1. The serum A1 increase after ACPB with citric acid indicates that absorption of A1 is taking place in both upper and lower intestines. Marked individual variations in gastrointestinal A1 absorption, independent of kidney function, were seen after intake of ACPB with citric acid. These variations could not be predicted from changes in serum concentrations or from urinary excretion of A1 after intake of ACPB with water. Intake of ACPB caused a significant decrease in serum phosphate.

Adult↗

Ionized calcium influences gastrin stimulated histamine release and acid secretion, but not histamine stimulated acid output in the totally isolated vascularly perfused rat stomach.

When changing from bovine serum albumin to dextran T70 as colloid without adjusting the total calcium concentration in the vascular perfusate of the totally isolated vascularly perfused rat stomach, we noticed a drastic fall in gastrin-stimulated acid secretion. In the present study the effect of the two colloids on ionized calcium in the vascular perfusate as well as the effect on acid secretion and vascular histamine release were studied. There was no difference in gastrin-stimulated acid secretion or vascular histamine release between the two colloids after adjusting the total calcium concentrations so that ionized calcium was similar. Whereas baseline acid secretion showed no marked dependency of ionized calcium within the range tested (0.73-1.54 mmol l-1, gastrin-stimulated acid secretion was highly dependent on ionized calcium being reduced at the higher concentration of Ca2+. Histamine stimulated acid secretion, on the other hand, was virtually unaffected by the concentration of ionized calcium in the same range. Like gastrin-stimulated acid secretion, gastrin-stimulated histamine release was inhibited at higher Ca2+ concentrations. Thus, elevated Ca2+ concentrations seemed to reduce gastrin-stimulated acid secretion by inhibiting vascular histamine release.

Animals↗

Ionized calcium in plasma during cardiopulmonary bypass.

The composition of the priming fluid in the heart-lung machine is of importance for the homeostasis of the patient during and after cardiopulmonary bypass. We have studied the effect of 5 different priming solutions on the degree of ionization of calcium. The primingsolutions all contained 1700 ml of a basic solution and 800 ml of one of the following solutions: CPD-plasma CPD-plasma added heparine and CaCl2 heparinized plasma 5% albumin in saline 6% dextran 70 in saline. With CPD-plasma in the priming solution, the concentration of ionized calcium dropped to very low values, followed by a normalization during the next 30 minutes, as the citrate disappeared. The addition of CaCl2 to CPD-plasma prevented the abrupt initial drop, but resulted later on in values above the normal range. Heparinized plasma, albumin, and dextran in the priming solution lead to small changes only. Bolus injections of CaCl2 during weaning from bypass resulted in substantial increases in ionized calcium, while the use of CPD-blood products lead to decreases. Citrate has great affinity to calcium ions, making strong complexes. When significant amounts of citrate are used, the level of ionized calcium cannot be predicted, but has to be measured directly. These measurements must be performed frequently.

Adult↗

Measurement of ionized calcium with five types of instruments. An external quality assessment.

An external quality assessment for ionized calcium determinations was carried out in 24 laboratories in Northern Europe. Both protein-free and protein-containing test materials were included in the study. The average within-laboratory variation (CV) for all test materials was 3.1, 1.7, 1.2, 1.8 and 1.3% for the AVL 980 (AVL, Graz, Austria), the Microlyte (Kone, Espoo, Finland), the Nova 2 (Nova Biomedical, Newton, Ma USA), the Orion SS-20 (Orion, Cambridge, Mass., USA), and the ICA1 (Radiometer, Copenhagen, Denmark) respectively. The corresponding interlaboratory CV was 3.1, 2.9, 3.1 and 2.4%. The variation between types of instruments was even larger and caused differences of up to 33%. The results indicate a need for well-defined protein-containing control material.

Calcium↗