Troels Ring | Aarhus University (original) (raw)
Papers by Troels Ring
Files in R to demonstrate quantification of the amount of acid based on electroneutrality
R-code to illustrate methods used in chapter 65 of critical care nephrology
Ugeskrift for Læger, 2012
American journal of therapeutics, Jan 15, 2016
Hyponatremia is associated with increased mortality and is frequently induced by diuretic use. It... more Hyponatremia is associated with increased mortality and is frequently induced by diuretic use. It is uncertain whether diuretic use is linked to mortality risk in patients with hyponatremia. To measure the prognostic impact of diuretic use on 30-day mortality among patients hospitalized with hyponatremia. Using population-based registries, we identified all patients with a serum sodium measurement <135 mmol/L within 24 hours after acute hospital admission in western Denmark from 2006 to 2012 (cumulative population of 2.2 million). We categorized patients as current diuretic users (new and long-term), former users or nonusers, and followed them until death, migration or up to 30 days which ever came first. Thirty-day cumulative mortality and relative risk with 95% confidence interval (CI) controlled for demographics, previous morbidity, renal function, and co-medications. Calculations were also divided by the diuretic type and were repeated after propensity score matching. Thirty-...
Ugeskrift for laeger, Jan 9, 2012
Hyponatraemia with cerebral symptoms is a medical emergency. Prompt management of airway, breathi... more Hyponatraemia with cerebral symptoms is a medical emergency. Prompt management of airway, breathing and circulation together with repeated boluses of 2 ml/kg 3% NaCl constitute a rational treatment. The goal is remission of symptoms. After the initial correction, the main concern is to avoid overcorrection, thus reducing the risk of osmotic demyelination. P-[Na(+)] and diuresis must be measured frequently together with diuresis. Definitive treatment should be directed toward the aetiology.
Thrombosis Research, 1983
The cutaneous bleeding time was shortened after smoking high nicotine cigarettes while not after ... more The cutaneous bleeding time was shortened after smoking high nicotine cigarettes while not after smoking nicotine free cigarettes. The ADP induced primary platelet aggregation was not enhanced. The number of circulating platelet aggregates did not change due to smoking.
Thrombosis Research, 1985
ABST3ACT 1 g acetyl salicylic acid orally significantly enhanced the initial rate of platelet agg... more ABST3ACT 1 g acetyl salicylic acid orally significantly enhanced the initial rate of platelet aggregation induced by 1 pmol/l and 2.5 pm0111 ADD. Sodium salicylate was without effects on the platelet aggregation and specifically it did not prevent acetylsa, licylic acid from inhibiting the secondary aggregation. Sodium salicylate was without effect on the bleeding time and did not inhibit the prolongation. induced by acetyl salicylic acid. Our study do not lend support to the concept of an important interaction in vivo between acetyl salicylic acid and its first metabolite salicylate in man.
Scandinavian Cardiovascular Journal, 1983
Thrombosis of the central veins as a complication of transvenous cardiac pacing fortunately is ra... more Thrombosis of the central veins as a complication of transvenous cardiac pacing fortunately is rare. A case is presented in which symptomatic thrombosis of the subclavian vein arose seven weeks after implantation of a new electrode. The frequency, pathogenesis, clinical picture, complications and treatment of the condition are briefly discussed.
Pediatric Nephrology, 2002
A 16-year-old female had mutations in both alleles of the gene encoding her sodium-chloride cotra... more A 16-year-old female had mutations in both alleles of the gene encoding her sodium-chloride cotransporter; one of these mutations is newly described. Her clinical findings were not typical because of the absence of hypocalciuria in 24-h urine samples, her maximum urine osmolality (U(osm)) was only 802 mosmol/kg H(2)O, and her plasma magnesium (Mg) concentration (P(Mg)) was easily maintained in the normal range with oral Mg supplements for 1 month. In detailed studies, the calcium/creatinine ratio in spot urines with a U(osm) &amp;amp;amp;amp;amp;amp;amp;gt;700 mosmol/kg H(2)O was very low, except during Mg therapy. Renal medullary function did not appear to be compromised because she had a non-urea U(osm)of approximately 600 mosmol/kg H(2)O, reflecting a very high non-urea osmole excretion rate (due to KCl supplements). At age 18 years, her P(Mg) became persistently low despite Mg therapy. We conclude that the clinical criteria for a provisional diagnosis of Gitelman syndrome should be revised. Hypocalciuria may only be evident initially in concentrated spot urine samples. Urine concentrating ability should include an analysis of the non-urea U(osm), especially when patients are taking large KCl supplements.
The Lancet, 1985
May 18, p 1167) are correct in urging vigilance when using sulphasalazine (or any other secondlin... more May 18, p 1167) are correct in urging vigilance when using sulphasalazine (or any other secondline drug) for rheumatoid arthritis, because of the risk ofleucopenia.
The Lancet, 1983
Plasma histamine,l1 serum NCA,12 blood basophils, and FEV in five asthmatics (aged 19-35, mean 29... more Plasma histamine,l1 serum NCA,12 blood basophils, and FEV in five asthmatics (aged 19-35, mean 29 years) who underwent a treadmill exercise task on day 1 and isocapnic hyperventilation with cold air on day 7. After exercise there were significant increases from baseline values in histamine at 5 mm (p<0 05), in NQA at 5 min (p<0 05), and basophils at 5 and at 10 mm (p<0'05). After isocapnic hyperventilation there was a significant increase m plasma histamine at 30 min (p<0-05) but not NCA or basophils. Results as mean±SEM; statistical analysis by Student's t test.
Intensive Care Medicine, 2009
Intensive Care Medicine, 2006
Sir: We read with interest the recent contribution by Bruegger and coworkers in Intensive Care Me... more Sir: We read with interest the recent contribution by Bruegger and coworkers in Intensive Care Medicine [1]. Since both fluid resuscitation and acid-base abnormalities are daily events in the ICU, we agree that the subject is very important. Unfortunately, we find several aspects of the analysis to be rather misleading. First, according to what the authors call “the Stewart model” they observe that the effect of an increasing strong ion difference (SID) and increasing weak plasma acid explains why pH decreases following boluses of 20% albumin. To test this, the authors first calculate A– by the formula: 3.44 × [Prot], citing the study by Constable [2]. Unfortunately, this formula is for Atot, not A–. The correct formula for A– is: A=Atot/(1+10 – pH), Eq. 2 in the same paper [2]. The authors then subtract the change in SID from the (incorrectly calculated) change in A– and compare it to the plasma bicarbonate concentration. The authors then claim that there is “good agreement.” Assuming no change in pCO2, SID and Atot determine the pH and bicarbonate concentrations, and therefore “agreement” is assured. Indeed, the relationship between ∆SID∆A– and ∆bicarbonate is linear, and when pCO2 is 40 mmHg, the equation is: ∆SID∆A– = 0.8862 × ∆bicarbonate. Thus the results obtained by the authors provided no real insight into the acid-base effects of albumin administration. Indeed the serum albumin concentration (before or after) is not even reported. Next the authors infer from their experiment with titrable acidity in 20% albumin that the acidity thus imposed on the patients will likewise explain their findings. We find this argument to be specious. If one uses the same approach to titrate 1 l isotonic sodium chloride from pH 6.68 to 7.4, the amount of acid required is about 1 μmol. Considering that the 16 patients receiving approx. 5 l isotonic sodium chloride sustained a decrease in pH from (presumably) normal values of 7.4 to the mean starting value of 7.28 on being administered approx. 5 μmol “titrable” acid, it seems quite strange to us that giving these same patients later about 6.375 mmol “titrable” acidity (i.e., more than 1000 times more), resulted in only a slight decrease in pH. Indeed the presented experimental data nicely demonstrate that titratable acidity is meaningless in terms of understanding the effect of fluid administration on plasma pH. The data presented cannot be used to assess the value of the physical chemical approach since insufficient data are provided and the calculation of A– is in error. Fortunately, numerous other studies have already addressed this issue in the setting of crystalloid resuscitation [3, 4, 5]. Confirmation in the setting of colloid use would be valuable.
Clinical Rheumatology, 2005
We report the course of a 55-year-old woman, the first patient with primary Sjögren's syndrome an... more We report the course of a 55-year-old woman, the first patient with primary Sjögren's syndrome and distal renal tubular acidosis but without lymphoma to be treated with B-cell depletion using Rituximab. Rapidly after B-cell depletion, remarkable improvement in xerostomia occurred, while serological findings and tubular acidosis have been unchanged. In labial salivary gland biopsy, lymphocyte infiltration and particularly CD20-positive cells decreased strikingly. Aquaporin 1 (AQP-1) expression in myoepithelial cells was very low before treatment and increased noticeably. Apical AQP-5 in acinus cells likewise increased following Rituximab. In contrast, basolateral NKCC1 was expressed at unchanged intensity before and following Rituximab. The improvement has been sustained and still is most gratifying 10 months after treatment. B-cell depletion may be effective treatment in Sjögren's syndrome. Likewise, it may now be possible to separate the immunologic phenomena in Sjögren's syndrome from the consequences of prolonged hyposalivation when studying the pathophysiology of xerostomia.
Experimental physiology, Jan 20, 2016
Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe ... more Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (IP-model). This hyponatraemia model is described as "dilutional" or "syndrome of inappropriate ADH (SIADH)", but seminal studies contradict this interpretation. To confront this issue, we developed an IP-model in a large animal (pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesised that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single IV dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetised and intensively monitored. In vivo brain and muscle water was determined by m...
Have all files in the same directory, say c://mydir - open R, and from the console issue source(&... more Have all files in the same directory, say c://mydir - open R, and from the console issue source("C:/mydir/makeall.r",chdir=TRUE) - 10 figures are made as eps files, results printet in "acid.txt"; install ggplot2 to make the figures
Metabolomics, 2019
In our metabolomics studies we have noticed that repeated NMR acquisition on the same sample can ... more In our metabolomics studies we have noticed that repeated NMR acquisition on the same sample can result in altered metabolite signal intensities. To investigate the reproducibility of repeated NMR acquisition on selected metabolites in serum and plasma from two large human metabolomics studies. Two peak regions for each metabolite were integrated and changes occurring after reacquisition were correlated. Integral changes were generally small, but serum citrate signals decreased significantly in some samples. Several metabolite integrals were not reproducible in some of the repeated spectra. Following established protocols, randomising analysis order and biomarker validation are important.
ACS Omega, 2019
In this study, we show that equilibrium pH can be obtained for any specified fluid with any numbe... more In this study, we show that equilibrium pH can be obtained for any specified fluid with any number of buffers and dissociations. This is done by root finding in the equation for charge balance. We demonstrate that this equation is monotonic in proton concentration for conceivable buffers. We show that the total charge on any buffer is a function of only the total buffer concentration and pH, given the thermodynamic dissociation constants. Using the Davies' equation as a placeholder for single-ion activity coefficients as a function of charge and ionic strength, we develop an iterative algorithm, whereby the apparent dissociation constants are updated from the thermodynamic dissociation constants, and from this, the equilibrium is also identified in the nonideal state. We show how this algebra leads to guaranteed conservation of both thermodynamic dissociation constants and total buffer concentrations because the distribution of buffer species is fixed by the updated dissociation constants, actual pH, and total buffer concentration. Strong ions are assumed to contribute fixed charges. In order to concentrate on the process of modeling the equilibrium pH alone, this algorithm is examined against a series of theoretical results in which the Davies' equation was given the same status. However, a large sample of clinical pH measurements is also examined. To enhance the practical utility, CO 2 and albumin are present as the default condition. We developed "ABCharge", a package in R, an open source language. The main function returns pH, activity coefficients, buffer species distribution, ionic strength, and charge balance for both the ideal and nonideal cases, for any mixture of any buffers with any number of known thermodynamic dissociation constants. Our algorithm can be updated if a more reliable and practical assessment of single-ion activities becomes available. Can Stock Photo/miceking
Nephrology Dialysis Transplantation, 1993
Files in R to demonstrate quantification of the amount of acid based on electroneutrality
R-code to illustrate methods used in chapter 65 of critical care nephrology
Ugeskrift for Læger, 2012
American journal of therapeutics, Jan 15, 2016
Hyponatremia is associated with increased mortality and is frequently induced by diuretic use. It... more Hyponatremia is associated with increased mortality and is frequently induced by diuretic use. It is uncertain whether diuretic use is linked to mortality risk in patients with hyponatremia. To measure the prognostic impact of diuretic use on 30-day mortality among patients hospitalized with hyponatremia. Using population-based registries, we identified all patients with a serum sodium measurement <135 mmol/L within 24 hours after acute hospital admission in western Denmark from 2006 to 2012 (cumulative population of 2.2 million). We categorized patients as current diuretic users (new and long-term), former users or nonusers, and followed them until death, migration or up to 30 days which ever came first. Thirty-day cumulative mortality and relative risk with 95% confidence interval (CI) controlled for demographics, previous morbidity, renal function, and co-medications. Calculations were also divided by the diuretic type and were repeated after propensity score matching. Thirty-...
Ugeskrift for laeger, Jan 9, 2012
Hyponatraemia with cerebral symptoms is a medical emergency. Prompt management of airway, breathi... more Hyponatraemia with cerebral symptoms is a medical emergency. Prompt management of airway, breathing and circulation together with repeated boluses of 2 ml/kg 3% NaCl constitute a rational treatment. The goal is remission of symptoms. After the initial correction, the main concern is to avoid overcorrection, thus reducing the risk of osmotic demyelination. P-[Na(+)] and diuresis must be measured frequently together with diuresis. Definitive treatment should be directed toward the aetiology.
Thrombosis Research, 1983
The cutaneous bleeding time was shortened after smoking high nicotine cigarettes while not after ... more The cutaneous bleeding time was shortened after smoking high nicotine cigarettes while not after smoking nicotine free cigarettes. The ADP induced primary platelet aggregation was not enhanced. The number of circulating platelet aggregates did not change due to smoking.
Thrombosis Research, 1985
ABST3ACT 1 g acetyl salicylic acid orally significantly enhanced the initial rate of platelet agg... more ABST3ACT 1 g acetyl salicylic acid orally significantly enhanced the initial rate of platelet aggregation induced by 1 pmol/l and 2.5 pm0111 ADD. Sodium salicylate was without effects on the platelet aggregation and specifically it did not prevent acetylsa, licylic acid from inhibiting the secondary aggregation. Sodium salicylate was without effect on the bleeding time and did not inhibit the prolongation. induced by acetyl salicylic acid. Our study do not lend support to the concept of an important interaction in vivo between acetyl salicylic acid and its first metabolite salicylate in man.
Scandinavian Cardiovascular Journal, 1983
Thrombosis of the central veins as a complication of transvenous cardiac pacing fortunately is ra... more Thrombosis of the central veins as a complication of transvenous cardiac pacing fortunately is rare. A case is presented in which symptomatic thrombosis of the subclavian vein arose seven weeks after implantation of a new electrode. The frequency, pathogenesis, clinical picture, complications and treatment of the condition are briefly discussed.
Pediatric Nephrology, 2002
A 16-year-old female had mutations in both alleles of the gene encoding her sodium-chloride cotra... more A 16-year-old female had mutations in both alleles of the gene encoding her sodium-chloride cotransporter; one of these mutations is newly described. Her clinical findings were not typical because of the absence of hypocalciuria in 24-h urine samples, her maximum urine osmolality (U(osm)) was only 802 mosmol/kg H(2)O, and her plasma magnesium (Mg) concentration (P(Mg)) was easily maintained in the normal range with oral Mg supplements for 1 month. In detailed studies, the calcium/creatinine ratio in spot urines with a U(osm) &amp;amp;amp;amp;amp;amp;amp;gt;700 mosmol/kg H(2)O was very low, except during Mg therapy. Renal medullary function did not appear to be compromised because she had a non-urea U(osm)of approximately 600 mosmol/kg H(2)O, reflecting a very high non-urea osmole excretion rate (due to KCl supplements). At age 18 years, her P(Mg) became persistently low despite Mg therapy. We conclude that the clinical criteria for a provisional diagnosis of Gitelman syndrome should be revised. Hypocalciuria may only be evident initially in concentrated spot urine samples. Urine concentrating ability should include an analysis of the non-urea U(osm), especially when patients are taking large KCl supplements.
The Lancet, 1985
May 18, p 1167) are correct in urging vigilance when using sulphasalazine (or any other secondlin... more May 18, p 1167) are correct in urging vigilance when using sulphasalazine (or any other secondline drug) for rheumatoid arthritis, because of the risk ofleucopenia.
The Lancet, 1983
Plasma histamine,l1 serum NCA,12 blood basophils, and FEV in five asthmatics (aged 19-35, mean 29... more Plasma histamine,l1 serum NCA,12 blood basophils, and FEV in five asthmatics (aged 19-35, mean 29 years) who underwent a treadmill exercise task on day 1 and isocapnic hyperventilation with cold air on day 7. After exercise there were significant increases from baseline values in histamine at 5 mm (p<0 05), in NQA at 5 min (p<0 05), and basophils at 5 and at 10 mm (p<0'05). After isocapnic hyperventilation there was a significant increase m plasma histamine at 30 min (p<0-05) but not NCA or basophils. Results as mean±SEM; statistical analysis by Student's t test.
Intensive Care Medicine, 2009
Intensive Care Medicine, 2006
Sir: We read with interest the recent contribution by Bruegger and coworkers in Intensive Care Me... more Sir: We read with interest the recent contribution by Bruegger and coworkers in Intensive Care Medicine [1]. Since both fluid resuscitation and acid-base abnormalities are daily events in the ICU, we agree that the subject is very important. Unfortunately, we find several aspects of the analysis to be rather misleading. First, according to what the authors call “the Stewart model” they observe that the effect of an increasing strong ion difference (SID) and increasing weak plasma acid explains why pH decreases following boluses of 20% albumin. To test this, the authors first calculate A– by the formula: 3.44 × [Prot], citing the study by Constable [2]. Unfortunately, this formula is for Atot, not A–. The correct formula for A– is: A=Atot/(1+10 – pH), Eq. 2 in the same paper [2]. The authors then subtract the change in SID from the (incorrectly calculated) change in A– and compare it to the plasma bicarbonate concentration. The authors then claim that there is “good agreement.” Assuming no change in pCO2, SID and Atot determine the pH and bicarbonate concentrations, and therefore “agreement” is assured. Indeed, the relationship between ∆SID∆A– and ∆bicarbonate is linear, and when pCO2 is 40 mmHg, the equation is: ∆SID∆A– = 0.8862 × ∆bicarbonate. Thus the results obtained by the authors provided no real insight into the acid-base effects of albumin administration. Indeed the serum albumin concentration (before or after) is not even reported. Next the authors infer from their experiment with titrable acidity in 20% albumin that the acidity thus imposed on the patients will likewise explain their findings. We find this argument to be specious. If one uses the same approach to titrate 1 l isotonic sodium chloride from pH 6.68 to 7.4, the amount of acid required is about 1 μmol. Considering that the 16 patients receiving approx. 5 l isotonic sodium chloride sustained a decrease in pH from (presumably) normal values of 7.4 to the mean starting value of 7.28 on being administered approx. 5 μmol “titrable” acid, it seems quite strange to us that giving these same patients later about 6.375 mmol “titrable” acidity (i.e., more than 1000 times more), resulted in only a slight decrease in pH. Indeed the presented experimental data nicely demonstrate that titratable acidity is meaningless in terms of understanding the effect of fluid administration on plasma pH. The data presented cannot be used to assess the value of the physical chemical approach since insufficient data are provided and the calculation of A– is in error. Fortunately, numerous other studies have already addressed this issue in the setting of crystalloid resuscitation [3, 4, 5]. Confirmation in the setting of colloid use would be valuable.
Clinical Rheumatology, 2005
We report the course of a 55-year-old woman, the first patient with primary Sjögren's syndrome an... more We report the course of a 55-year-old woman, the first patient with primary Sjögren's syndrome and distal renal tubular acidosis but without lymphoma to be treated with B-cell depletion using Rituximab. Rapidly after B-cell depletion, remarkable improvement in xerostomia occurred, while serological findings and tubular acidosis have been unchanged. In labial salivary gland biopsy, lymphocyte infiltration and particularly CD20-positive cells decreased strikingly. Aquaporin 1 (AQP-1) expression in myoepithelial cells was very low before treatment and increased noticeably. Apical AQP-5 in acinus cells likewise increased following Rituximab. In contrast, basolateral NKCC1 was expressed at unchanged intensity before and following Rituximab. The improvement has been sustained and still is most gratifying 10 months after treatment. B-cell depletion may be effective treatment in Sjögren's syndrome. Likewise, it may now be possible to separate the immunologic phenomena in Sjögren's syndrome from the consequences of prolonged hyposalivation when studying the pathophysiology of xerostomia.
Experimental physiology, Jan 20, 2016
Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe ... more Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (IP-model). This hyponatraemia model is described as "dilutional" or "syndrome of inappropriate ADH (SIADH)", but seminal studies contradict this interpretation. To confront this issue, we developed an IP-model in a large animal (pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesised that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single IV dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetised and intensively monitored. In vivo brain and muscle water was determined by m...
Have all files in the same directory, say c://mydir - open R, and from the console issue source(&... more Have all files in the same directory, say c://mydir - open R, and from the console issue source("C:/mydir/makeall.r",chdir=TRUE) - 10 figures are made as eps files, results printet in "acid.txt"; install ggplot2 to make the figures
Metabolomics, 2019
In our metabolomics studies we have noticed that repeated NMR acquisition on the same sample can ... more In our metabolomics studies we have noticed that repeated NMR acquisition on the same sample can result in altered metabolite signal intensities. To investigate the reproducibility of repeated NMR acquisition on selected metabolites in serum and plasma from two large human metabolomics studies. Two peak regions for each metabolite were integrated and changes occurring after reacquisition were correlated. Integral changes were generally small, but serum citrate signals decreased significantly in some samples. Several metabolite integrals were not reproducible in some of the repeated spectra. Following established protocols, randomising analysis order and biomarker validation are important.
ACS Omega, 2019
In this study, we show that equilibrium pH can be obtained for any specified fluid with any numbe... more In this study, we show that equilibrium pH can be obtained for any specified fluid with any number of buffers and dissociations. This is done by root finding in the equation for charge balance. We demonstrate that this equation is monotonic in proton concentration for conceivable buffers. We show that the total charge on any buffer is a function of only the total buffer concentration and pH, given the thermodynamic dissociation constants. Using the Davies' equation as a placeholder for single-ion activity coefficients as a function of charge and ionic strength, we develop an iterative algorithm, whereby the apparent dissociation constants are updated from the thermodynamic dissociation constants, and from this, the equilibrium is also identified in the nonideal state. We show how this algebra leads to guaranteed conservation of both thermodynamic dissociation constants and total buffer concentrations because the distribution of buffer species is fixed by the updated dissociation constants, actual pH, and total buffer concentration. Strong ions are assumed to contribute fixed charges. In order to concentrate on the process of modeling the equilibrium pH alone, this algorithm is examined against a series of theoretical results in which the Davies' equation was given the same status. However, a large sample of clinical pH measurements is also examined. To enhance the practical utility, CO 2 and albumin are present as the default condition. We developed "ABCharge", a package in R, an open source language. The main function returns pH, activity coefficients, buffer species distribution, ionic strength, and charge balance for both the ideal and nonideal cases, for any mixture of any buffers with any number of known thermodynamic dissociation constants. Our algorithm can be updated if a more reliable and practical assessment of single-ion activities becomes available. Can Stock Photo/miceking
Nephrology Dialysis Transplantation, 1993