Accumulation of the neutrophil-derived protein YKL-40 during storage of various blood components.

OBJECTIVE AND DESIGN: Post transfusion infectious complications associated with allogeneic blood components may depend on storage time and may be related to extracellular accumulation of bioactive substances during storage. YKL-40 is a glycoprotein located in the specific granules of the neutrophils. While exocytosed it may play a role in inflammation and remodelling of the extracellular matrix. We studied the potential accumulation of YKL-40 in blood components during storage. METHODS: Using a RIA method extracellular accumulation of YKL-40 was determined in supernatants from whole blood, plasma-reduced whole blood, buffy-coat-depleted SAGM (saline-adenine-glucose-mannitol) blood, whole blood leukocyte depleted by prestorage filtration, and whole blood leukocyte depleted by bedside filtration. The blood was donated by volunteer, healthy blood donors, and stored under standard blood bank conditions for 35 days. RESULTS: Extracellular accumulation of YKL-40 increased significantly in a time-dependent manner during storage for 35 days of non-filtered whole blood, plasma-reduced whole blood, and SAGM blood, respectively. Prestorage leukocyte depletion of whole blood prevented extracellular YKL-40 accumulation, while YKL-40 accumulation was not reduced by bedside leukocyte depletion. CONCLUSION: YKL-40 appears to accumulate extracellularly in a time-dependent manner in standard erythrocyte components. Prestorage leukocyte depletion by filtration of whole blood may be an effective procedure to prevent extracellular YKL-40 accumulation during storage of erythrocyte components.

Serum YKL-40 and colorectal cancer.

YKL-40 is a mammalian member of the chitinase protein family. Although the function of YKL-40 is unknown, the pattern of its expression suggests a function in remodelling or degradation of extracellular matrix. High serum YKL-40 has been found in patients with recurrent breast cancer and has been related to short survival. In the present study we analysed YKL-40 in preoperative sera from patients with colorectal cancer and evaluated its relation to survival. Serum YKL-40 was determined by RIA in 603 patients. Survival after operation was registered, and median follow-up time was 61 months. Three hundred and forty patients died. Sixteen per cent of the patients with Dukes' A, 26% with Dukes' B, 19% with Dukes' C and 39% with Dukes' D had high serum YKL-40 levels (adjusted for age). Analysis of serum YKL-40 as a continuous variable showed an association between increased serum YKL-40 and short survival (P < 0.0001). Patients with high preoperative serum YKL-40 concentration had significantly shorter survival than patients with normal YKL-40 (HR = 1.7; 95% CI: 1.3-2.1, P < 0.0001). Multivariate Cox analysis including serum YKL-40, serum CEA, Dukes' stage, age and gender showed that high YKL-40 was an independent prognostic variable for short survival (HR = 1.4; 95% CI: 1.1-1.8, P = 0.007). These results suggest that YKL-40 may play an important role in tumour invasion.

Efficacy of recombinant human erythropoietin administered subcutaneously to CAPD patients once weekly.

OBJECTIVE: The purpose of the present study was to compare the dosage requirements of recombinant human erythropoletin (rHuEPO) administered subcutaneously (SC) either one or three times weekly. DESIGN: A randomized, prospective study. SETTING: The patients were recruited from two university hospitals and five county hospitals. PATIENTS: Thirty-three anemic patients on continuous ambulatory peritoneal dialysis (CAPD) treatment for end-stage renal failure completed the study. INTERVENTIONS: Initially, all were treated with rHuEPO SC three times a week until hemoglobin blood levels (Hb) remained constant between 105 and 121 g/L for three months. Following randomization, 17 patients continued the same treatment schedule (group A), while 16 patients received the same dose, but administered only once weekly for three months (group B). MAIN OUTCOME MEASURES: The Hb levels and rHuEPO doses at the start and at the end of the three-month study period. RESULTS: In group A the median Hb at randomization was 118 g/L (109-119) (25-75 percentiles) and, after three months, was 113 g/L (106-119) (p = 0.13), while in group B the median Hb was 114 g/L (108-119) and 114 g/L (106-120), respectively (p = 0.50). In group A the weekly dose of rHuEPO remained virtually unchanged during the study period, 65 (55-86) and 66.3 (55-95) U/kg/week, respectively, while in group B it was increased from 60.2 (46-88) to 77 (60-90) U/kg/week. The 22% increase (p = 0.03) took place during the last two weeks. CONCLUSIONS: Our findings indicate that a once-weekly SC dosing regimen of rHuEPO in anemic CAPD patients was equally effective in maintaining a stable hemoglobin level as a thrice-weekly dosing regimen.

Serum YKL-40: a new potential marker of prognosis and location of metastases of patients with recurrent breast cancer.

YKL-40 is a recently discovered glycoprotein which is related in amino acid sequence to the chitinase protein family, but has no chitinase activity. Although the function of YKL-40 is presently unknown, the pattern of its expression by some tissues suggests that YKL-40 could function in tissue remodelling. The diagnostic features and relation to survival of serum YKL-40 have not been examined previously in human malignancies. In the present study YKL-40 was measured in serum obtained from 60 patients at the time that breast cancer recurrence was suspected. The median serum YKL-40 in patients with visceral or bone metastases was 328 and 157 micrograms/l, respectively and significantly higher compared to controls (99 micrograms/l, P < 0.001). Kaplan-Meier survival curves demonstrated that survival rates after 18 months were 24% for patients with high serum YKL-40 (> 207 micrograms/l = the 95 percentile of controls) and 60% for patients with normal serum YKL-40. The significance of the difference between the shorter survival of patients with high serum YKL-40 and the longer survival of patients with normal serum YKL-40 was high (P < 0.0009). When evaluated with other prognostic factors of survival after recurrence of breast cancer, serum YKL-40 and serum lactate dehydrogenase (LDH) were the most significant independent factors. The results indicate that determination of serum YKL-40 can be used as a prognostic marker related to the extent of disease and survival of patients with recurrence of breast cancer. In addition, the serum YKL-40 level may be of value in the follow-up of patients with breast cancer and in evaluating potential metastatic spread.

[Giant fecaloma]. / Gigantisk faekalom.

A case of a giant faecaloma of the sigmoid colon secondary to surgery is reported. The predisposing factors, the diagnostic and therapeutic approaches are discussed.

Nephrogenic ascites. Case report and review of the literature.

Nephrogenic ascites is a clinical diagnosis defined as persistent ascites in an uremic patient without evidence for a causative (specific) underlying disease. The incidence is not known. Contributing mechanisms may include peritoneal membrane changes, fluid overload, hyperparathyroidism, reduced lymphatic drainage, heart failure and hypoproteinemia. Rigid fluid control, intensive hemodialysis, high-protein diet, intravenous albumin infusion, intraperitoneal steroid injections and paracenteses as well as implantation of a peritoneatrial pump have all been found ineffective as treatment. Peritoneal dialysis has been shown to resolve ascites, however, the only effective treatment is so far renal transplantation. The development of nephrogenic ascites is associated with a poor prognosis. Thus, one year after the development of nephrogenic ascites 1/3 had died.

Pharmacokinetics of 1 alpha-hydroxycholecalciferol after intraperitoneal, intravenous and oral administration in patients undergoing peritoneal dialysis.

Intravenous (i.v.) injection of vitamin D3 has a well known suppressive effect on the release of parathyroid hormone. However, the i.v. route is inconvenient in patients undergoing peritoneal dialysis. Moreover, no study has been published on the pharmacokinetics of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) after intraperitoneal (IP), i.v. and oral administration. Therefore, the appearance of 1,25-(OH)2D3 after administration of 1 alpha-OHD3 was studied in 8 peritoneal dialysis patients. Open, prospective, randomized cross-over design with single doses of 1 alpha-OHD3 (80 ng/kg BW) given on 3 separate occasions either IP, i.v. or oral was applied. After the administration of 1 alpha-OHD3, blood was collected at baseline and 0.5, 1, 2, 3, 4, 6, 12 and 24 h for measurement of circulating 1,25-(OH)2D3. A one compartment model with first order absorption and elimination (Cpl = Be-ke*t-Ae-ka*t) was fitted to the concentrations following i.v. administration. Following IP and oral administration the concentrations did not reach maximum levels within the time of blood sampling. In all cases, the 24 h area under the time/concentration curve for 1,25-(OH)2D3 (AUC24) was calculated using the trapezoidal method. Residual areas were calculated using the terminal slope from i.v. administration, and added to AUC24 giving AUC0-->infinity. After i.v. administration A, ka, B, ke, t1/2, AUC24 and AUC0-->infinity were (mean +/- SD) 62.9 +/- 16.4 pg/ml, 0.76 +/- 0.30 h-1, 71.6 +/- 14.7 pg/ml, 0.017 +/- 0.015 h-1, 109.4 +/- 129.5 h, 1315.8 +/- 236.9 pg/ml x h and 10322.2 +/- 11473.7 pg/ml x h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Tertiary hyperparathyroidism treated by ultrasonically guided percutaneous fine-needle ethanol injection.

Advanced renal failure is often accompanied by secondary and tertiary hyperparathyroidism. In tertiary hyperparathyroidism it is necessary to reduce the gland mass. The present study describes the response to treatment with percutanous injection of ethanol of enlarged parathyroid nodules in 9 uremic patients. All had hypercalcemia, severely elevated serum levels of parathyroid hormone and ultrasonically detectable enlarged parathyroid glands. Three patients did not respond to the treatment. In the remaining 6 patients, serum values of total and ionized calcium were normalized and the serum values of parathyroid hormone were reduced at least 30% after 18 months. Seven of the patients experienced an improvement of symptoms. No complications were seen. We conclude that treatment with ethanol injection can be used as an alternative to conventional parathyroidectomy to improve parathyroid status in selected patients.

Acute effect of oral, intraperitoneal, and intravenous 1 alpha-hydroxycholecalciferol on markers of bone metabolism.

OBJECTIVE: To study the acute effect of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) on serum levels of alkaline phosphatase, Ca2+, osteocalcin, parathyroid hormone (PTH), phosphate and type I and III procollagens (PICP and PIIINP respectively) in patients undergoing peritoneal dialysis. Also, 1,25-(OH)2D3 was measured. DESIGN: Single doses of 1 alpha-OHD3 (80 ng/kg body wt) were given in randomized cross-over fashion, orally, intraperitoneally (i.p.) and intravenously (i.v.) on three occasions. Blood was sampled at 0, 1, 6, 12, and 24 h after administration of 1 alpha-OHD3. MAIN RESULTS: Following oral administration of 1 alpha-OHD3, a decrease in serum alkaline phosphatase was seen when levels at 1 and 6 h were compared to baseline (P < 0.05). Oral and i.v. drug administrations resulted in an increasing trend in serum Ca2+ throughout the study (P < 0.05). Moreover, a difference in serum Ca2+ was found when 24-h levels after oral 1 alpha-OHD3 dose was compared to baseline (P < 0.05). Serum osteocalcin at 12 and 24 h after oral 1 alpha-OHD3 compared to baseline were increased (P < 0.05). Intact PTH followed a circadian rhythm after all three routes of drug delivery. After 24 h, significant decreases of intact PTH were observed in the oral and i.v. group. No changes in serum phosphate and serum PICP levels were observed over time after oral, i.p., and i.v. delivery of 1 alpha-OHD3. However, serum PIIINP following oral and i.p. administration of 1 alpha-OHD3 decreased at 1 and 6 h (P < 0.05). CONCLUSION: Oral and i.v. administration of 1 alpha-OHD3 does influence serum levels of osteocalcin, PTH, and PIIINP: Noticeable is the significant increase in serum osteocalcin after oral administration of 1 alpha-OHD3, the remarkable increase (22.6%) in osteocalcin 24 h after i.v. 1 alpha-OHD3, though not statistically significant, the increase in serum PTH levels 12 h following oral and i.v. doses of 1 alpha-OHD3 and the moderate effect on serum Ca2+ levels.

Influence of oral magnesium supplementation on cardiac events among survivors of an acute myocardial infarction.

OBJECTIVE: To investigate the effect of long term oral magnesium treatment on incidence of cardiac events among survivors of an acute myocardial infarction. DESIGN: Double blind, placebo controlled parallel study in which patients were randomised to treatment or placebo. SETTING: Two coronary care units and corresponding outpatient clinics. SUBJECTS: 468 survivors of an acute myocardial infarction (289 men and 178 women) aged 31-92. INTERVENTIONS: One tablet of 15 mmol magnesium hydroxide or placebo daily for one year. MAIN OUTCOME MEASURES: Incidences of reinfarction, sudden death, and coronary artery bypass grafting in one year. RESULTS: There was no significant difference between treatment and placebo groups in the incidence of each of the three cardiac events, but when the events were combined and drop outs were excluded from calculations there was a significantly higher incidence of events in the treatment group (56/167 v 33/153; relative risk 1.55 (95% confidence interval 1.07 to 2.25); p = 0.02). When the timing of events was incorporated by means of a Kaplan-Meier plot the treatment group showed a significantly higher incidence of events whether drop outs were included or excluded (p < 0.025). CONCLUSION: Long term oral treatment with 15 mmol magnesium daily doses not reduce the incidence of cardiac events in survivors of an acute myocardial infarction and, indeed, seems to increase the risk of developing a cardiac event. Consequently, this treatment cannot be recommended as secondary prophylaxis for such patients.

[Nephrogenic ascites]. / Nefrogen ascites.

Nephrogenic ascites is a clinical diagnosis defined as persistent ascites in a uraemic patient without evidence of a causative specific underlying disease. Contributing mechanisms may include peritoneal membrane changes, fluid overload, hyperparathyroidism, reduced lymphatic drainage, heart failure and hypoproteinemia. A specific treatment has not yet been found. Rigid fluid control, intensive haemodialysis, high-protein diet, intravenous albumin infusion, intraperitoneal steroid injections and paracenteses as well as implantation of a peritoneoatrial pump were all found to be ineffective. Use of peritoneal dialysis has been shown to resolve ascites, but the only effective treatment is renal transplantation, as demonstrated in the case-report.

[Acute uremia after renal cholesterol embolism]. / Akut uraemi efter renale kolesterolembolier.

A case of acute uraemia caused by cholesterol emboli in the kidneys in a sixty-six year old male with arteriosclerosis is presented. No effective treatment is available, but recognizing the condition may save the patient from otherwise time-consuming extensive diagnostic programmes.

[Alcoholic ketoacidosis]. / Alkoholisk ketoacidose.

Alcoholic ketoacidosis is seen in chronic alcoholics who have been starving for days. This was the case in the present patient who had metabolic acidosis on admission. The differential diagnoses are primarily diabetic ketoacidosis, intoxication (salicylate, methanol, ethylene glycol and fenformin), lactate acidosis, hunger-induced ketoacidosis and uraemia. Treatment should consist of intravenous glucose and correction of the dehydration with isotonic sodium chloride.

1 alpha-Hydroxycholecalciferol adsorption to peritoneal dialysis bags: influence of time, glucose concentration, temperature, and albumin.

The present study examines the adsorptive phenomenon of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) to peritoneal dialysis bags. One minute after injection of 1 alpha-OHD3 into the dialysis bags, a significant adsorption to the bags was observed in experiments where albumin was not added. A higher temperature (37 degrees versus 23 degrees C) in bags containing 13.6 mg glucose/ml resulted in less adsorption (P < 0.05). Adding albumin to bags at 37 degrees C with a glucose concentration of 13.6 mg/ml, reduced the adsorptive phenomenon significantly (P < 0.01). Bags tested at 37 degrees C with a glucose concentration of 38.6 mg/ml resulted in a significantly higher 1 alpha-OHD3 adsorption than bags containing 13.6 mg glucose/ml (P < 0.01). It is concluded that adsorption of 1 alpha-OHD3 to dialysis bags is affected by time, albumin, temperature and glucose concentrations. Substantial amounts of 1 alpha-OHD3 is retained by the peritoneal dialysis system when albumin is not added.

The effect of intravenous magnesium therapy on serum and urine levels of potassium, calcium, and sodium in patients with ischemic heart disease, with and without acute myocardial infarction.

Serum concentrations of magnesium, potassium, calcium, and sodium were determined on admission of 224 patients to the hospital and after 2, 4, and 6 days in hospital; all were admitted to the hospital with suspected acute myocardial infarction (AMI). On admission, the patients were randomly allocated to 48 hours of treatment with magnesium intravenously or placebo. One hundred twenty-three patients had AMI (of whom 53 [43%] were treated with magnesium) and 101 had their suspected AMI disproven (of whom 51 [50%] were treated with magnesium). In a supplementary study, serum and urine levels of magnesium, potassium, calcium, and sodium, together with serum levels of parathyroid hormone, were determined before and after intravenous magnesium treatment in six patients with AMI and six patients with ischemic heart disease but without AMI. In both studies, magnesium therapy was associated with significant alterations in extracellular ion homeostasis. Serum concentrations of potassium decreased during the initial days of hospitalization in the patients treated with placebo, but increased slightly in the patients treated with magnesium infusions. These increments in the serum concentrations of magnesium and potassium correlated significantly. The increase in the serum concentration of potassium after magnesium infusions was due to a reduced renal potassium excretion level (from 71.3 to 49.4 mmol/24 h), indicating the existence of a divalent-monovalent cation exchange mechanism in the nephron. This hypothesis was supported by the observation that renal sodium excretion likewise decreased after magnesium infusions (from 83.2 to 59.2 mmol/24 h). Serum concentration of calcium decreased significantly after magnesium treatment (from 2.35 mmol/L on admission to 2.15 mmol/L after 24 hours in the hospital) in the AMI group, in contrast to the placebo-treated patients, where no significant fluctuations in serum concentration of calcium were detected during the initial six days. This decrease in serum concentration of calcium was due to a marked increase in renal calcium excretion (from 3.43 mmol/24 h before to 6.59 mmol/24 h after magnesium infusion). A correlation between increments in serum magnesium concentration and decrements in serum calcium concentration was detected. No change in serum levels of parathyroid hormone was found before and after magnesium infusions. Both serum and urine levels of magnesium significantly increased after magnesium treatment to levels above the upper normal limits (serum magnesium concentration increased from 0.81 to 1.21 mmol/L, urine magnesium excretion levels from 3.57 to 16.57 mmol/24 h for both serum and urine changes.(ABSTRACT TRUNCATED AT 400 WORDS)

Myocardial contractility and performance capacity after magnesium infusions in young healthy persons: a double-blind, placebo-controlled, cross-over study.

To evaluate the effect of intravenous magnesium (Mg) treatment on the inotropic state of the heart and maximal work capacity, 9 healthy volunteers were entered in a double-blind, placebo-controlled, cross-over study. Separated by an interval of three weeks, the volunteers were tested twice, each time randomly allocated to receive either an intravenous injection of 10 mmol magnesium chloride dissolved in 100 ml isotonic sodium chloride or placebo of isotonic sodium chloride only. Before and after each infusion myocardial inotropism was evaluated by echocardiography. Mitral-septal distance (MSA) was used as a measure for ejection fraction. On each test day an ergometer bicycle exercise test was performed, and maximal work capacity was calculated. Magnesium treatment reduced the MSA (from 4.2 to 2.9 mm, p = 0.07), while no difference was found after placebo treatment. Likewise, a tendency toward increasing fractional shortening after magnesium treatment was detected, although this difference was not statistically significant (p = 0.1). No difference in maximal work capacity between the magnesium and placebo periods was found. Serum magnesium concentrations and placebo periods was found. Serum magnesium concentrations rose significantly after the infusions (from 0.82 to 1.38 mmol/l, p less than 0.001). It is concluded that intravenous magnesium does not exert a negative inotropic effect on the myocardium as previously stated. On the contrary, we found a tendency toward a positive inotropic effect. However, the observed differences are of borderline statistical significance and a more extended study, employing invasive measurements of cardiac inotropism appears to be necessary.

One-year death rate in 270 patients with suspected acute myocardial infarction, initially treated with intravenous magnesium or placebo.

In a double-blind, placebo-controlled study, 273 patients with suspected acute myocardial infarction (AMI) were randomized to receive either 48-h magnesium (Mg) or placebo therapy intravenously, initiated immediately on admission to hospital. We describe the results from a 1-year survey in 270 of the patients, who were available for follow-up. Patients were equally divided: 135 received Mg and 135 received placebo. Mg treatment was associated with a marked reduction in 1-year death rate from 32% in the placebo group to 20% in the Mg group (p = 0.018). If only death from ischemic heart disease is considered, the figures were 28% in the placebo group as opposed to 15% in the Mg group (p = 0.006). This reduction was mainly due to a reduction in mortality during the initial 30 days after inclusion in the study (17% vs. 7%), after which the difference in mortality between the two groups did not reach statistical significance (18% vs. 15%, p = 0.56). The beneficial effect of Mg on mortality was partly linked to a reduced incidence of arrhythmias (27% vs. 16%), and partly to a reduced incidence of infarction (63% vs. 48%) during the initial hospitalization. However, factors unknown to us were also involved, as revealed by a remaining statistically significant partial regression coefficient, when sex, age, cardiovascular history, development of AMI, and development of arrhythmias were considered. It is concluded that intravenous Mg treatment is beneficial to patients with acute ischemic heart disease and should be adopted as part of the routine treatment of these patients.