Analysis of polymorphonuclear leukocyte respiratory burst activity in uremic patients using whole-blood chemiluminescence

The respiratory burst activity of peripheral leukocytes from 17 patients with chronic renal failure and 12 healthy individuals was assessed using the technique of whole-blood chemiluminescence (CL). Luminol- and lucigenin-dependent CL was measured in two dilutions of venous blood following stimulation with serum-treated zymosan or phorbol myristate acetate, and the CL peaks associated with a polymorphonuclear leukocyte count of 10(4)/ml were calculated. The mean CL peaks for the patients were significantly higher than those for the controls in all experimental designs (p less than 0.05). This enhanced leukocyte respiratory burst activity was not associated with the underlying renal abnormality or with the type of dialysis treatment, but may have been related to the induction of tissue enzymes which is known to occur in uremia.     

Serum erythropoietin and erythropoiesis in primary and secondary hyperparathyroidism: effect of parathyroidectomy.

Primary as well as secondary hyperparathyroidism may be associated with anemia, and parathyroidectomy (PTx) may improve or even heal it. The precise link between the two conditions is still matter of discussion. The purpose of the present study was to investigate possible effects of PTx on serum immunoreactive erythropoietin (iEPO) in secondary (group I, n = 23), and primary (group II, n = 16) hyperparathyroidism patients, and in 3 patients undergoing cervicotomy for thyroid mass removal (group III). In group I patients, circulating iEPO levels rose from 23.1 +/- 4.8 mU/ml before PTx to 28.2 +/- 5.0 and 245 +/- 125 mU/ml (mean +/- SEM) at day 7 (p = NS) and 14 after PTx (p less than 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 +/- 13,317 to 86,533 +/- 13,462/mm3 (p less than 0.05, n = 23). In 4 of these patients serum iEPO levels could be measured again 12-24 months after PTx. They were slightly higher than those determined before PTx: 37.0 +/- 8.4 versus 31.8 +/- 13.5 mU/ml. Their hematocrits were also higher than before PTx: 12.8 +/- 0.9 versus 11.0 +/- 0.9 g/dl. In group II patients, serum iEPO levels remained unchanged after PTx: 17.5 +/- 2.0 mU/ml before PTx and 20.0 +/- 3.0 mU/ml 14 days PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 +/- 3,000 to 40,827 +/- 4,080/mm3 (p less than 0.01). In group III patients, serum iEPO, reticulocyte count, and hemoglobin remained stable after surgery. Since all group I patients had received vitamin D supplementation after PTx, we studied an additional group of 14 chronic dialysis patients (group IV) who received either calcitriol (1 micrograms/day, n = 7) or placebo (n = 7) during 14 days. The patients on calcitriol treatment, but not those on placebo, had a significant decrease of serum iEPO: 18.6 +/- 4.9 versus 16.0 +/- 4.2 mU/ml (p less than 0.03). In conclusion, PTx led to a striking increase of serum iEPO and blood reticulocytes in uremic patients with secondary hyperparathyroidism, and an increase of reticulocyte count, but not of iEPO, in patients with primary hyperparathyroidism. Marked changes of circulating PTH, extra-or intracellular calcium and phosphorus concentrations as well as of tissue sensitivity to EPO after PTx could all be responsible. In contrast, the surgical procedure and the therapeutic increase in plasma calcitriol do not appear to be involved.     

Single-dose Pharmacokinetics of Recombinant Human Erythropoietin in Patients with Various Degrees of Renal Failure

The pharmacokinetic profile of recombinant human erythropoietin(rHuEpo) was studied after a single intravenous dose of 150U/kg in ten patients with various degrees of renal function:group I, creatinine clearance >80 ml/min, n=2; group II,creatinine clearance 10–50 ml/min, n=6; group III, creatinineclearance <3 ml/min (patients undergoing haemodialysis) n=2.Erythropoietin concentrations in serum and urine samples obtainedover 48 h were measured by RIA. rHuEpo was cleared from circulationin an exponential fashion, the half-life ranged from 6.5 to12.7 h (mean 9.03 h) and was not different between the groups.The apparent volume of distribution varied from 0.041 to 0.0991/kg(mean 0.0701/kg) this corresponds to 1.5 times the plasma volumeand was unrelated to kidney function. Renal clearance (groupsI, II) accounted for less than 3% of total body clearance, bothparameters were unaffected by decreasing renal function. These results indicate that, in accordance with animal data,the elimination of rHuEpo occurs mainly through non-renal mechanisms.     

Adjuvant chemotherapy for osteosarcoma: a randomized prospective trial

To determine the role of chemotherapy in the multidisciplinary treatment of patients with osteosarcoma, a randomized prospective trial of postoperative adjuvant chemotherapy was begun in 1981. Fifty-nine patients with nonmetastatic classic intramedullary osteosarcoma were randomized; 32 received postoperative adjuvant chemotherapy consisting of high-dose methotrexate, Adriamycin (Adria Laboratories, Columbus, OH), and BCD (bleomycin, cytoxan, actinomycin D), and 27 patients received no adjuvant chemotherapy. At a median follow-up of 2 years, there was a statistically significant improvement in both disease-free and overall survival in those who received adjuvant chemotherapy. In addition, there was no difference in the less than 20% disease-free or overall survival of patients treated in the 1970s who did not receive chemotherapy, as compared with the concurrent nontreatment controls. Therefore, with identical staging procedures, uniform surgical management, and standard pathologic evaluation, postoperative adjuvant chemotherapy definitely improves disease-free and overall survival in patients with osteosarcoma.     

Characterization of an antibody raised against reduced glycoprotein IIIa of human platelets.

A polyclonal antibody against reduced and vinylpyridylethylated human glycoprotein IIIa was raised in rabbits. Its reactivity with reduced GPIIIa was about 500 times higher than that of the antibody against native GPIIIa. The lowest amounts of purified reduced and native GPIIIa recognized by the antibody against reduced GPIIIa were 25 and 400 ng, respectively. The antibody did not recognize native GPIIIa (about 1-2 micrograms) in platelet extracts and chymotryptic degradation products of GPIIIa. It inhibited ADP-induced platelet aggregation but it did not inhibit fibrinogen binding to ADP-stimulated platelets. Our experiments suggest that the antigenicity of GPIIIa (beta 3 integrin) depends on the conformation of the molecule determined by numerous S-S bridges between cysteine residues.     

Dissociation of the acute effects of alcohol on implicit and explicit memory processes

The effects of alcohol (0, 0.3 and 0.6 g/kg) on learning and memory were assessed in independent groups of male student volunteers. Subjects were shown a list of words and asked to form an image of a scene involving each word 1 hr after drinking an alcohol-containing beverage. Alcohol consumption impaired the ability of subjects to explicitly remember the words in a test of free recall. However, no impairment was observed if memory for the same material was assessed implicitly using a backwards-reading or word-completion task. That is, both alcohol-and placebo-treated subjects showed similar degrees of priming. The data indicate that alcohol's effects on memory are selective.     

Serial immunoreactive erythropoietin levels in autologous blood donors

The variations in plasma erythropoietin (EPO) concentration during preoperative deposit of autologous blood were studied in 12 patients (8 men, 4 women). Four donations were scheduled at weekly intervals. A predonation hemoglobin concentration of 11 g per dL (110 g/L) was required. Hemoglobin concentration decreased from 14.3 +/- 1.1 g per dL (143 +/- 11 g/L) (mean +/- SD) before the first donation to 11.7 +/- 0.7 g per dL (117 +/- 7 g/L) on Day 22 (p less than or equal to 0.0001). Reticulocyte counts increased from a median of 31,800 (range, 4900-95,000) per microL (median, 32 x 10(9)/L [range, 5-95 x 10(9)/L]) to 93,800 (16,800-194,900) per microL (median, 94 x 10(9)/L [range, 17-195 x 10(9)/L]) on Day 28 (p less than or equal to 0.01). Plasma EPO concentration was 17.8 +/- 5.1 mU per mL prior to the first donation and displayed a small and transient peak after each donation. A sustained elevation followed each peak. Although plasma EPO concentration differed significantly from the baseline value after the first donation, only the peak concentrations after the second (35.5 +/- 15.5 mU/mL), third (38.0 +/- 14.5 mU/mL), and fourth (36.1 +/- 11.0 mU/mL) donations exceeded the normal range. The moderate, biphasic increase in plasma EPO concentration and the moderate increase in erythropoiesis suggest two strategies in autologous blood donation that should be investigated with respect to efficiency and safety: 1) more aggressive donation schemes, which reduce donation intervals and/or the minimum hemoglobin concentration and 2) the administration of recombinant human EPO.     

Plasma cortisol levels before and during "low-dose" hydrocortisone therapy and their relationship to hemodynamic improvement in patients with septic shock

OBJECTIVES: To compare cortisol levels during "low-dose" hydrocortisone therapy to basal and ACTH-stimulated endogenous levels and to assess whether clinical course and the need for catecholamines depend on cortisol levels and/or pretreatment adrenocortical responsiveness. DESIGN AND SETTING: Prospective observational study in a medical ICU of a university hospital. PATIENTS: Twenty consecutive patients with septic shock and a cardiac index of 3.5 l/min or higher, started on "low-dose" hydrocortisone therapy (100 mg bolus, 10 mg/h for 7 days and subsequent tapering) within 72 h of the onset of shock. MEASUREMENTS AND RESULTS: Basal total and free plasma cortisol levels ranged from 203 to 2169 and from 17 to 372 nmol/l. In 11 patients cortisol production was considered "inadequate" because there was neither a response to ACTH of at least 200 nmol/l nor a baseline level of at least 1000 nmol/l. Following the initiation of hydrocortisone therapy total and free cortisol levels increased 4.2- and 8.5-fold to median levels of 3,587 (interquartile range 2,679-5,220) and 1,210 (interquartile range 750-1,846) nmol/l on day 1, and thereafter declined to median levels of 1,310 nmol/l and 345 nmol/l on day 7. Patients with "inadequate" steroid production could be weaned from vasopressor therapy significantly faster, although their plasma free cortisol concentrations during the hydrocortisone treatment period did not differ. CONCLUSIONS: (a) During proposed regimens of "low-dose" hydrocortisone therapy, initially achieved plasma cortisol concentrations considerably exceed basal and ACTH stimulated levels. (b) Cortisol concentrations decline subsequently, despite continuous application of a constant dose. (c) "Inadequate" endogenous steroid production appears to sensitize patients to the hemodynamic effects of a "therapeutic rise" in plasma cortisol levels.