Elastase inhibitors of sputum sol phase: variability, relationship to neutrophil elastase inhibition, and effect of corticosteroid treatment.

The concentrations of three known elastase inhibitors (alpha 1 proteinase inhibitor, antileucoprotease, and alpha 2 macroglobulin) have been determined in the sputum of six patients with obstructive bronchitis over five consecutive days. Antileucoprotease was the major inhibitor measured and potentially could provide more than 80% of the elastase inhibition, whereas the contribution of alpha 2 macroglobulin was less than 0.2%. Comparison with the inhibitory capacity of the secretions active against human neutrophil elastase showed that the inhibitors could account for only about half of the inhibition measured. This suggests the presence of a substantial amount of unrecognised inhibitor. Corticosteroid treatment in 10 patients reduced the mean alpha 1 proteinase inhibitor concentration (p less than 0.025) from 18.6 micrograms/ml (SD 22.5) to 9.8 (6.6). Antileucoprotease, however, increased (p less than 0.05) from 20.5 micrograms/ml (24.3) to 39.3 (23.4). These changes were associated with an increase in elastase inhibition (p less than 0.025) from 180 (160) micrograms elastase/ml secretion to 310 (130), suggesting a beneficial effect of steroid treatment on the antielastases in lung secretions.     

Inhibitory capacity of alpha 1 antitrypsin in lung secretions: variability and the effect of drugs.

The inhibitory function of alpha 1 antitrypsin (alpha 1AT) has been studied in the lung secretions of 31 patients with chronic obstructive bronchitis. The inhibitory capacity for a single sample showed a wide range (median 0.13 micrograms porcine pancreatic elastase (PPE) inhibited per microgram alpha 1 antitrypsin; range 0-0.55 micrograms), and all but five of 86 samples studied were capable of inhibiting some porcine pancreatic elastase. No sample showed free elastase activity, however. The inhibitory capacity, studied in six patients over five consecutive days, varied daily within the same individual (coefficient of variation 9.0-108.9%). Corticosteroid treatment (40 mg prednisone daily) increased the inhibitory capacity of sputum alpha 1 antitrypsin in 10 patients (2p less than 0.05) from a median value of 0.13 micrograms PPE inhibited per microgram alpha 1AT (range 0.06-0.36) before treatment to 0.22 micrograms PPE inhibited per microgram alpha 1AT (range 0.09-0.65) after treatment. The inhibitory capacity of sputum was higher than in the corresponding bronchoalveolar lavage sample from the same patient (2p less than 0.05; n = 10). The median value for sputum was 0.22 micrograms PPE inhibited per microgram alpha 1AT (range 0-0.55) and the value for lavage fluid was 0.07 micrograms PPE inhibited per microgram alpha 1AT (range 0-0.27).     

Diffusion of cefmenoxime into prostatic fluid in the patients with acute bacterial prostatitis

Expressed prostatic fluid (EPS) levels and serum levels of cefmenoxime (CMX) after intravenous administration were examined in 16 patients with acute bacterial prostatitis and 23 patients without prostatic diseases. Blood was drawn at 30, 60, 120 minutes and EPS was taken by prostatic massage at 60 minutes after the intravenous administration of 2 g CMX to evaluate the concentration of CMX. The concentration of CMX was determined by the bioassay using the E. coli NIHJ JC strain. The relationships between the EPS/serum ratio and peripheral WBC counts, CRP value and ESR 1h value were also analyzed. The serum levels of CMX at 60 minutes ranged between 20.3 micrograms/ml and 73.5 micrograms/ml (mean +/- S.D.: 41.8 +/- 14.2 micrograms/ml) in 16 patients with acute prostatitis, and between 21.5 micrograms/ml and 89.5 micrograms/ml (mean +/- S.D.: 49.5 +/- 18.7 micrograms/ml) in 23 patients without prostatic diseases. The EPS levels ranged between 0.4 micrograms/ml and 30.8 micrograms/ml (mean +/- S.D.: 12.6 +/- 9.6 micrograms/ml) in 16 patients with acute prostatitis, and between 0 and 2.3 micrograms/ml (mean +/- S.D.: 0.7 +/- 0.8 microgram/ml) in 19 patients without prostatic diseases. In 4 patients without prostatic diseases, the EPS amount was not large enough to evaluate the concentration of CMX. The EPS/serum ratio ranged between 0.006 and 0.697 (mean +/- S.D.: 0.31 +/- 0.21) in patients with acute prostatitis and between 0 and 0.058 (mean +/- S.D.: 0.015 +/- 0.018) in patients without prostatic diseases. The diffusion of CMX into the prostatic fluid in patients with acute prostatitis was strikingly higher than that in patients without prostatic diseases (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of cigarette smoking, pulmonary inflammation, and lung disease on concentrations of carcinoembryonic antigen in serum and secretions.

A specific radioimmunoassay for carcinoembryonic antigen was used to investigate aspects of its measurement in lung disease. The results confirm that serum carcinoembryonic antigen concentrations are higher in healthy smokers and patients with chronic obstructive bronchitis than in healthy non smokers (p less than 0.01). Corticosteroid treatment reduced the concentration in nine patients with bronchitis (p less than 0.05). Other inflammatory lung diseases (bronchiectasis, pneumonia, fibrosing alveolitis) are not associated with a raised serum carcinoembryonic antigen concentration. The sputum concentrations were about 100 times those found in serum and there was a positive correlation (r = 0.611 2p less than 0.01) between the concentrations in sputum and serum in patients with bronchitis. No preferential rise in sputum concentration was found in current smokers or patients with lung carcinoma (n = 16). A higher ratio of carcinoembryonic antigen to albumin concentration (p less than 0.05) was, however, found in lavage fluid obtained from the tumour site than in fluid from "normal" lung in the same patients, suggesting an increase in carcinoembryonic antigen secretion in the vicinity of the tumour. Despite this "local" effect the sputum concentration does not, however, appear to be a useful marker of lung carcinoma and the measurement could not be used as a screening test.     

Sinus bradycardia in obstructive jaundice--correlation with total serum bile acid concentrations

Obstructive jaundice is often listed among the causes of sinus bradycardia. The latter is usually attributed to the effect of bile salts on the sino-atrial node. The purpose of this study was to determine the frequency of sinus bradycardia (heart rate less than 50/min) in 50 patients with severe or moderate cholestasis, and to relate sinus rate and intracardiac conduction to total serum conjugated bile acid concentrations. The latter were measured using a solid-phase 125I radio-immunoassay. The mean sinus rate (+/- SD) in the patients was 74.1 +/- 11.6/min (range 47-100/min). One patient had a sinus rate of less than 50/min and 2 had rates of 50-60/min. The mean total serum conjugated bile acid concentration was 251.1 +/- 198.8 mumol/l (range 13-1000 mumol/l). There was no correlation in individual patients between total serum bile acid concentration and sinus rate (r = +0.097), P-R interval (r = +0.210) or corrected Q-T interval (r = -0.085). We conclude that sinus bradycardia is not a feature of obstructive jaundice and that high serum bile acid concentrations do not exert a slowing effect on the sino-atrial node.     

Low serum iron concentration in acute cholecystitis. A discriminator of severity of infection

This study demonstrates that serum iron levels are significantly depressed during acute cholecystitis. Mean admission serum iron concentration for 18 patients who had required emergency cholecystectomy within 48 hours of hospitalization was 40.9 micrograms/100 ml +/- 27.08 (7.32 mumol/l) while for 108 patients who had undergone elective cholecystectomy in the same 18-month period the mean concentration was 90.5 micrograms/100 ml +/- 34.27 (16.2 mumol/l); a mean difference of 49.6 micrograms/100 ml (3.92 mumol/l) (t = 5.8395, P less than 0.00001). Mean serum iron level in seven patients with culture positive acute cholecystitis was 26.4 micrograms/100 ml +/- 10.45 (4.73 mumol/l), significantly different (P less than 0.05) than in 11 patients with culture negative cholecystitis, 50.3 micrograms/100 ml +/- 30.41 (9.00 mumol/l). Admission serum iron level averaged 25.6 micrograms/100 ml (4.58 mumol/l) in three patients with gangrenous gallbladders and was 18 micrograms/100 ml (3.22 mumol/l) in one patient with empyema of the gallbladder. Determination of serum iron level may help distinguish patients with significant infections requiring urgent surgery from patients with biliary colic.     

Aluminum concentrations in serum, dialysate, urine and bone among patients undergoing continuous ambulatory peritoneal dialysis (CAPD)

Aluminum (Al) concentration in serum, urine, and dialysate was estimated in 21 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In 12 of the patients bone Al concentration was measured as well. Mean serum Al level was 32.4 +/- 21.0 micrograms/l. The Al concentrations in the dialysate and urine were 9.1 +/- 4.1 micrograms/l and 52.5 +/- 47.3 micrograms/l, respectively. Bone Al concentration was 21.0 +/- 14.9 ppm and correlated significantly with concentrations of Al in serum (p less than 0.01) and dialysate (p less than 0.01). A mass transfer (MT) from the patients to the dialysate was observed in all patients (-44.0 +/- 28.8 micrograms/24 h). There was a highly significant correlation between peritoneal Al MT and serum Al (p less than 0.001), actual Al consumption (p less than 0.05) and bone Al concentration (p less than 0.005) supporting the existence of an overflow phenomenon. Despite very low Al levels in the dialysate, patients are at risk of elevated Al levels in the serum, dialysate, urine and bone because of consumption of Al-containing phosphate binders.     

Calcium alginate, an aluminum-free phosphate binder, in patients on CAPD

Since dialysis solutions in CAPD are now nearly aluminum free, the only source for elevated aluminum levels are aluminum-containing phosphate binders. Elimination with CAPD is insufficient to prevent aluminum accumulation. Therefore, we investigated a phosphate binder consisting of calcium alginate, a natural polyuronic acid, containing 100 mg calcium/g substance in 14 patients on CAPD over a period of one year. The patients had previously been treated with aluminum-containing phosphate binders for a period of 24.3 +/- 21.3 months. During a period of 3 weeks before changing to the new phosphate binder the mean (+/- SD) serum phosphorus concentration was 1.8 +/- 0.4 mmol/l, while at the end of one year of treatment with calcium alginate the concentration was 1.6 +/- 0.4 mmol/l. In order to lower serum phosphorus to this level, it was necessary to increase the mean (+/- SD) amount of calcium alginate from 6.9 +/- 1.3 g per day at the beginning of the study to 8.3 +/- 2.1 g per day at the end. The mean (+/- SD) serum calcium concentration did not change throughout the study period. Serum levels of alkaline phosphatase, 1.25 (OH)2 vitamin D3, and intact parathyroid hormone did not change as well. The mean (+/- SD) serum aluminum level declined from 36.0 +/- 20 to 14.0 +/- 11.3 micrograms/l after 6 months (p less than 0.001). In conclusion, calcium alginate is a good alternative to aluminum-containing phosphate binders and to phosphate binders on a calcium base as it does not lead to hypercalcemia. It prevents aluminum intoxication and has no serious side effects.     

Elastolytic activity of alveolar macrophages in chronic bronchitis: comparison of current and former smokers

We have compared the macrophage elastolytic activity of a group of current and former smokers with irreversible airflow obstruction. Elastolytic activity was determined in an initial bronchoalveolar lavage cell population and in alveolar macrophages cultured for three days, to investigate whether enhanced macrophage elastolytic activity alone is a determining factor in the susceptibility of some smokers to obstructive lung disease. Twenty current smokers and 12 former smokers who had abstained from smoking for at least three years were studied. All patients had spirometric evidence of irreversible air flow obstruction. Current smokers had a cell yield (mean +/- SD) of 138.7 +/- 36.4 X 10(6) cells (alveolar macrophages 94.2% +/- 2.1%) compared with 31.4 +/- 14.1 X 10(6) cells (macrophages 86.5% +/- 4.7%) in former smokers. Elastolytic activity in the initial lavage cell population from current and former smokers, measured with the synthetic elastase substrate succinyl-L-alanyl-L alanyl-L-alanine-p-nitroanilide, and expressed as the equivalent of 1 microgram of porcine pancreatic elastase, was respectively 0.113 +/- 0.003 and 0.096 +/- 0.004 microgram pancreatic elastase/mg cell protein. After three days in culture macrophage elastolytic activity in the current and former smokers' cells was respectively 0.107 +/- 0.006 and 0.011 +/- 0.001 microgram pancreatic elastase/mg cell protein (p less than 0.05). The elastase activity of the cultured alveolar macrophages from five current smokers had the inhibitor profile of a metalloproteinase. Our results indicate that enhanced macrophage elastolytic activity alone is not a determining factor in the susceptibility of some smokers to develop obstructive lung disease.     

Ranitidine bioavailability and disposition kinetics in patients undergoing chronic hemodialysis

The absorption and disposition of single-dose intravenous (i.v.) and oral ranitidine were evaluated in 6 patients undergoing chronic hemodialysis. Ranitidine was given as either 50 mg (0.16 mM) i.v. or 150 mg (0.48 mM) tablets 4 h prior to hemodialysis according to a randomized cross-over design with tests separated by 2 weeks. Following i.v. administration, the peak serum ranitidine concentration was 761 +/- 207 micrograms/l (mean +/- SD) and the observed peak after the oral dose was 833 +/- 206 micrograms/l at 3.5 +/- 1.2 h. To convert micrograms/l to microM/l, divide by 314. The terminal elimination rate constants for the i.v. and oral doses were 0.062 +/- 0.013 and 0.058 +/- 0.004 h-1, respectively, with an apparent volume of distribution of 139.6 +/- 35.3 liters and total body clearance 8.5 +/- 1.6 liters/h for the i.v. dose. Hemodialysis clearances during the i.v. and oral studies were 3.2 +/- 0.9 and 3.1 +/- 1.0 liters/h, respectively, and the mean amount removed by hemodialysis following i.v. administration was 3.9 +/- 2.7 mg. The bioavailability of ranitidine was 54.3 +/- 13.5%. Based on these single-dose data, a daily oral dose of 150 mg ranitidine in patients with end-stage renal disease should provide a mean ranitidine serum concentration of approximately 350 micrograms/l with less than 10% of body stores of ranitidine being lost during any dialysis session.     

Hyperaluminemia in renal failure: the influence of age and citrate intake

Following the occurrence of aluminum encephalopathy in four patients with chronic renal failure, we studied 34 azotemic patients seen during the same year and five volunteers who took varying combinations of aluminum hydroxide and an alkalinizing citrate (Shohl's) solution. We found that the four encephalopathic cases were older than the 34 azotemic patients (68 years +/- 14 SD, vs 50 +/- 13, p less than 0.05), had a higher mean serum aluminum value (727 micrograms/l +/- 320 vs 92 +/- 73, p less than 0.005), had taken more aluminum hydroxide (5 g/day +/- 0.9 vs 1.6 +/- 1.8, p less than 0.01), and more Shohl's solution (64 ml/day +/- 19 vs 20 +/- 29, p less than 0.01). In all 38 patients the serum aluminum values correlated directly with age (p = 0.01), aluminum hydroxide (p = 0.001) and concomitant citrate intake (p = 0.004). In the five healthy volunteers the 24-hour urinary aluminum excretion increased from a baseline of 22 micrograms +/- 19 SD to 167 +/- 109 (p = 0.05) during aluminum hydroxide intake, rising to 580 +/- 267 (p = 0.01) during the simultaneous intake of citrate and aluminum hydroxide. Corresponding serum aluminum values were 11 micrograms/l +/- 2 SD, 44 +/- 34 (p = 0.1), and 98 +/- 58 (p less than 0.05). Thus citrate seems to enhance aluminum absorption and may cause encephalopathy in patients with chronic renal failure, especially the elderly.     

Nutritional anaemia in 11-year-old schoolchildren in the western Cape

A nutritional anaemia survey was carried out on 610 11-year-old coloured, black and white schoolchildren in urban and rural communities in the western Cape. The mean (+/- 1 SD) haemoglobin concentration was 13.0 +/- 1.2 g/dl. The coloured and black subgroups considered together had a significantly lower mean haemoglobin concentration than the white subgroup (12.8 +/- 1.2 g/dl v. 13.4 +/- 1.0 g/dl) (F = 37.47; P less than 0.0001). The urban population as a whole had a significantly lower geometric mean (1 SD range) serum ferritin concentration than the rural population (25.6 (13.5-48.6) micrograms/l v. 34.1 (21.3-54.6) micrograms/l) (F = 42.94; P less than 0.0001). The lowest geometric mean serum ferritin values were found in the urban coloured (23.1 (11.5-46.4) micrograms/l) and urban black schoolchildren (23.7 (13.2-42.6) micrograms/l), with figures of less than 12 micrograms/l in 11.7% and 12.5% respectively. Although 28% of the children had red cell folate values below the recommended lower limit of normal (175 ng/ml), probability plot analysis of the data suggested that folate deficiency was not a major problem in the study population. The calculated daily iron and folate intakes were below the age-related recommended dietary allowance (RDA) in all the subgroups, yet anaemia was relatively uncommon. These findings suggest that the RDA values are too high. Overall the prevalence of nutritional anaemia was low and only the urban coloured subgroup showed significant second populations with low haemoglobin and serum ferritin measurements.     

Study on the concentration of cefminox sodium in serum and prostatic tissue]

The concentration of cefminox sodium (CMNX) in serum and prostatic tissue was determined in 25 patients with benign prostatic hypertrophy. One gram of CMNX was intravenously administered prior to transurethral prostatectomy. Blood and prostatic tissue were obtained 1 hour after the administration of CMNX. The concentration of CMNX was 69.17 +/- 17.47 micrograms/ml (mean +/- SD) in serum and 5.33 +/- 2.33 micrograms/g (mean +/- SD) in the prostatic tissue. The ratio of the prostatic tissue concentration/serum concentration was 8.18 +/- 4.45% (mean +/- SD). There was no correlation between serum and prostatic tissue level of CMNX.     

Pulmonary hypertension and polymorphonuclear leukocyte elastase after esophageal cancer operations

To evaluate the role of polymorphonuclear leukocyte (PMN) elastase in pulmonary impairment occurring after operation for esophageal cancer, 10 patients were randomized preoperatively into two equal groups. One group received a placebo infusion and the other, an infusion of the PMN elastase inhibitor ulinastatin. In the placebo group, the mean plasma PMN elastase level increased from 154 +/- 23 micrograms/L preoperatively to 449 +/- 56 micrograms/L at 6 hours postoperatively (p less than 0.01), whereas the mean plasma fibronectin concentration decreased from 490 +/- 70 micrograms/mL preoperatively to 265 +/- 81 micrograms/L on postoperative day 2 (p less than 0.01). The mean pulmonary vascular resistance increased markedly from 151 +/- 24 dynes.s.cm-5.m-2 preoperatively to 284 +/- 76 dynes.s.cm-5.m-2 at 6 hours postoperatively (p less than 0.01). In the group given ulinastatin, 150,000 units every 12 hours from the start of the operation, the mean PMN elastase value at 6 hours postoperatively was lower (275 +/- 66 micrograms/L; p less than 0.01) and the fibronectin level on postoperative days 1 and 2, higher (p less than 0.05). A lower pulmonary vascular resistance was noted into day 2 (p less than 0.05). Our results suggest that PMN elastase may participate in the development of postoperative pulmonary impairment.     

Increase of body iron stores estimated by the increase of serum ferritin concentration during a treatment of 200 mg Fe++ daily after gastrointestinal surgery

A 6-week iron therapy of 200 mg Fe++ daily was given to 13 men and 12 women who had previously undergone various kinds of common gastrointestinal surgery and who had empty iron stores estimated from low serum ferritin concentration. The results were compared with those of a control group corresponding to the study group in respect of sex, number of patients, primary disease, previous operation, empty iron stores (serum ferritin), blood hemoglobin, serum iron, sedimentation rate, blood leukocytes, serum transferrin, folate and vitamin B12. The iron therapy restored the lack of body iron, for the serum ferritin concentrations increased from 12 +/- 7 to 30 +/- 11 micrograms/l (p less than 0.001) in the men and from 10 +/- 6 to 30 +/- 12 micrograms/l (p less than 0.001) in the women, whereas the corresponding changes in the control group were from 10 +/- 9 to 11 +/- 8 micrograms/l and from 11 +/- 8 to 13 +/- 11 micrograms/l in the men and women, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum Tamm-Horsfall glycoprotein level in children with various renal diseases.

Serum Tamm-Horsfall glycoprotein (THGP) concentrations were measured by a competitive enzyme-linked immunosorbent assay using peroxidase-labeled THGP in 168 patients, aged 10.5 +/- 4.6 years, with various renal diseases. Using this method, THGP was determined in the concentration range of 10-10(3) micrograms/l. Serum THGP levels ranged from 130 to 350 micrograms/l in 32 control subjects, aged 1-16 years with normal renal function. In most patients with renal disease, the serum THGP levels were lower than those in control subjects. In particular, the serum THGP levels were more reduced according to the decrease in the clearance values of endogenous creatinine (CCR). These findings suggested that the measurement of serum THGP levels is helpful in the evaluation of renal function. On the other hand, 3 patients with vesicoureteric reflux showed higher serum THGP levels than control subjects, though the CCR values in 1 of these patients was lower. These high serum THGP levels may be the result of urinary backflow into circulation.     

Elevated serum elastase and alpha-1-antitrypsin levels in hemolytic uremic syndrome

Clinical observations and experimental studies have pointed to a role for leukocytes in the pathogenesis of the typical or epidemic form of the hemolytic uremic syndrome. As a result of these observations we measured serum elastase levels and the levels of two protease inhibitors, alpha-1-antitrypsin and alpha-2-macroglobulin in 12 patients with this syndrome. The serum elastase levels were significantly elevated in patients compared with normal individuals (421 +/- 278 vs 91 +/- 27 mg/dl, p less than 0.005) and patients with renal diseases not caused by hemolytic uremic syndrome (191 +/- 254 mg/dl, p less than 0.025). The serum alpha-1-antitrypsin levels were also significantly elevated: hemolytic uremic syndrome vs normals (774 +/- 260 vs 285 +/- 98 ng/ml, p less than 0.0001); and in hemolytic syndrome compared with patients with renal diseases not caused by hemolytic uremic syndrome (774 +/- 260 vs 335 +/- 131 ng/ml, p less than 0.0001). There were no significant differences in the alpha-2-macroglobulin levels among the three groups. There was a significant correlation between the serum elastase levels and the total white cell counts as well as between the elastase and the polymorphonuclear cell counts but not among any of these values and the serum creatinine concentrations. These results provide additional evidence favoring the possibility that leukocytes are activated in patients with hemolytic uremic syndrome.     

Decreased free 1,25-dihydroxycholecalciferol index in patients with the nephrotic syndrome

The serum concentrations of calcium, phosphorus, parathyroid hormone, vitamin D3 metabolites and their transport protein (DBP) were measured in 18 patients with the nephrotic syndrome (mean daily proteinuria 8.8 g). The glomerular filtration rate was normal in 13 patients while the remaining 5 had a mild degree of renal failure. The serum concentrations of total protein, albumin and DBP were significantly decreased in patients with the nephrotic syndrome. The serum calcium concentration was decreased but the calculated ionized calcium concentration remained normal. The serum concentrations of 25-hydroxycholecalciferol (5.3 +/- 3.1 micrograms/l) and 1,25-dihydroxycholecalciferol [1,25-(OH)2D3 (20 +/- 12 ng/l)] were significantly lower in patients with the nephrotic syndrome and normal glomerular filtration rates than in normal controls (14.4 +/- 4 micrograms/l and 42 +/- 13 ng/l, respectively). The free 1,25-(OH)2D3 index was also significantly below normal (0.9 +/- 0.4 vs. 1.8 +/- 0.4). Total and free 1,25-(OH)2D3 were still further reduced in patients with mild renal failure. The nephrotic syndrome thus results in mild vitamin D depletion with decreased free 1,25-(OH)2D3 concentrations but generally without secondary hyperparathyroidism.     

Effect of demeclocycline on renal function and urinary prostaglandin E2 and kallikrein in hyponatremic cirrhotics

8 cirrhotics with hyponatremia were given demeclocycline (DMC) 900 mg/day to investigate its effect on renal function, plasma renin activity, aldosterone and urinary excretion of prostaglandin E2 and kallikrein. In 7 patients DMC induced an increase of free water clearance (from -0.36 +/- 0.06 to 0.13 +/- 0.06 ml/min) and serum sodium concentration (from 125.4 +/- 0.09 to 131.1 +/- 1.0 mEq/l, mmol/l). In 5 of these patients DMC also induced a marked reduction of glomerular filtration rate (from 72.2 +/- 6.2 to 31,2 +/- 4.7 ml/min) and renal plasma flow (from 468 +/- 98 to 195 +/- 55 ml/min) which could not be explained on the basis of hypovolemia. In each case this renal impairment was not associated with changes in urinary concentration of beta 2-microglobulin, urinary casts excretion, fresh urine sediment or urine protein content and disappeared after discontinuation of the drug. DMC induced a marked increase in the urinary excretion of prostaglandin E2 (from 0.82 +/- 0.27 to 6.16 +/- 1.91 ng/min) in 6 out of the 7 patients who responded to DMC and a marked reduction in urinary kallikrein (from 16.1 +/- 4.4 to 4.2 +/- 1.6 pkat/min) in the 5 patients who developed renal insufficiency. The serum DMC concentration was greater than 5 micrograms/ml in all patients who responded to DMC, greater than 8 micrograms/ml in all cases who developed renal insufficiency and of 3 micrograms/ml in the case not responding to DMC. (ABSTRACT TRUNCATED AT 250 WORDS)     

Concentrations of thyroxine-binding globulin in sera and peritoneal dialysates in patients on chronic peritoneal ambulatory dialysis

Losses in thyroxine-binding globulin (TBG) in peritoneal dialysate and thyroid function were evaluated in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), in comparison to patients on hemodialysis (HD) without TBG loss in the dialysate. The TBG concentration in the peritoneal dialysate was 0.26 +/- 0.09 microgram/ml (mean +/- SD, n = 24), with a daily loss of 2.47 +/- 0.94 mg. The serum TBG level in CAPD patients was 21.0 +/- 4.71 micrograms/ml (n = 24), which was not significantly different from that in HD patients (20.0 +/- 5.72 micrograms/ml, n = 24) or in healthy Japanese subjects. The serum TBG level correlated positively with the TBG loss and TBG level in the peritoneal dialysate (p less than 0.001). The serum T4 level in CAPD patients (4.93 +/- 1.38 microgram/dl, n = 24) was significantly greater than in HD patients (4.08 +/- 1.30 microgram/dl, n = 24, p less than 0.05).