Application of an erythrocyte aluminum assay in the diagnosis of aluminum-associated microcytic anemia in patients undergoing dialysis and response to deferoxamine therapy

A method for measuring erythrocyte aluminum content was developed. Erythrocyte aluminum levels correlated with plasma aluminum concentrations in normal controls and in patients undergoing dialysis (r = 0.90, p less than 0.001). In vitro studies showed that erythrocyte aluminum concentrations were not altered by contamination of blood samples, which is a common problem with plasma determinations. The need for anticoagulation and rapid processing were disadvantages of this assay. In the dialysis population studied, the correlative data between mean cell volume and both plasma and erythrocyte aluminum levels (r = -0.50, p less than 0.001; and r = -0.69, p less than 0.001) and lack of correlation with serum ferritin suggested that aluminum overload and not iron deficiency was the cause of microcytic anemia. Patients undergoing continuous ambulatory peritoneal dialysis had lower plasma and erythrocyte aluminum levels and absence of microcytic anemia compared with patients undergoing hemodialysis. Therapy with deferoxamine in 13 patients with aluminum-related microcytic anemia resulted in a decrease in erythrocyte and plasma aluminum content in all patients (265.5 +/- 69.2 micrograms/L to 22.6 +/- 9.7 micrograms/L and 196 +/- 30 micrograms/L to 129 +/- 13.8 micrograms/L). The relatively smaller decrease in plasma aluminum levels suggested mobilization of aluminum from tissues other than erythrocytes. Aluminum chelation most probably occurred from premature erythrocytes, because in vitro studies showed that deferoxamine was unable to chelate aluminum from mature erythrocytes. Hemoglobin level, hematocrit measurement, and mean cell volume showed significant improvement (p less than 0.001). Ten patients showed normalized mean cell volume after 6.2 +/- 2 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reduced selenium status of patients with asthma

1. Selenium is an essential component of glutathione peroxidase (GSH-Px, EC 1.11.1.9), an enzyme which helps protects cells against damage caused by free radicals and hydroperoxides. 2. We report the plasma, whole blood and platelet concentrations of selenium, and whole blood and platelet activities of GSH-Px, in 49 patients with asthma, 23 of whom had coexisting eczema, and 76 healthy control subjects. 3. The asthmatic patients had significantly lower concentrations of selenium measured in plasma (P less than 0.001) and whole blood (P less than 0.001), but not in platelets. When the data were summarized as odds ratios there was a highly significant 3.54- and 5.08-fold increased probability of asthma observed for the lower range of plasma and whole blood selenium concentrations, respectively. 4. No overall decrease in platelet or whole blood GSH-Px activity was found when the asthmatic and control groups were compared. 5. Although patients with symptomatic asthma have a reduced selenium status, this does not appear to influence the antioxidant capacity of their circulating blood cells.     

Midazolam kinetics

The effect-kinetics of the new benzodiazepine midazolam was evaluated in six subjects after single oral (7.5 and 15 mg) and intravenous (0.075 mg/kg) doses and infusion programs. The drug is bound to plasma proteins by 94%, and less than 0.5% is excreted unchanged in urine. Hepatic elimination is rapid: t1/2 beta is 2.4 +/- 0.8 hr (mean +/- S.D) and total body clearance is 283 +/- 43 ml/min (plasma) or 502 +/- 105 ml/min (blood). This substantial first-pass effect leads to bioavailability of only 44%, despite very rapid absorption (t1/2abs = 0.23 +/- 0.37 hr) after oral dosing. There is good intraindividual linear correlations (r between 0.68 and 0.97) between plasma levels and dynamic effects, as assessed by the d2 letter cancellation test and a sedation index formed from visual analogue scales.     

Blood and liver selenium concentrations in patients with liver diseases

To study the relation between blood and liver selenium levels in hepatic disorders we measured the selenium concentrations of whole blood, serum and liver tissue obtained at laparoscopy in 17 patients with different kinds of liver diseases. As compared to healthy controls the mean concentration of selenium was decreased by 24% (p less than 0.001) in the whole blood of the patients (n = 15). Similarly, the mean concentration of selenium in serum was 35% lower in the patients than in the controls (p less than 0.001). As compared to the control samples obtained at autopsy the selenium content of liver was decreased by 13% (p less than 0.05) in the patients. Significant positive correlations were found between the selenium content of the liver and the whole blood (r = 0.62, p less than 0.05) as well as also between liver and serum (r = 0.52, p less than 0.05) selenium concentrations. In conclusion, the present study suggests that in patients with liver disorders the selenium concentrations are decreased not only in the blood but also in the liver tissue. Whether this means a decreased activity of hepatic glutathione peroxidase and, further, an increased possibility of oxidative cell injury, remains open.     

Atomic absorption spectrometric determination of selenium in human blood components

We separated blood from five healthy blood donors into plasma, erythrocytes, platelets, and leukocytes; counted the number of cells in each fraction; and determined the selenium content of each component by hydride generation atomic absorption spectrometry. The mean (+/- SD) selenium concentrations and amounts measured were as follows: whole blood 102.3 +/- 16.1 micrograms/L, plasma 76.9 +/- 10.6 micrograms/L, erythrocytes 13.7 +/- 2.8 ag per cell, platelets 4.8 +/- 1.1 ag per cell, and leukocytes 99 +/- 26 ag per cell.     

Increased elastase-alpha 1-antitrypsin complex in fulminant hepatic failure: relationship to bacterial infection and activation of coagulation.

To study the effect of infection, a frequent complication of fulminant hepatic failure (FHF), on the release of elastase from polymorphonuclear leucocytes and its inhibition in circulation we have measured the concentrations of alpha 1-antitrypsin, which binds and inhibits elastase in the circulation, and of elastase-alpha 1-antitrypsin complex, in 30 patients with FHF. Elastase-alpha 1-antitrypsin complex was significantly increased in FHF as compared to controls (303 +/- 51 micrograms/l compared to 37 +/- 5 micrograms/l; n = 10; P less than 0.001) demonstrating activation of leucocytes in FHF. Infection caused greater release of leucocyte elastase, complex levels were significantly greater in patients who were infected when compared to those who were not (463 +/- 84 micrograms/l; n = 13 compared to 180 +/- 46 micrograms/l; n = 17; P less than 0.01). Also patients who survived had significantly lower complex levels than those who did not (212 +/- 49 micrograms/l; n = 18 compared to 440 +/- 94 micrograms/l; n = 12; P less than 0.02). alpha 1-Antitrypsin activity was not significantly different from control subjects (0.99 +/- 0.06 U/ml compared to 0.97 +/- 0.05 U/ml). However alpha 1-antitrypsin activity was significantly higher in patients who survived (1.17 +/- 0.05 U/ml; n = 18) compared to those who did not (0.71 +/- 0.03 U/ml; n = 12; P less than 0.001) and patients who died had significantly lower levels than control subjects (P less than 0.01) indicating the importance of maintenance of normal inhibitor levels in patients with FHF. The leucocyte activation and release of elastase in FHF was linked to activation of the coagulation system; elastase--alpha 1-antitrypsin complex levels correlated significantly with thrombin-antithrombin III complex levels (r = 0.68; P less than 0.001) and inversely with fibrinogen (r = -0.71; P less than 0.001).     

Association of secondary hyperparathyroidism with red cell survival in chronic haemodialysis patients

51Cr red cell mass (RCM), 51Cr red cell survival (RCS) and plasma parathyroid hormone (PTH) levels were measured in 27 stable chronic haemodialysis patients with a variable degree of clinical secondary hyperparathyroidism. Included were five patients who had had total parathyroidectomy. The results showed a strong negative correlation between PTH and RCS (r = -0.67, P less than 0.001) and a positive correlation between RCS and RCM (r = +0.53, P less than 0.005). However, the negative correlation between PTH and RCM was weak (r = -0.45, P less than 0.02). When the 13 patients with normal PTH levels (mean 0.18 +/- 0.12 microgram/l) were compared with the 14 patients with raised levels (mean 1.35 +/- 0.71 micrograms/l), there was a marked difference in RCS (P less than 0.005) but no difference in RCM.     

In vivo total antioxidant capacity: comparison of two different analytical methods.

Several methods to assess the total antioxidant capacity (TAC) are available. However, the final value of measured TAC in the sample depends on the procedure used in every specific assay. This makes crucial the comparison of different analytical methods. The aim of our study was to evaluate analytical characteristics and laboratory reliability of two different assays: the ferric-reducing ability (FRAP) assay and a new spectrophotometric test (OXY-adsorbent test, Diacron, Italy). Unselected outpatients referred to the Institute of Clinical Physiology were studied (n = 187, 58 females, 129 males, mean age: 65 +/- 13 years). All blood samples were maintained on ice, centrifuged within 15 minutes after blood collection and then stored at -80 degrees C until performance of assay procedures. OXY assay: The lower limit of sensitivity was 6 micromol HClO/ml. The assay was found to be linear up to 440 micromol HClO/ml (r = -0.99, p < 0.001). Absorbance was linear over a wide concentration range with solutions containing uric acid in purified form (0-1000 micromol/l, r = -0.996, p < 0.001), serum (r = -0.99, p < 0.01) or plasma serially diluted (r = -0.99, p < 0.01). Mean value in plasma samples accounted for 366.2 +/- 7.2 micromol HClO/ml. Mean OXY value in females (353.4 +/- 13.2 micromol HClO/ml) was not different from that detected in males (372 +/- 8.6 micromol HClO/ml). A significant difference was observed between subjects without and with hypertension in serum OXY levels (344.8 +/- 9.9 and 383.2 +/- 10 micromol HClO/ml, p < 0.01, respectively). FRAP assay: The lower limit of sensitivity was 15 micromol/l. Linearity was observed up to 1000 micromol/l (r = 0.998, p < 0.001). Absorbance was linear over a wide concentration range with solutions containing uric acid in purified form (0-1000 micromol/l, r = 0.997, p < 0.001), serum (r = 0.99, p < 0.01) or plasma serially diluted (r = 0.99, p < 0.01). FRAP mean value in plasma samples, evaluated in 102 patients, accounted for 514.1 +/- 19.1 micromol/l. Mean FRAP in females (469 +/- 22.5 micromol/l) was not different from that detected in males (535 +/- 25.6 micromol/l). FRAP vs. OXY: A significant direct relationship was observed when comparing FRAP with OXY levels in the whole population (r = 0.22, p < 0.05). Neither of the methods are expensive and they are speedy and simple to perform. Values are reproducible and linearly correlated to the concentration of antioxidants present in the samples. For this reason, these methods may be considered practicable indicators of total antioxidant capacity, for routinely potential use in every laboratory and useful in all the studies concerning the evaluation of oxidative stress.     

Elevated serum levels of angiotensin-converting enzyme in patients with diabetic retinopathy

Serum levels of angiotensin-converting enzyme (ACE) were measured in 53 patients with type II (non-insulin-dependent) diabetes (25 without ophthalmologic complications, 20 with background retinopathy, and eight with proliferative retinopathy) and in 33 healthy nondiabetic subjects. Diabetic subjects were excluded if they had hypertension, ischemic heart disease, peripheral vascular disease, or an elevated urine albumin level. After an overnight fast, blood was taken for determination of ACE, blood glucose, glycosylated hemoglobin (HbA1), and C peptide levels. Data were analyzed according to the nonpaired Student's t test and linear regression analysis. Levels of ACE were significantly elevated in the whole diabetic group as compared with control subjects (334.0 U/L +/- 97.0 vs 250.5 U/L +/- 85.5, P less than .001). This elevation was more marked in those diabetics with background retinopathy (344.6 U/L +/- 96.8, P less than .001) and proliferative retinopathy (357.3 U/L +/- 93.2, P less than .01); no significant difference was found between ACE levels of diabetics without complications and those of control subjects. No correlation was found between ACE levels and HbA1, blood glucose, or C peptide values. We conclude that ACE levels are elevated in type II diabetes, chiefly in patients with retinopathy. This finding may reflect microvascular damage caused by secretion of ACE by the vascular endothelial cells.     

Red blood cell susceptibility to lipid peroxidation, membrane lipid composition, and antioxidant enzymes in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: To investigate the overall susceptibility of red blood cells (RBC) to lipid peroxidation from patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: The following parameters were measured: RBC malondialdehyde (MDA) production after oxidative stress with H2O2, RBC antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and RBC membrane lipid composition. The levels of plasma vitamin E and serum selenium were also assayed. PATIENTS: Eleven patients on continuous ambulatory peritoneal dialysis. Twenty-one healthy blood donors of similar age were used as normal controls. RESULTS: The MDA formation after H2O2 stimulation was normal in CAPD patients (0.79 +/- 0.1 mumol/gHb versus 0.78 +/- 0.1 in the control group). RBC from CAPD patients also showed a normal SOD activity, a more than adequate vitamin E status, and a peculiar pattern of membrane lipids, with reduced polyunsaturated fatty acids (p less than 0.001) and increased monounsaturated fatty acids (p less than 0.001). Both RBC GSH-Px activity, a selenium-dependent enzyme, and serum selenium levels were significantly lower in CAPD patients, and a significant positive correlation (r = 0.68; p less than 0.02) between the two parameters was found. CONCLUSIONS: This study found a normal sensitivity to oxidant stress in RBC from a group of CAPD patients, despite an impaired GSH-Px activity. The peculiar lipid pattern of RBC membrane, characterized by reduced PUFA and increased MUFA content, may contribute, in addition to adequate SOD activity and vitamin E status, to normal RBC lipid peroxidation.     

Glutathione peroxidase activity, lipid peroxides and selenium status in blood in patients with Down's syndrome

The concentrations of selenium and lipid peroxides and the catalytic activity of glutathione peroxidase were measured in the blood of 6 children (6-16 years of age) and 8 adults (17-27 years old) with Down's syndrome (trisomy 21). The values were compared with those for a control group of age-matched normal people. The selenium concentration in whole blood, erythrocytes and plasma was significantly lower in trisomy 21 patients than in normal subjects (p less than 0.001) in both age groups. No statistically significant differences were observed in selenium concentration in whole blood, erythrocytes and plasma between children and adults in the Down's syndrome group. Glutathione peroxidase catalytic activity in erythrocytes was significantly higher in Down's syndrome children than in healthy children (p less than 0.001). Plasma glutathione peroxidase catalytic activity in both investigated age groups was statistically considerably lower in the Down's syndrome patient group. The concentration of lipid peroxides, expressed as the malondialdehyde concentration, is lower in Down's syndrome patients. No correlation between selenium concentration, glutathione peroxidase catalytic activity and amount of lipid peroxides was found in the trisomy 21 patient group.     

Effect of intranasal histamine on nasal mucosal blood flow and the antidiuretic activity of desmopressin.

The effects of exogenous histamine on nasal mucosal blood flow and the systemic activity of intranasally administered desmopressin, a vasopressin analogue, were studied in normal volunteers. Ten subjects received either saline or histamine (1, 20, 100, and 500 micrograms) by intranasal spray. Maximal nasal mucosal blood flow response, determined by laser doppler velocimetry, demonstrated a significant (P less than 0.05) linear relationship to histamine dose. Eight additional subjects received each of the following intranasal treatments: 20 micrograms histamine followed by 10 micrograms desmopressin; normal saline followed by 10 micrograms desmopressin; 20 micrograms histamine followed by vehicle; or normal saline and vehicle. Nasal blood flow was determined before and after each treatment. Desmopressin activity was assessed by measuring urine osmolality, flow rate, electrolyte, and creatinine concentration for 24 h after each treatment. The effect of histamine and desmopressin was greater than desmopressin alone, with respect to nasal blood flow response (103 +/- 24 vs. 4 +/- 17%, mean +/- SEM, P less than 0.02), initial urine osmolality (520 +/- 123 vs. 333 +/- 75 mosM, P less than 0.03), urine electrolyte (potassium, 45 +/- 11 vs. 28 +/- 7 meq/liter; sodium, 68 +/- 21 vs. 36 +/- 8 meq/liter, P less than 0.03) and creatinine concentrations (95 +/- 23 vs. 60 +/- 13 mg/dl, P less than 0.03), and the duration of decrease in urine flow rate compared with saline and vehicle. These results suggest that the systemic activity of intranasal desmopressin is enhanced by increasing local nasal blood flow and are consistent with increased transnasal absorption of the peptide.     

Radioimmunoassay of human platelet-derived growth factor using monoclonal antibody toward a synthetic 73-97 fragment of its B-chain

A mouse monoclonal antibody toward a 73-97 fragment of human platelet-derived growth factor (hPDGF) B-chain was used to develop a radioimmunoassay (RIA) for serum hPDGF. By the single step procedure of the double antibody technique, the measurable range was 10-1,000 micrograms/l. The coefficients of variation within and between series were 10.2% and 12.1% respectively, and satisfactory dilution curves were obtained for sera from healthy subjects. The hPDGF levels in all plasma samples from 15 healthy subjects examined were below the detection limit (10 micrograms/l), whereas the mean hPDGF concentration (+/- SD) in serum samples of 60 healthy subjects was 31.9 +/- 20.4 micrograms/l. This value was significantly (p less than 0.01) higher than the mean for 21 patients with idiopathic thrombocytopenic purpura (12.6 +/- 4.5 micrograms/l). There was a significant positive (r = 0.481, p less than 0.01) but not a strong (r2 = 0.23) correlation between the peripheral blood platelet counts and serum hPDGF levels of all subjects. This RIA system should be useful clinically for measurement of serum hPDGF.     

Kidney and plasma renin in human renovascular hypertension.

Renin activities were determined in plasma and in single, microdissected juxtaglomerular apparatus in 19 patients with unilateral renal artery stenosis. The mean juxtaglomerular apparatus renin concentration in the stenosed kidneys was 5.5 +/- 1.2 (SEM) mug.l-1.h-1 which is about ten times that of the suppressed renin concentration in the contralateral kidneys (0.6 +/- 0.05 mug.l-1.h-1). On the affected side a positive correlation was found between intrarenal and renal venous renin concentration (r = 0.93; p less than 0.001). Both intrarenal and renal venous renin concentrations of the stenosed kindeys were positively correlated to renin secretion rates, as calculated from renin analysis in plasma from the vena cava and renal veins. No relationship could be demonstrated between intrarenal or renal venous renin concentration and the degree of blood pressure elevation or transstenotic pressure gradient. However, a positive correlation was evident between peripheral plasma renin activity and diastolic blood pressure (r = 0.88; p less than 0.001). Comparative enzyme kinetic analyses of renin from the juxtaglomerular apparatus and renal venous plasma were performed using sheep substrate. The lowest apparent Km-values of renin were found in renal venous plasma from the stenosed kidneys (198 +/- 13 mug/l) compared with the contralateral side (301 +/- 20 mug/l; p less than 0.001). Mean apparent Km-values of juxtaglomerular apparatus renin in the stenosed (270 +/- 36 mug/l) and contralateral (292 +/- 37 mug/l) kidneys did not differ. No significant differences were found between mean apparent Km-values for renin in peripheral plasma of renovascular hypertensive patients and control subjects using either homologous human or heterologous sheep renin substrate. The results suggest that, in addition to the renin concentration other factors are relevant to chronic high blood pressure in renovascular hypertension.     

PLASMA KININ-PRECURSOR LEVELS IN CLINICAL INTESTINAL INFLAMMATION

Plasma kinin-precursor (kininogen) concentrations were measured in the peripheral venous blood of 7 untreated patients with inflammatory bowel diseases, 12 healthy subjects, and 5 uncomplicated fracture cases. The mean plasma kininogen levels were significantly raised (P less than 0.025) in patients with intestinal inflammation (7.0 +/- 1.0 micrograms BK Eq/ml), as compared with the value found in healthy subjects (5.7 +/- 0.7 micrograms BK Eq/ml), and in fracture cases (5.0 +/- 1.2 micrograms BK Eq/ml). The packed cell volume did not differ (P greater than 0.05) between patients and control groups. Thus, the raised plasma kininogen levels observed in patients were not the result of nonspecific changes in plasma volume. It is suggested that raised plasma kininogen might be due to increased synthesis to provide substrate for excessive kinin-formation, to a potent inflammatory agent, or to high synthesis of acute-phase reactants. The possible significance of this observation is discussed.     

Reduced postprandial hyperglycemia after subcutaneous injection of a somatostatin-analogue (SMS 201-995) in insulin-dependent diabetes mellitus

The effect of a new octapeptide analogue of somatostatin (SMS 201-995) on blood glucose and gut hormone levels was studied in 10 C-peptide-negative, insulin-dependent diabetic (IDDM) subjects. On separate days, either 50 or 100 micrograms SMS or placebo was s.c. injected simultaneously with an identical insulin dose 30 min before a mixed meal. Postprandial blood glucose decreased after 100 micrograms SMS s.c. within 30 min from 8.9 +/- 0.7 to 7.8 +/- 0.6 mmol/L (P less than 0.001) and remained at similar levels during 180 min. In contrast, postprandial blood glucose concentration increased after placebo from 9.9 +/- 0.8 to 13.8 +/- 0.9 mmol/L (SMS versus placebo P less than 0.001). Plasma glucagon decreased rapidly after SMS to the limit of detection (P less than 0.001) and remained lowered during 180 min; in contrast, glucagon levels increased after the meal during the placebo study (SMS versus placebo P less than 0.001). Plasma growth hormone concentrations were significantly lower after SMS than after placebo (P less than 0.05). SMS abolished completely the postprandial increase in plasma gastrin and pancreatic polypeptide (PP) concentrations. Plasma free fatty acid (FFA) and triglyceride concentrations decreased after SMS, reaching significantly lower levels than after placebo (P less than 0.05 and P less than 0.01), respectively). Plasma SMS concentration increased rapidly after s.c. administration of SMS; its appearance preceded that of plasma free insulin after s.c. insulin injection. Fifty micrograms SMS was similarly effective as 100 micrograms in decreasing blood glucose, triglycerides, glucagon, and gut hormone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radioimmunoassay of human plasma lecithin-cholesterol acyltransferase.

A sensitive and precise competitive-displacement double-antibody radioimmunoassay was developed for the human plasma enzyme lecithin-cholesterol acyltransferase (LCAT; Ec 2.3 1.43). The ability of plasma from various animal species to displace labeled human LCAT from goat anti-human LCAT could be ranked in the following order: man and sheep > nonhuman primates > cat or dog > pig > rabbit or guinea pig > mouse > rat. Normolipidemic subjects had levels of LCAT of 6.14 +/- 0.98 micrograms/ml (mean +/- SD, n = 66). Subjects with dysbeta-lipoproteinemia had the highest plasma LCAT levels (7.88 +/- 0.39 micrograms/ml, n = 7, P < 0.05), followed by hypercholesterolemic subjects (7.00 +/- 1.30, n = 41) and hypertriglyceridemic subjects (6.96 +/- 1.3, n = 10). LCAT-deficient subjects had the lowest enzyme levels (0.89, 0.83, and 0.05 micrograms/ml, respectively, and two subjects with no detectable enzyme). Males had lower LCAT levels (6.42 +/- 1.05 micrograms/ml, n = 90, for all subjects; 5.99 +/- 1.03, n = 44, for normolipidemics) than females (7.01 +/- 1.14, n = 34, for all subjects P < 0.01; 6.44 +/- 0.79, n = 22, for normolipidemics, P < 0.01). LCAT levels correlated significantly with total cholesterol (males, r = 0.384, P < 0.001; females, r = 0.519, P < 0.002); and total triglyceride (only in females, r = 0.512, P < 0.002). LCAT levels in females correlated inversely with HDL cholesterol (r = 0.341, P < 0.05) and apoprotein D (r = 0.443, P < 0.02), but no such relationship existed in males.     

Increased plasma fibronectin concentration in diabetic patients with microalbuminuria

Raised levels of plasma fibronectin (PF), an alpha 2-glycoprotein produced by vascular endothelia, have been previously described in diabetic patients with retinopathy and overt nephropathy. The aim of this study was to investigate whether the presence of microalbuminuria is associated with increased PF concentrations. Twenty Albustix-negative diabetic outpatients with microalbuminuria [median albumin excretion rate (AER): 30.2 micrograms/min; range 12.1-194 micrograms/min] were compared with 58 sex- and age-matched patients without microalbuminuria (median AER 3.1 micrograms/min; range 0.8-12 micrograms/min) and 34 control subjects (median AER 2.8 micrograms/min; range 0.8-12.1 micrograms/min). Mean PF was significantly higher in the group with microalbuminuria (406.7 +/- 85.5 micrograms/ml) than in the group without it (325.3 +/- 76.5 micrograms/ml or in control subjects (334.5 +/- 76 micrograms/ml; P less than .05). PF increase associated with microalbuminuria was independent of the presence of retinopathy. Furthermore, in the whole group of diabetic patients, PF was significantly correlated with AER (r = .33; P = .003). Such correlation also remained significant (P = .0002) after covariance analysis by a stepwise discriminant procedure taking into account age, duration of disease, sex, blood pressure, body weight, therapy, and HbA1. In conclusion, PF increase is associated with microalbuminuria independent of the other considered variables; its role as a possible marker for early diabetic nephropathy remains to be fully clarified.     

Glutathione peroxidase activity, selenium and lipid peroxides levels in blood of cancer children

The concentrations of whole blood and plasma selenium, plasma lipid peroxides and the glutathione peroxidase activity in plasma and erythrocytes were measured in untreated and treated children with neuro- (n = 23) and nephroblastoma (n = 32) aged 6 months to 15 years. The patients were divided into the following groups: 0.5-1, 1-3, 3.5-6 and 8-15 years old. In all the groups of cancer patients investigated selenium concentration in whole blood and plasma and glutathione peroxidase activity in erythrocytes and plasma were significantly lower than in the age-matched healthy children. The concentrations of lipid peroxides in plasma of children with cancer was higher than in the age-matched control group. No differences were observed between the levels of the determined parameters in children with neuro- and nephroblastoma. Nor were there any differences in the determined parameters between children before and during treatment with cytostatics and between children at different stages of the disease. A significant linear correlation was found between plasma selenium concentration and glutathione peroxidase activity in the erythrocytes and plasma of children with cancer.     

Effect of furosemide on plasma concentration and beta-blockade by propranolol.

Although propranolol and furosemide are used together for hypertension, the effects of furosemide on plasma levels and beta-blocking action of propranolol are not known. Ten healthy subjects received propranolol 40 mg orally; the mean plasma propranolol levels in 60, 90, 180, and 300 min were 85 +/- 16, 90 +/- 7, 82 +/- 8, and 58 +/- 8 ng/ml. Propranolol was then given together with furosemide (25 mg orally) and the propranolol blood level was measured. Mean propranolol plasma levels were 106 +/- 11 ng/ml at 60 min, 120 +/- 12 ng/ml at 90 min (p less than 0.01), 102 +/- 8 ng/ml at 180 min (p less than 0.05), and 78 +/- 8 ng/ml at 300 min (p less than 0.01). Six additional subjects were given an infusion of 1 microgram/min isoproterenol increased by 0.5 microgram/min every 2 min until the heart rate rose by 25% after oral administration of furosemide 25 mg. This procedure was repeated after propranolol (40 mg orally) and propranolol with furosemide (25 mg orally). The amount of isoproterenol which raised the heart rate by 25% was 2.6 +/- 0.3 micrograms after furosemide alone and 17.7 +/- 2 micrograms after propranolol (p less than 0.01). After propranolol with furosemide the dose of isoproterenol required to elevate heart rate by 25% was 109 +/- 15 micrograms (p less than 0.001).