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We studied serum lipid and lipoprotein changes before and after induction treatment in 25 acute nonlymphocytic leukemia (ANLL) and in 18 acute lymphocytic leukemia (ALL) patients in order to investigate their relationship with disease activity and their prognostic relevance. ANLL at diagnosis is associated with significantly low levels of all lipid parameters, the same applies to ALL patients apart from plasma triglycerides and very-low-density-lipoprotein cholesterol (VLDL-C) which are significantly higher than in the normal population. In ANLL responders, after effective chemotherapy, a significant increase of total cholesterol, low-density-lipoprotein cholesterol (LDL-C) and apolipoprotein B levels, without changes of high-density-lipoprotein cholesterol (HDL-C) values, is observed. A further decrease of total cholesterol and LDL-C was found in nonresponders and in ANLL responders treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), known for its cholesterol-lowering action; in fact after the completion of GM-CSF therapy, these parameters returned progressively toward normal values. In ALL responders an increase of total cholesterol, HDL-C and apolipoprotein A1 with a simultaneous decrease of triglycerides and VLDL-C is evident; no variation was found in the nonresponder group. These results suggest a close correlation between serum lipids and acute leukemia: total cholesterol and LDL-C in ANLL, and HDL-C and VLDL-C in ALL may be considered reliable markers of complete remission and may be useful in the follow-up of leukemic patients.

The aim of this study was to determine the most appropriate urine collection for detecting differences in the excretion rates of albumin, gamma glutamyl transpeptidase (GGT) and N-acetyl-beta-D-glucosaminidase (NAGA) between normotensive subjects and hypertensive patients on treatment. Twenty treated hypertensive patients, mean (SEM, standard error of mean) age; 52.2 (6.2) years and 20 normotensive subjects, mean age 49.2 (4.2) years, were studied in a consecutive sampling design. Urinary excretion rates of albumin, GGT and NAGA were determined in consecutive timed urine samples collected overnight and during 3-5 h the next morning. Mean (SEM) overnight excretion rates for albumin, GGT and NAGA for normotensive subjects were 11.05 (1.18) micrograms/min, 17.00 (2.20) mU/min and 6.55 (0.39) mU/min, respectively, which were significantly lower than those of hypertensive subjects which were 20.77 (2.14) micrograms/min, 21.84 (1.65) mU/min and 10.92 (0.87) mU/min, respectively (P < 0.05). The mean (SEM) percentage increases in urinary albumin, GGT and NAGA in morning urine collections of normotensive subjects of 15.22 (3.88)%, 34.04 (6.45)% and 11.54 (3.63)%, respectively were significantly lower than 107.03 (15.04)%, 121.96 (16.71)% and 72.75 (7.50)% found in hypertensive patients (P < 0.05). These data suggest that were urinary albumin and tubular enzyme excretion to be used as correlates of hypertensive renal damage, ambulatory urine collections may be more sensitive than overnight collections.

1. In the present study we have investigated the effects of the relatively low plasma concentrations of gemfibrozil (GFZ) found in clinical practice on the oxygen dissociation curve (ODC) of erythrocytes. 2. ODCs were measured at 30 degrees C and 37 degrees C and at pH 7.4: a) both on HbA solution and erythrocytes incubated in vitro with gemfibrozil and clofibric acid; b) on erythrocytes from healthy volunteers treated with a single oral dose of gemfibrozil. 3. These experiments showed a significant drug-induced shift of the ODC towards lower O2 affinity values without any significant modification of metabolic parameters of erythrocytes such as intracellular pH and intraerythrocytic levels of ATP and DPG. 4. In our experimental conditions gemfibrozil appears to lower both in vitro and in vivo, the partial pressure of oxygen required to give 50% of the haemes saturated with oxygen (P50) of erythrocytes from the control value of 24 +/- 0.5 mm Hg to 29 +/- 0.5 mm Hg (mean +/- s.d.; P < 0.02 by ANOVA). 5. These data clearly indicate that therapeutic doses of gemfibrozil may influence the oxygen transport properties of red cells. This effect could have relevant pharmacological and toxicological implications.

Current studies suggest a derangement of the cholesterol homeostasis in certain types of leukaemia. The low serum cholesterol levels observed in patients with AML have been related to the tumoral mass and to the disease activity. Only a few studies have taken into consideration a possible change of the serum lipids in ALL. The aim of this study was to evaluate a possible prognostic significance of serum levels of total cholesterol (TC), triglycerides, HDL-C, LDL-C, VLDL-C, apolipoproteins A1 and B and lipoprotein (a), investigated in 10 newly diagnosed ALL patients before and after induction treatment. At diagnosis all these parameters were not significantly different in our patients vs control group except cholesterol and HDL-C levels, which were significantly lower. After the induction treatment, we found a significant increase of HDL-C and Apo A1 values only in those patients that achieved a complete remission. These results support the idea that some serum lipids, such as HDL-C and Apo A1, may have a role as early and reliable markers of the effectiveness of chemotherapy.

The aim of this study was to investigate possible abnormalities in salivary electrolytes in hypertensives treated with ace-inhibitors (ACE-I) or calcium antagonists (Ca-ANT) at low or normal sodium intake. Hypertensives treated with ACE-I (n.14) or Ca-ANT (n.22) and 13 normotensives were studied during normal or restricted Na intake. Na, K, Ca, Mg and Cl were determined in saliva samples collected by using a standardized adsorption procedure (SALIVETTE). Na intake was evaluated by determination of the 24-hr urinary Na excretion. Similar concentrations of Na, K, Ca, and Cl were found in normotensives and in hypertensives treated with ACEI or Ca-ANT both at low or normal Na diet. Magnesium in saliva appeared reduced in ACEI-treated hypertensives (0.28 +/- 0.06 mmol/l) in comparison to the similar values of normotensives (0.53 +/- 0.05) and Ca-ANT treated hypertensives (0.54 +/- 0.07). In normotensives and in treated hypertensives lowering of Na intake did not change the salivary content of Ca, Mg and Cl but produced in saliva a reduction of Na associated to a rise in K. Salivary Na/K ratio was significantly correlated with 24 hr urinary Na excretion in normotensives (r = 0.77; p < 0.05) and in hypertensives treated with ACE-I (r = 0.74; p < 0.05) or Ca-ANT (r = 0.62; p < 0.05). The low salivary magnesium in ACE-I-HT may have a role in the occasional ACEI-dependent dysgeusia. Salivary Na/K ratio may be used as a rough index of Na intake in treated hypertensives.

Although inflammatory or degenerative changes in salivary glands have been demonstrated in genetic animal models of diabetes mellitus and in experimental diabetes, no information is available in diabetics on the possible leakage in saliva of cytosolic enzymes as markers of salivary cell injury. Aspartate (GOT) and alanine (GPT) aminotransferases and lactate dehydrogenase (LDH) were determined in saliva samples collected by the Salivette method from well-controlled insulin-dependent (IDDM n = 11) and non-insulin-dependent (NIDDM n = 18) diabetic patients and from age-cross-matched healthy subjects (n = 33). In IDDM salivary concentrations of GOT (112.55 +/- 23.94 UI/L) and LDH (1120.27 +/- 168.31 UI/L) were similar to those found in the NIDDM (90.94 +/- 19.64, and 1255.43 +/- 221.40 UI/L respectively), but higher (p < 0.05) than those observed in normal subjects (33.09 +/- 3.71, and 423.58 +/- 39.94, UI/L respectively). GPT was higher in NIDDM than IDDM, which in turn was higher than in normal subjects (42.78 +/- 14.72, 16.45 +/- 3.74 and 6.85 +/- 1.52 UI/L respectively). Salivary and serum values of GOT, GPT and LDH were not correlated. Determination of cytosolic enzymes in saliva may be useful for monitoring the diabetic involvement of salivary glands.

Serum fructosamine levels in 36 subjects with various types of multiple myeloma and in 64 normal controls were evaluated by means of a Nitroblue tetrazolium colorimetric assay. Only the IgA myeloma group showed significantly raised serum fructosamine values (P less than 0.001). In the IgG myeloma group, which showed a higher mean serum protein concentration, serum fructosamine levels were not significantly different from controls. The study shows that elevated IgA levels do influence serum fructosamine and this effect should be taken into due consideration in order to avoid possible misinterpretations in evaluating this widely used index of glucose metabolism.

The case of a 15-year-old boy with a pineal germinoma is reported. The patient first underwent a ventriculoperitoneal (VP) shunt followed by a stereotactic biopsy, then, because of the rapidly deteriorating neurological status, an emergency craniotomy with subtotal removal of the tumour was performed. Two months after surgery, a left femoral metastasis and extensive peritoneal lesions became evident; they were regarded as due to haematogenous and VP shunt spread of the germinoma. At that time, extremely high serum levels of placental alkaline phosphatase were detected. The patient died 6 months after the initial diagnosis. The occurrence of extraneural metastases as well as of shunt related peritoneal deposits from primary intracranial germinoma is discussed. As far as we know this is the first reported case of a combination of haematogenous as well as VP shunt spread of a pineal germinoma.

A simple test for the evaluation of the thromborheological properties of native blood was developed. The test measured the filtration pressure produced by the 24-sec passage of 1.5 ml of native blood through a polycarbonate filter with pores of 5 mu. Healthy subjects, patients with symptomatic atherosclerosis and patients with miscellaneous non-vascular disorders taking neither drugs active on red blood cell deformability nor on platelet and hemostatic functions were examined by this test. No correlations between filtration pressure of native blood and fibrinogen, PTT, factor VIIIR:Ag and hematocrit values were found. The results suggest that this test may be useful in the detection of thrombophilic patients and in monitoring the effectiveness of drugs known to be active on red blood cell deformability and/or on platelet and hemostatic functions.

A system has been developed in our Hospital Clinical Chemistry Laboratory with the aid of a minicomputer on line with SMAC. The programs are in Basic and comprise management of patient samples and of reference sera, on-line acquisition of analytical data, checks of error reporting and of abnormal result values, real time processing of quality control parameters and data transfer on floppy disk. An efficient and easy monitoring of the chemical procedures and result reliability is achieved together with instrument performance optimization.

Endothelial injury and platelet activation, mechanisms known to be involved in vascular lesions, may promote the development of cardiovascular disorders possibly associated with mental stress. Plasma markers of platelet activation (beta-thromboglobulin, BTG) and of endothelium activity (factor VIII/von Willebrand factor, FVIII/vWf) and plasma renin activity (PRA) were determined in 17 healthy normotensive volunteers and in 21 hypertensives without target-organ damage before and after mental stress (a colour-word conflict test). The aim of the study was to compare cardiovascular reactivity with the stress-induced changes in platelet and endothelium activity. Individual responses in BTG and factor FVIII/vWf after the colour-word conflict test were markedly different, but significant mean increases were observed in both groups with no difference in the degree of response and in the percentage of responders. No correlations were found among the changes in plasma variables or between cardiovascular reactivity (systolic and diastolic blood pressure and heart rate) and the changes in BTG, FVIII/vWf and PRA. These findings suggest that hypertensive patients do not have an abnormal platelet or endothelium reactivity to mental stress, at least when the disease is free of vascular complications. This dissociation of stress-induced variability in BTG and FVIII/vWf and cardiovascular reactivity indicates that these indices could be used as independent markers of mental stress.

Blood collected in citrate-phosphate-dextrose-adenine (CPDA-1) containing transfusional bags, was weekly tested throughout a 35 day period. Biochemical assays included plasmatic glucose, electrolytes, free Hb, acid-base balance and hemogasanalysis. Intraerythrocytic ATP and 2,3 DPG were also determined. Results show that an almost total 2,3 DPG depletion occurs during the first three weeks, whereas intracellular ATP are about 50% of the initial values, at the same time. Lowering of pH is also maximal at the third week. pCO2 variation pattern is biphasic: an early increase due to HCO3- titration by lactic acid arising from red cells glycolysis, followed by a decrease probably due to plastic bag permeability to CO2 itself. The percentage of O2Hb also rises during blood storage: this might be the combined result of increase in pO2 and decrease in 2,3 DPG content. A rise of free Hb was obtained; extracellular K+ levels underwent a sixfold increase in 35 days. The mechanism of relative variations of these parameters and the gas transport are discussed. Some of these parameters might be used as routine controls to asses viability and functional status of stored red cells for transfusional use.

We measured the urinary excretion of beta-thromboglobulin in timed urine samples collected by 2 groups of healthy volunteers, (group I, n = 20, mean age 34 years, group II, n = 15, mean age 64 years) and by patients (n = 40) with symptomatic atherosclerotic diseases. Older healthy subjects were found to excrete high amounts of BTG in comparison to young subjects (302.25 +/- 50.61 vs 219.65 +/- 59.31 ng/day, P less than 0.05). Higher (P less than 0.01) levels of urinary BTG were observed in patients with coronary (427.61 +/- 179.96 ng/day), cerebral (422.13 +/- 223.2 ng/day) and peripheral (454.16 +/- 269.05 ng/day) arterial diseases and in diabetic patients with diffuse vascular complications (613.71 +/- 253.07 ng/day). The diurnal variability of BTG excretion, measured as coefficient of variation (C.V. %) of the mean daily excretion rate, was higher (P less than 0.001) in atherosclerotic patients (70.59 +/- 26.57) as compared with the similar values observed in the control groups of young (32.05 +/- 14.54) and older subjects (26.38 +/- 8.4). Comparable diurnal variabilities of the creatinine excretion rate were observed in the control groups and in patients. These data indicated that in vivo platelet activation may occur in atherosclerotic patients with a distinctive high fluctuation rate.

In vitro thrombolytic experiments were performed in a system composed of a radioactive clot (125I fibrinogen) perfused by whole anticoagulated blood to which a small amount of urokinase (UK) was added by continuous infusion. At various intervals a small aliquot of blood was drawn from the system and assayed for fibrinogen, plasminogen and alpha 2-antiplasmin. Results were correlated with the degree of thrombolysis measured continuously as decrease of clot radioactivity by a ratemeter connected to a recorder. The coefficients of correlation between fibrinogen, plasminogen and thrombolysis were -0.45 and -0.46, respectively (p less than 0.001). The highest coefficient of correlation was observed between alpha 2-antiplasmin change and thrombolysis (-0.84; p less than 0.001). Results indicate that the initiation of an effective thrombolytic state induced by UK required the depletion of about 50% of alpha 2-antiplasmin. The measurement of alpha 2-antiplasmin during UK therapy at low or moderate dosage appears to be useful for dosage adjustments leading to the development of a thrombolytic state.

Different procedures are currently used in the urine beta-thromboglobulin (BTG) assay. We investigated the reliability of limited urine collections and of different expressions of urine BTG results (concentration, urine BTG/creatinine ratio) for the measurement of hourly or daily BTG excretion rates. BTG was measured by a sensitive RIA method in various urine collections of normal subjects (n.80) and patients (n.120) with miscellaneous diseases where an enhanced in-vivo platelet activation could be expected. The BTG concentration in a 6-hour urine collection appeared to change in relation to the urine flow rate (r = -0.53 in normals, r = 0.27 in patients, p less than 0.01) and urine osmolality (r = 0.46 in normals, r = 0.31 in patients, p less than 0.01). In both normals and patients not a very good correlation was observed between the urine BTG/creatinine ratio and the BTG excretion rate (r = 0.54 and r = 0.48; p less than 0.001, respectively). Variable coefficients of correlation (r = 0.83-0.34) were observed between the BTG excretion rate of single voidings of the morning, afternoon-evening and night and the daily BTG excretion both in normals and patients. Reliable measurements of the BTG in urine should be expressed as the hourly excretion rate in a given period of the day for limited urine collections or as the daily excretion for 24-hour urine collections.

We propose a statistical procedure for long-term quality-control of laboratory instruments, including daily, day-to-day, and monthly evaluations. The procedure is based on the unique and unequivocal interpretation of five results for control sera by calculation of a Reliability Index and further manipulations of this unitless parameter. This method, which we have tested during the past two years, allows for monitoring analytical performance and making comparisons with results of interlaboratory surveys. The monthly analytical variability, expressed as "total error," is an indicator of the clinical usefulness of analytical results.

Von Willebrand factor (vWF) is known to play a relevant role in the development of atherosclerotic lesions by promoting platelet adhesion to injured endothelial cells. An increase in cytosolic calcium has been shown to be associated with the in vitro release of vWF from endothelial cells. The aim of our investigation was to examine the effect of some calcium channel blockers on the release of vWF antigen (vWF:Ag) induced by exercise in two groups of eight healthy subjects during a randomized crossover study between placebo and calcium channel blockers. Placebo and verapamil (80 mg) or nicardipine (10 mg) were given orally at an interval of 2 weeks three times on the day before and once on the morning of the study day. Measurements of plasma vWF:Ag were made at rest and after a progressive maximal exercise on a cycloergometer. A significant increase in absolute values of vWF:Ag was observed after exercise in the subjects given a placebo in both verapamil (0.397 +/- 0.074 U/ml) and nicardipine (0.327 +/- 0.036 U/ml) groups, p less than 0.05. With use of verapamil the rise in vWF:Ag was blunted and not significant (0.123 +/- 0.081 U/ml) whereas a larger increase in vWF:Ag was found in the subjects given nicardipine in comparison with placebo (0.593 +/- 120 U/ml; p less than 0.05). No correlations were observed between exercise-induced changes in systolic or diastolic blood pressure, heart rate, blood lactate level, or pH and vWF:Ag changes in the subjects given a placebo or in those given calcium channel blockers.(ABSTRACT TRUNCATED AT 250 WORDS)

The activities and subcellular distribution of the following enzymes: NADH oxidase, alkaline phosphatase, beta-glucuronidase and ATPase, were assayed in human mononuclear and polymorphonuclear leucocytes and in particular the contamination and integrity of the mitochondrial fractions were evaluated with this new separation procedure. Results show that maximal contamination was found to be that from lysosomal beta-glucuronidase especially in polymorphonuclear leucocyte mitochondria fractions. Furthermore oligomycin-sensitive ATPase data suggest that mitochondria do not decrease in number or lose their integrity to a great extent. Controversial p-nitrophenyl-phosphatase activity was also found to be present in polymorphonuclear and mononuclear leucocytes granular-soluble fractions.