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Nitric oxide (NO) is formed by a class of NO synthases (NOS), which convert arginine into citrulline. A decreased in vivo NO availability can be the result of an increased NO inactivation or a decreased NO production. The latter can be assessed by measurement of isotopic enrichment of plasma citrulline during infusion of isotopically labeled arginine. The potential of high-performance liquid chromatography (HPLC) coupled to mass spectrometry (MS) to determine enrichments of [15N2]arginine and [15N]-citrulline in plasma during infusion of [15N2]arginine in humans was investigated. Two types of MS instruments were evaluated: a sector-type mass spectrometer equipped with a frit fast-atom bombardment (FAB) interface and a quadrupole instrument with electrospray ionization (ESI). FAB-MS appeared to be unsuitable for determination of isotope ratios, because background ions influenced the observed isotope ratio in an unpredictable way. In combination with either off- or on-line reversed-phase HPLC, ESI-MS proved to be a more reliable technique. However, the amount of material that is introduced in the mass spectrometer is critical and should be carefully controlled. During infusion of [15N2]arginine in 14 healthy subjects, a mean arginine-to-citrulline conversion rate of 0.22 +/- 0.07 (SD) mumol.kg-1.h-1 was found. In 4 subjects who received an intravenous infusion with the NOS antagonist L-NMMA, the conversion rate decreased from 0.30 +/- 0.14 to 0.10 +/- 0.06 mumol.kg-1.h-1. It is concluded that ESI-MS in combination with HPLC can be successfully applied for determination of arginine and citrulline enrichments in plasma, thus providing a useful tool for assessment of in vivo NO production.

To investigate whether sodium fluoride (NaF) is able to prevent bone loss in patients treated with corticosteroids (Cs), we performed a randomized double-masked, placebo-controlled trial with 44 Cs-treated patients without established osteoporosis, defined as the absence of previous peripheral fractures and vertebral deformities on radiographs. The effects of NaF (25 mg twice daily) and placebo on the bone mineral density (BMD) of the lumbar spine and hips were compared at baseline and at 6, 12, 18 and 24 months. After 2 years, the BMD of the lumbar spine had decreased in the placebo group by 3.0% (95% CI: -4.9% to -1.0%; p < 0.01); in the NaF group there was a statistically insignificant increase in BMD of 2.2% (95% CI: -0.8% to +5.3%). The difference in the changes in BMD between the two groups was +5.2% (95% CI: +1.8% to +8.6%; p < 0.01). In the hips, BMD had decreased after 2 years in both groups: in the placebo group by -3.0% (95% CI: -5.0% to -1.0%; p < 0.05) and in the NaF group by 3.8% (95% CI: -6.1% to -1.5%; p < 0.01). The difference in the changes in BMD between the two groups was not significant: +0.8% (95% CI: -2.1% to +3.8%). Three vertebral deformities were observed in the placebo group and one in the NaF group (insignificant difference), while no peripheral fractures occurred during the study period. It is concluded that in Cs-treated patients without established osteoporosis NaF prevents bone loss in the lumbar spine but does not have a positive effect on the BMD of the hips

The absolute bioavailability and other pharmacokinetic parameters of two fluoride formulations were investigated in 13 healthy volunteers, aged 61-70 years.The following formulations were administered, under fasting conditions, in a single-dose three-way cross-over design: tablets of 76 mg disodium monofluoro phosphate (MFP, equivalent to 10.0 mg F- ion), enteric-coated (e.c.) tablets of 25 mg sodium fluoride (NaFor, equivalent of 11.3 mg F- ion), and an isoosmotic aqueous injection solution (4 ml) of 22.1 mg sodium fluoride (NaFiv, equivalent of 10.0 mg F- ion). There was a wash-out period of at least one week between each administration. Blood was sampled before and during a 24-hour period after administration. For F- excretion urine was sampled 48 hours before (baseline) and over the 48 hours after the administration.The mean t1/2 values of the three formulations were 8.3, 8.7 and 8.3 h for MFP, NaFor and NaFiv respectively, and were not significant different. Mean Cmax after MFP was significantly higher than after NaFor [344 vs 142 micrograms.l-1]. Mean tmax for MFP was shorter than for NaFor [1.1 vs 4.6 h]. MFP had significantly higher bioavailability [102.8%] than NaFor [64.2%].The MFP formulation showed higher bioavailability with smaller variation than the NaFor formulation. MFP is preferable, therefore, for fluoride therapy in clinical practice, and changing from NaFor to MFP will require adjustment of the dose.

OBJECTIVE: To examine the effect of high dose corticosteroid pulse treatment (three times 200 mg dexamethasone intravenously in eight days) on calcium and bone metabolism in 17 consecutive patients with active rheumatoid arthritis (RA). METHODS: Bone formation was quantified by measurement of serum alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (pro-I-CPP) concentrations. Bone resorption was measured by urinary excretion of calcium, hydroxyproline, (free and total) deoxypyridinoline (Dpyr), (free and total) pyridinoline (Pyr), and serum concentrations of the carboxyterminal cross linked telopeptide of type I collagen (I-CTP). Disease activity of RA was measured by erythrocyte sedimentation rate, C reactive protein, and Ritchie and Thompson joint scores. RESULTS: Disease activity was initially high, and decreased during corticosteroid pulse treatment and the following five weeks. Osteocalcin, alkaline phosphatase, and pro-I-CPP concentrations were initially within normal limits, while I-CTP, Dpyr, and Pyr were increased. Osteocalcin and pro-I-CPP concentrations decreased (p < 0.01) during corticosteroid pulse treatment, but rapidly returned to baseline after the treatment. No changes were observed in alkaline phosphatase and urinary excretion of calcium and hydroxyproline. Bone resorption measured by serum I-CTP and urinary excretion of Pyr and Dpyr was unchanged or decreased (p < 0.05-0.01), depending on the time of measurement and the parameter measured. CONCLUSIONS: In these patients with active RA, bone resorption was increased, while bone formation was within normal limits. During high dose corticosteroid pulse treatment, bone formation was only transiently decreased, while markers of bone resorption were unchanged or decreased. Because corticosteroid pulse treatment has only a short term negative effect on bone formation, and because it probably reduces bone resorption, at least partly as a result of the decreased disease activity, the effect of corticosteroid pulse treatment on bone may be assumed to be relatively mild.

We studied the effects of a single dose (100 mg orally) and repeated administration (100 mg o.d. for 7 days) of FK453, a novel adenosine-1 receptor antagonist, on renal sodium handling and blood pressure in eight patients with essential hypertension. Within 60 minutes after administration of FK453, sodium excretion increased threefold. This occurred in the absence of a change in renal hemodynamics, assessed from inulin and para-aminohippurate clearance, and was accompanied by increased fractional excretion of lithium, phosphate, and uric acid and by increased excretion of calcium and magnesium. Maximal free water clearance data showed an increase in maximal urine flow and distal delivery term and a decrease in the diluting segment reabsorption term. FK453 also decreased blood pressure and increased heart rate, but this did not occur until about 3 hours after ingestion, that is, when the natriuresis was already over. The natriuretic effect of FK453 was short-lasting, and continued use of FK453 was in fact accompanied by some net sodium retention. Blood pressure on the seventh day before FK453 treatment was not different from blood pressure before administration of the first dose of FK453. Again an acute natriuretic response followed, although less than after the first dose. Changes in intrarenal sodium handling parameters, blood pressure, and heart rate were similar to those seen after the first dose. The natriuretic and hypotensive effects of FK453 indicate that adenosine-1 receptor activity plays a role in the regulation of blood pressure and renal sodium handling in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of factors related to the need for transfusion in premature infants.Descriptive.The need for transfusion in premature infants was determined in 2 academic centres: University Medical Center Utrecht and Leiden University Medical Center, The Netherlands. The data had been acquired in another study. The factors under study were: hospital, pregnancy duration, birth weight, gender, time of clamping of the umbilical cord, total volume of blood sampled for diagnostic purposes, number of days of mechanical ventilation, total duration of admission and duration of the admission to the Neonatal Intensive care unit. Both hospitals followed the national interdisciplinary practice guideline 'Blood transfusion'.The total volume ofsampled blood for diagnosis, the duration of the mechanical ventilation and the admission period were related to a greater need for transfusion. On the other hand, the chance of transfusions diminished with longer pregnancy duration or increased birth weight. The difference in need for blood transfusion between both centres was significant. The total volume of transfused erythrocytes showed a strong correlation with the volume sampled for diagnostic procedures.Anaemia in neonates is strongly related to the amount of blood taken for diagnostic procedures. Alternatives for blood transfusions in premature infants, and consequently for the reduction of the number of donors per child, are to be sought in delayed clamping of the umbilical cord, use of erythropoietin and use ofautologous umbilical cord blood.

Although it has been long known that in theory the use of cholestyramine can cause coagulopathy due to reduced absorption of vitamin K, only a few cases have been reported. In those cases the coagulopathy occurred within a few weeks to months after the start of therapy. We report a patient with severe pruritus due to intrahepatic cholestasis, who was on cholestyramine therapy for over 25 years before haemorrhage occurred. This case demonstrates that one should be aware of the possibility of depletion of fat-soluble vitamins during the long-term use of cholestyramine.

Low density lipoprotein (LDL) increases the sensitivity of human platelets for agonists by activating p38MAPK. Antibody 4G3 disturbs apoB100 binding to the classical apoB/E receptor and inhibits LDL-induced p38MAPK activation, whereas an antibody against a distal domain on apoB 100 has no effect. Peptide RLTRKRGLKLA mimics the binding domain of apoB 100 called the B-site and activates platelet p38MAPK. Activation by B-site peptide is dose-dependent, transient and followed by desensitization, in accordance with receptor-mediated signalling. A scrambled peptide and a partially homologous peptide RKLRKRLLRDA mimicking the apoB/E receptor binding site of apoE in high density lipoprotein (HDL) also activate p38MAPK albeit 40% weaker, but an uncharged peptide lacks p38MAPK activating capacity. LDL and B-site peptide bind to the same binding sites and initiate similar signalling to p38MAPK and cytosolic phospholipase A2. Thus, LDL and to a lesser extent HDL activate platelets via specific domains in the protein moiety that recognize receptors of the LDL receptor family.

Abstract —LDL is known to increase the sensitivity of human platelets for agonists and to induce aggregation and secretion independently at high concentrations, but its mechanism of action is largely obscure. To clarify how LDL increases platelet sensitivity, cells were incubated in lipoprotein-poor plasma and treated with collagen at a concentration that induced ≈20% secretion of 14 C-serotonin. Preincubation with LDL (30 minutes at 37°C) enhanced secretion in a dose-dependent manner to 60±14% at a concentration of 2 g LDL protein/L. Similar stimulation by LDL was seen when secretion was induced by the thrombin receptor–activating peptide. This enhancement was strongly reduced (1) in the presence of monoclonal antibody PAC1 against activated α IIb β 3 , a polyclonal antibody against α IIb , and in the presence of the fibrinogen peptides GRGDS and HHLGGAKQAGDV; (2) in α IIb β 3 -deficient platelets; and (3) after dissociation of α IIb β 3 . In contrast, binding of 125 I-LDL to normal platelets in the presence of PAC1, anti-α IIb , GRGDS, and HHLGGAKQAGDV, and to α IIb β 3 -deficient platelets was normal. LDL increased the surface expression of fibrinogen in lipoprotein-poor plasma and fibrinogen-free medium, suggesting that extracellular and granular fibrinogen bind to α IIb β 3 after platelet-LDL interaction. Platelets deficient in fibrinogen (IIb β 3 preserved responsiveness to LDL, indicating that occupancy of α IIb β 3 was not restricted to fibrinogen. Inhibition of protein kinase C (bisindolylmaleimide) diminished fibrinogen binding and sensitization by LDL; inhibition of tyrosine kinases (herbimycin A) left fibrinogen binding unchanged but diminished sensitization by LDL. We conclude that an increased concentration of LDL, such as observed in homozygous familial hypercholesterolemia, sensitizes platelets to stimulation by collagen and thrombin receptor–activating peptide via ligand-induced outside-in signaling through integrin-α IIb β 3 .

Background. Dyslipidemia is found in the majority of renal and cardiac transplant recipients. Although 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors significantly lower low-density lipoprotein cholesterol (LDL-C) levels, such treatment has been associated with muscle toxicity, especially when used in combination with cyclosporine (CsA). We investigated the efficacy and muscle safety of fluvastatin, a new 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, in CsA-treated transplant recipients. Methods. The efficacy was determined by measuring the lipid profile before and after 8 weeks of fluvastatin therapy. As parameter for possible muscle damage, the rise in serum levels of the muscle proteins creatine kinase and myoglobin was measured after an exercise provocation test (30 min on a bicycle ergometer at 60% of their maximal work load) before and during fluvastatin therapy. Nineteen CsA-treated renal and cardiac transplant recipients with hypercholesterolemia were selected. Results. After 8 weeks of treatment with a dose of fluvastatin necessary to reduce LDL-C below 3.5 mmol/L (20 mg for 3 and 40 mg for 16 patients), total cholesterol was lowered by 20% and LDL-C by 30%, and HDL 2 -C was increased by 35% (all P

OBJECTIVE—To investigate whether administration of sodium fluoride (NaF) in addition to cyclical etidronate has a positive effect on bone mineral density (BMD) in patients with established osteoporosis during continued treatment with corticosteroids. PATIENTS AND METHODS—47 patients who were receiving treatment with corticosteroids were included in a two year randomised, double blind, placebo controlled trial. Established osteoporosis was defined as a history of a peripheral fracture or a vertebral deformity, or both, on a radiograph. All patients were treated with cyclical etidronate, calcium, and either NaF (25 twice daily) or placebo. Vitamin D was supplemented in the case of a low serum 25 (OH) vitamin D concentration. BMD of the lumbar spine and hips was measured at baseline and at 6, 12, 18, and 24 months. RESULTS—After two years of treatment, the BMD of the lumbar spine in the etidronate/NaF group had increased by +9.3% (95% confidence intervals (CI): +2.3% to +16.2%, p

Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.OBJECTIVE: Patients with familial combined hyperlipidemia (FCH) have an increased cardiovascular mortality despite only moderate elevations of LDL-cholesterol. Since endothelial NO release is intimately involved in the anti-atherosclerotic effects of the endothelium, we studied the effect of short-term lipid-lowering therapy on NO-mediated vasodilatation in patients with FCH. In view of only moderate LDL elevations, we evaluated whether alterations in other lipid fractions upon therapy correlated to changes in NO-mediated vasodilatation. METHODS: NO activity was assessed by serotonin-induced, nitric oxide-mediated increase in forearm blood flow (FBF). Measurements were performed 2 weeks off and 4 weeks on lipid-lowering therapy in 12 FCH patients using forearm venous occlusion plethysmography. Control experiments were performed in 12 healthy subjects. RESULTS: Serotonin-induced vasodilatation was impaired in FCH patients (FBF (unit ml/100 ml forearm tissue/min) from 3.0 (0.3) to 4.8 (0.4)) compared to controls (FBF from 2.9 (0.3) to 6.5 (0.6); p < 0.05 vs. FCH). FBF response to serotonin improved significantly upon lipid-lowering therapy (from 3.0 (0.3) to 5.7 (0.5); p < 0.05 treated vs. untreated). The level of improvement in endothelial function was significantly correlated to the absolute reduction of intermediate density lipoproteins upon lipid-lowering therapy (r = -0.64; p < 0.05), whereas it did not correlate to changes in VLDL- or LDL-cholesterol, nor to Lp(a). CONCLUSION: Patients with familial combined hyperlipidemia have impaired NO-mediated vasodilatation, that responds rapidly to lipid lowering medication, and may be related to changes in intermediate density lipoproteins.Publication Types: Clinical Trial

This study was designed to investigate whether methotrexate (MTX), used in the treatment of rheumatoid arthritis (RA), affects proliferation and differentiation of human osteoblasts in culture. The effects of MTX were assessed by analyzing markers of proliferation and differentiation of human trabecular bone-derived osteoblast-like cells cultured in the presence or absence of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Treatment of the osteoblastic cells with MTX resulted in a strong dose-dependent inhibition of cell proliferation with half maximal response at a dose of 30 nM. MTX did not interfere with cellular alkaline phosphatase (AP) activity, the number of cells expressing cytochemical AP, or basal osteocalcin production. Addition of 1,25(OH)2D3 to the cultures caused an enhanced AP expression and osteocalcin production coinciding with a decreased osteoblast proliferation. Coincubation of 1,25(OH)2D3 with MTX in doses > or = 100 nM further inhibited osteoblast growth and induced a significant stimulation of AP expression and activity, and production of osteocalcin above the values reached in the 1,25(OH)2D3 cultures. In conclusion, MTX proved to be a potent inhibitor of osteoblast proliferation but did not affect basal osteoblastic phenotypic expression. In the presence of the osteoblast differentiation-promoter, 1,25(OH)2D3, MTX further inhibited cell growth which was associated with enhanced AP activity and osteocalcin production. Thus, MTX may have profound effects on bone metabolism and remodeling by interfering with bone cell turnover.

We studied the effect of 2 mg micronized 17 beta-estradiol replacement therapy, administered orally during 6 weeks, on postprandial lipid and retinyl palmitate (RP) metabolism. In the human postprandial state, atherogenic chylomicron remnant particles are produced. RP is incorporated into the core of newly synthesized chylomicrons and can be used as a marker of chylomicrons and chylomicron remnants. Six normolipidemic (plasma cholesterol, 5.63 +/- 0.83 mmol/L; plasma triglycerides, 1.47 +/- 0.69 mmol/L) postmenopausal women (amenorrhea1 yr; aged 55.5 +/- 4.0 yr) received an oral fat load (50 g/m2 fat as cream, with 60,000 IU RP/m2) before and after 6 weeks of 17 beta-estradiol treatment. Plasma RP areas under the curve decreased significantly from 27.1 +/- 15.9 to 16.6 +/- 13.2 mg/h.L-1 (P = 0.01). Fasting cholesterol concentrations in intermediate density lipoproteins decreased significantly. Fasting and postprandial plasma triglyceride levels did not change. These findings indicated that 17 beta-estradiol improved the postprandial elimination of potentially atherogenic lipoprotein remnants.

The effect of corticosteroid pulse therapy on bone metabolism was studied in 10 patients with active RA. We measured alkaline phosphatase, osteocalcin and two recently introduced markers of collagen type 1 metabolism, reflecting synthesis (PICP) and degradation (ICTP). The day after the pulse therapy, there was a statistically significant (P < 0.05) decrease in osteocalcin, PICP and ICTP from the value at start. Three weeks after pulse therapy, these values had returned to baseline. During pulse treatment there is a transient decrease in bone formation, as shown by the changes in osteocalcin and PICP. Because of the changes in ICTP, we conclude that bone resorption is transiently reduced as well, but whether these changes result from a direct or an indirect effect on bone is not clear. ICTP has to be investigated further as a (serum) marker of bone resorption.

1. Potassium salts increase sodium excretion in humans. To define the role of the potassium ion in this effect, we compared the effects of equimolar single oral loads of 100 mmol of NaCl and KCl on renal electrolyte excretion in seven healthy subjects. In a second group (n = 7), we infused equimolar loads of NaCl or KCl (0.75 mmol/kg in 2 h). 2. In both experiments the KCl load quickly increased plasma potassium and aldosterone concentrations and potassium and sodium excretion to a maximum by 2 h after the load, whereas the NaCl load had no such effect. 3. In a third group (n = 7) we compared the effects of single oral loads of KCl and KHCO3 (1 mmol/kg), to assess the role of the anion in the natriuretic effect of potassium salts. 4. KCl and KHCO3 transiently stimulated urinary excretion of potassium and sodium in an identical manner. 5. We also followed the changes in acid excretion over time. Whereas both KCl and KHCO3 loading decreased acid excretion, this effect was greater after KHCO3 loading. Interestingly, acid excretion did not decrease further after the first collection hour after the potassium load, although the plasma potassium concentration was still increasing. 6. From these data we conclude (1) that increased excretion of sodium, potassium and chloride and decreased excretion of protons after administration of potassium salts are the specific effects of the potassium component; (2) that potassium also appears to have secondary, indirect effects on proton excretion, the mechanism of which remains to be clarified.

We present the oxalate excretion in two studies before and after intravenous infusion of diuretics in healthy subjects. One study was performed in 7 male subjects. An intravenous injection of 1 mg bumetanide was given, followed by intravenous infusion at a rate of 0.5 mg/h. A similar study was performed in 5 male subjects, who received an intravenous injection of 500 mg acetazolamide, followed by intravenous infusion at a rate of 250 mg/h. Urinary oxalate was measured by an enzymatic method

A spectrophotometric method for the simultaneous calculation of the concentrations of oxyhaemoglobin, methaemoglobin and bilirubin in cerebrospinal fluid is described, based on the first and second derivative spectrum between 350 and 650 nm. Specificity compares favourably with other methods currently in use. The proposed method minimises the effect of turbidity and permits the measurement of concentrations below 0–3 μmol/L.

The C-peptide increase after an oral glucose tolerance test (OGTT) and intravenous glucagon test (GT) was assessed to establish actual insulin dependency in 16 obese diabetic patients treated with insulin for years. The results, compared to five reference groups, showed two types of reaction: first, a negative response in 3 patients with a minimal C-peptide increase after either stimulation (range 0–0.1 ng/ml during GT, 0–0.5 during OGTT), not different from that in the insulin-dependent reference group (GT: 0.1 ± 0.2, OGTT: 0.1 ± 0.3. x¯ ± SD). Second, a positive response in 13 patients with a C-peptide increase, different from that in the insulin-dependent group after glucagon (range 0.7–5.6), and in 6 patients after OGTT (range 0.8–1.8). When insulin treatment was discontinued in two nonresponders, the B-hydroxybutyrate levels and ketobutyrate levels increased to over 2.1 and 0.60 mmol/L within 10 days, proving insulin dependency, and thus type I diabetes. B-hydroxybutyrate and ketobutyrate levels increased to maximal 0.4 and 0.17 after stopping insulin therapy in nine positive responders. No ketoacidosis developed during a 4-wk follow-up, indicating non-insulin dependency (type II diabetes). Measuring C-peptide after glucagon is a simple test that may be a discriminative method to establish insulin dependency in obese diabetic patients treated with insulin.

Summary: A critical evaluation of the determination of acid phosphatase of prostatic origin with the Du Pont ACA is reported. The affinity of the enzyme towards certain substrates, and the specificity of sodium thymolphthalein monophosphate as a substrate for prostatic acid phosphatase were investigated. The validity of this method, which is supposed to be specific for prostatic phosphatase is, however, limited; clinical data showed that related human acid phosphatases interfere and decrease the specificity of the determination.

Spectrophotometric assays for urinary metanephrines are still widely used because of the simple equipment needed. These methods, however, have the major drawback of being very susceptible to interference. Using the original Pisano technique (Pisano, J. J. (1960) Clin. Chim. Acta 5, 406-414) we have often observed overestimation of the metanephrine concentration. By measuring absorbances at three different wavelengths we were able to considerably reduce this positive bias. With many patients this resulted in a significant downward adjustment of the values found for the total metanephrine excretion.

Summary: Over a period of three years we determined haptoglobin levels by single radial immunodiffusion(RID) and the haptoglobin phenotype in over 1700 samples of patients suspected of a haemolytic disease.As haptoglobin phenotyping is rather laborious and therefore an expensive method, we re-evaluated thediagnostic need for phenotyping.From our reference values for the respective phenotypes of haptoglobin it may be theoretically argued thatphenotyping is still desirable when the RID value is in the range 400—1170 mg/1. Limiting ourselves tosuspected haemolytic diseases, one can abolish phenotyping beyond this narrow range without withdrawingimportant clinical Information. From the total group it appeared that 480 samples lay in this range. In 72samples (15% of 480) the evaluation of the RID values was essentially altered by phenotyping. Carefulexamination of the medical records indicated that in a number of cases laborious phenotyping had indeedcontributed to the diagnosis. Ist die Haptoglobin-Typisierung klinisch erforderlich fur eine zuverlassige Bestimmung von Haptoglobin mitder einfachen radialen Immunodiffusion?

Three different methods for the measurement of glycated haemoglobin or HbA1, based on agar gel electrophoresis, ion-exchange and affinity chromatography were compared. All three showed acceptable precision (overall CV being less than 5%) and correlated well with each other ( r> 0·945). The ion-exchange and affinity chromatography method proved to be independent of the amount of pre-HbA1cpresent. The electrophoresis method was independent of temperature in contrast to the other two methods, which shewed a strong and comparable temperature dependency. All three methods were dependent on the haemoglobin concentration and/or protein content of the haemolysate. Both ion-exchange and electrophoresis showed significant interference by changes in haemoglobin concentrations, whereas the protein concentration significantly biased the affinity chromatography figures. Taking into account their specific merits all three methods are acceptable for routine use.

C-peptide is a polypeptide originating from proinsulin after its cleavage in the B-cell. It is secreted equimolarly with the other cleavage product, insulin, into the portal circulation. Only a minimal fraction of C-peptide is extracted by the liver; it is supposed to be mainly removed by the kidney. A small, constant proportion is excreted in the urine. C-peptide is measured in serum and urine by radioimmunoassay. The major sources of error of the assay are related to standard, tracer, antiserum specificity and reactivity with proinsulin, and to degradation of C-peptide. Many secretagogues are used to evaluate the B-cell function, of which glucagon is the most simple. Clinical applications of C-peptide include differentiating between endogenous and exogenous hyperinsulinism and establishing the need of insulin therapy in diabetic patients already treated with insulin. The primary value of C-peptide, however, is in clinical research, where it offers a unique opportunity to follow the B-cell secretion in diabetic subjects and to evaluate the difference that various factors may exert on its activity.

In a controlled prospective trial, the effect of a switch from cellulose-based, low-flux dialysis membranes to polysulphone, high-flux membranes on lipid parameters was evaluated. Baseline values of lipid parameters were identical in the study group and the control group in which the dialysis membrane remained unchanged. After 6 wk, total triglyceride, very low-density lipoprotein (VLDL) triglyceride, and VLDL cholesterol decreased, respectively, 28 +/- 17 (P < 0.01), 38 +/- 17 (P < 0.01), and 24 +/- 21% (P < 0.05), and the proportion of total cholesterol that was high-density lipoprotein cholesterol increased from 15 +/- 5 to 18 +/- 5% (P < 0.05) in the high-flux polysulphone group, whereas these variables remained unchanged in the control group. Low-density lipoprotein and total cholesterol as well as Kt/V, protein catabolic rate, parathyroid hormone, albumin, and body weight did not change. No change in lipoprotein lipase activity was found. In a second study, the effects of a single hemodialysis session with high-flux polysulphone and low-flux, cellulose-based membranes on lipid parameters and lipolytic activity were compared in a cross-over fashion. Treatment with both membranes resulted in a significant decrease in plasma triglyceride, VLDL triglyceride, and VLDL cholesterol. Lipoprotein lipase activity increased during hemodialysis. Changes in lipid parameters and lipolytic activity were identical during the two treatments.

BACKGROUND Control of renal hemodynamics by the arterial baroreflex has never been proved in humans. Apart from the physiological viewpoint, this issue is relevant because altered baroreflex function has been implicated in the pathogenesis of human hypertension. METHODS AND RESULTS Renal function studies were performed in seated healthy volunteers (n = 12; age range, 20 to 34 years) during sustained neck suction at -60 mm Hg, aiming to selectively activate the carotid sinus arterial baroreceptors. Two protocols were followed. One group of 6 volunteers taking a 20 mmol/d sodium diet underwent 90 minutes of neck suction. Compared with a time-control study, neck suction decreased arterial pressure and heart rate; increased glomerular filtration rate (inulin clearance) from 104 +/- 6 to 114 +/- 8 mL/min (P < .01), renal plasma flow (para-aminohippurate clearance) from 616 +/- 52 to 665 +/- 42 mL/min (P < .01), and renal blood flow (from 1120 +/- 95 to 1209 +/- 77 mL/min, P < .01); and decreased renal vascular resistance (from 86 +/- 8 to 76 +/- 6 mm Hg.min.L-1, P < .01). Neck suction had no effect on plasma renin activity, aldosterone, atrial natriuretic peptide, catecholamines, and renal sodium excretion. The other 6 volunteers took a normal sodium diet and underwent sustained neck suction for 60 minutes. In this group, no effects on renal hemodynamics could be discerned, despite a modest decrease in blood pressure and heart rate. CONCLUSIONS These data show, for the first time, that the arterial baroreflex is involved in the control of renal hemodynamics in humans. However, basal arterial baroreflex control of renal hemodynamics is probably low, and arterial baroreflex activation with subsequent renal vasorelaxation may be found only in conditions in which basal arterial baroreflex control of kidney function is significant, as is presumably the case in seated sodium-restricted subjects.

Unexpected uptake of 99mTc-phosphate by a neuroblastoma in a 36-year-old woman is described. Awareness of this phenomenon can be helpful in establishing the diagnosis.