Renal 131I-hippurate clearance overestimates true renal blood flow in the instrumented conscious dog.

We evaluated renal 131I-hippurate clearance (ERPFhip) as a measure of renal blood flow (RBF) in chronically instrumented conscious dogs. When adjusted for renal hippurate extraction (Ehip, 0.77 +/- 0.01) and hematocrit (Hct, 39.7 +/- 1%), calculated RBFhip (656 +/- 37 ml/min) markedly exceeded renal blood flow measured with renal artery blood flow probes (RBFprobe, 433 +/- 27 ml/min). The discrepancy could not be explained by flow probe calibration, because in vivo comparison of flow probe values with renal venous outflow showed only a slight underestimation of renal blood flow (slope 0.93, 95% confidence interval 0.89-0.97). Redistribution of hippurate from erythrocytes into renal venous plasma during or shortly after blood sampling led to an underestimation of Ehip by 4 +/- 1% and thus could only explain a small part of the difference. Extrarenal hippurate clearance was excluded, because the amount of 131I-hippurate cleared from plasma equaled that appearing in the urine (303 +/- 17 and 307 +/- 17 ml/min). Applying these corrections, we found that RBFhip still exceeded RBFprobe by 37 +/- 3%. These data indicate that renal blood flow measured by the hippurate clearance technique markedly overestimates true renal blood flow. Because other errors were excluded, a combination of sampling of nonrenal blood and intrarenal hippurate extraction from erythrocytes might play a role.

Iodine-131 Hippuran for the estimation of renal plasma flow: requirements for radiochemical purity.

For many years iodide-131 Hippuran has been used as a tracer to measure effective renal plasma flow (ERPF). Because of the low renal clearance of free 131I-iodide and the inability to count it separately from 131I-Hippuran, free 131I-iodide will lower the calculated 131I-Hippuran clearance, resulting in a lower estimated ER-PF. This study was performed to establish the maximum allowable radiochemical impurity of free 131I-iodide in 131I-Hippuran preparations for ERPF measurements in continuous clearance studies. A known amount of 123I-iodide was added to the (131I-iodide-free) 131I-Hippuran solution used for continuous infusion clearance studies in nine patients. 123I-iodide activity was used because it can be counted separately from 131I-Hippuran in the infusion solutions and plasma samples while it behaves exactly like 131I-iodide, so that the results obtained with 123I-iodide can be extrapolated to 131I-iodide. After performing the clearance studies, the ERPF was calculated firstly with 131I-Hippuran activity only (= true ERPF) and secondly including the free radioactive iodide activity (= false ERPF) in the clearance formula. As expected, if free 131I-iodide is present in the infusion solution, its concentration in plasma will be highest at the end of the clearance study. The 131I-iodide concentration in plasma relative to the 131I-Hippuran concentration will be higher in patients with high ERPF values.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of short-term and long-term treatment with inhaled corticosteroids on bone metabolism in patients with airways obstruction. Dutch CNSLD Study Group.

BACKGROUND: Recent reports have suggested short-term changes in serum parameters of bone metabolism with inhaled corticosteroids. The relevance of these findings to the balance between bone formation and resorption during years of corticosteroid treatment remains uncertain. METHODS: Two novel markers of bone turnover were first compared with conventional markers in a pilot study and subsequently measured in a long-term double blind study of inhaled corticosteroids. In study I 15 patients were newly started on at least 800 micrograms inhaled corticosteroids daily. At entry and after four weeks serum levels of alkaline phosphatase, osteocalcin, and PICP (procollagen type I carboxy terminal propeptide; a procollagen splice product) were measured as markers of bone formation, as well as the urinary hydroxyproline/creatinine ratio and serum levels of ICTP (type I collagen carboxy terminal telopeptide; a collagen degradation product) as markers of bone resorption. In study II 70 patients with airways obstruction received 800 micrograms beclomethasone daily in addition to terbutaline and 85 received bronchodilators only in a double blind fashion. Serum levels of PICP and ICTP were measured before and after 2.5 years of treatment. RESULTS: In study I a decrease in osteocalcin levels was accompanied by an increase in levels of PICP and a small and non-significant rise in alkaline phosphatase. There were no changes in hydroxyproline or ICTP. In study II no differences were found in serum levels of PICP between the treatment groups; an increase in serum ICTP was found in the group treated without inhaled corticosteroids compared with the group treated with inhaled corticosteroids. CONCLUSIONS: No detrimental long-term effect of inhaled corticosteroids was found with three conventional and two novel parameters of bone metabolism. The results indicate that long-term changes in bone turnover during treatment with inhaled corticosteroids should not be deduced from short-term studies with single serum parameters of bone metabolism, but well designed long-term studies of, for example, bone densitometry should be awaited before quoting detrimental effects of inhaled corticosteroids on bone metabolism.

Expression and regulation of IL-4 receptors on human monocytes and acute myeloblastic leukemic cells.

Evidence is presented that human monocytes and acute myeloblastic leukemic (AML) cells contain both high and low affinity binding sites for interleukin-4 (IL-4). On monocytes 183 +/- 132 high affinity binding sites per cell with a Kd of 60 +/- 29 pM and 1500 +/- 600 low affinity receptors with a Kd of 2.3 +/- 0.4 nM (X +/- S.D., n = 6) could be demonstrated. On AML cells (n = 11) a comparable number and binding affinity of IL-4 receptors were observed (77 +/- 36 high affinity receptors with Kd 72 +/- 31 pM and 2400 +/- 1000 low affinity receptors with Kd of 2.2 +/- 0.7 nM). In addition, no cross-competition was shown between radiolabeled IL-4 and IL-1-alpha, IL-3, IL-6, IL-7, G-CSF, and GM-CSF. Both types of receptors on monocytes as well as on leukemic blasts could be down-modulated in a similar fashion by IL-4 and activators of protein kinase C (PKC), but not by the calcium ionophore A23187. The down-modulation by PKC activators was caused by an increased internalization, degradation and release of radiolabeled IL-4 in the medium. Finally, the functionality of the IL-4 receptors were tested on AML cells with a 3H-thymidine proliferation assay. In 8/11 cases IL-4 affected AML proliferation. These data demonstrate two different binding sites for IL-4 on normal and leukemic cells, which can be modulated by external activation signals in an analogous way.

Prostatic acid phosphatase: comparison of radioimmunoassay and enzyme activity assay.

Aspects of the clinical use of an enzymatic assay and a double antibody radioimmunoassay for prostatic acid phosphatase are compared. Standard blood sample collection and transport did not have a negative effect on the results of either assay. Our results show no substantial advantage in the use of a radioimmunoassay but emphasize the reliability of the enzymatic assay using alpha-naphthylphosphate as a substrate with respect to its predictive value and specificity in diagnosis and followup of patients with prostatic carcinoma.

The significance of the aminoterminal propeptide of type III procollagen in paroxysmal nocturnal haemoglobinuria and myelofibrosis.

The level of the aminoterminal propeptide Col 1-3 of type III procollagen (PC-III) was determined in patients with paroxysmal nocturnal haemoglobinuria (PNH) and primary myelofibrosis (PMF), to study whether PC-III can be used as a parameter for the rate and/or degree of bone marrow replacement with collagen. Normal PC-III levels were found in PNH (6.6 +/- 1.1 micrograms/l; N: 8.6 +/- 1.8 micrograms/l), while significantly increased levels were found in PMF (24.8 +/- 2.2 micrograms/l). During a follow-up of 1 year, a slight increase of 2 micrograms/l occurred in three patients with a stable fibrosis, while one patient with more active disease demonstrated an increase of 25 micrograms/l. Treatment with acetylsalicylic acid led to a decline of PC-III as well as beta-thromboglobulin level, although normalization did not occur. It was demonstrated by means of gel filtration that the antigens related to the PC-III peptide were heterogenous, and that in PMF at least two main peaks were present, with molecular masses equal to and smaller than PC-III peptide. These data demonstrate that the radioimmunoassay cannot be used for the quantitative determination of PC-III; nevertheless it gives some insight in the process of bone marrow fibrosis.

The effect of cold-induced brain edema on cerebrospinal fluid formation rate.

The net contribution of vasogenic brain edema to cerebrospinal fluid (CSF) formation was studied by ventriculocisternal perfusion. Individual cats were perfused both before and 2 1/2 hours after a severe cold-induced injury to the cerebral cortex, and the results were compared. Although the edema had occupied the larger part of the hemispheric white matter and bordered the lateral ventricle, a decrease rather than an increase in CSF formation rate was observed. This decrease was related to a decrease in the cerebral perfusion pressure by a regression equation that was not affected by the cold injury.

The effect of intracerebral ouabain administration on the composition of edema fluid isolated from cats with cold-induced brain edema.

Brain edema fluid was collected from cats with a freezing lesion in the left parietal cortex by the insertion into the brain of needles containing nylon wicks and connected to polyethylene tubes. The edema fluid samples which accumulated in the polyethylene tubes were regularly analyzed for Na+ and K+ content, colloid osmotic pressure, lactate dehydrogenase and creatine phosphokinase activity, and 99mTc-albumin radioactivity; the albumin tracer being introduced intravenously at the time of cold-injury. One series of cats received an intracerebral injection of ouabain solution, the control series an intracerebral injection of saline, at 100 min after the cold-injury. The ouabain injection was followed by an increase of K+ content, LDH and CPK activities but a decrease of Na+ concentration in the edema fluid, attributable to a concentration of solutes in the edema fluid as presumably water and Na+ were shifted into the cells and hence the extracellular space was reduced.

Composition of isolated edema fluid in cold-induced brain edema.

Edema fluid isolated from cats with cold-induced brain edema was subjected to analysis of electrolyte content, enzyme activities, colloid osmotic pressure and the radioactivity of intravenously injected 99mTc-labeled albumin. The findings corroborate the essential features of vasogenic edema, such as its origin from the blood plasma, its rapid propagation into the white matter of the brain as contrasted with the delayed spread into gray matter, and its contribution to composition of cerebrospinal fluid. Moreover, the elevated activities of cellular enzymes and K+ content of edema fluid point to the admixture with cellular contents due to the freezing damage.

Influence of hypoxia on the composition of isolated edema fluid in cold-induced brain edema.

The isolation of edema fluid from cats with cold-induced cerebral edema allowed the study of changes of Na+ and K+ content, lactate dehydrogenase and creatine phosphokinase activity, colloid osmotic pressure and the level of intravenously administered 99mTc-albumin in the edema fluid during a period of hypoxia. The changes consisted of an increase of all mentioned parameters, except Na+; and could be interpreted as a concentration of solutes (but for Na+) in the extracellular edema fluid, concomitant to a reduction of the extracellular space, as the oxygen deficiency caused improper functioning of the cellular Na+-K+ pump, with a resulting shift of fluid (including Na+) into the cellular elements.

TRH by slow, continuous infusion: an antidepressant?

A slow, continuous infusion of 1000 mug TRH (thyrotropin releasing hormone) over a period of 4 h had a very faint and diffuse short-lasting beneficial effect on a group of 10 depressive patients. This was assessed in a double blind cross-over trial with placebo. The effect was of no therapeutic value. No difference was found between the depressive patients and a control group of normal subjects in TSH response, T3 resin uptake, T4 or free thyroxine index values as a consequence of the TRH infusion.

Serial human placental lactogen estimations in serum and placental weight-for-dates.

The relation between serial HPL assays in serum and placental weight-for-dates was studied in 70 randomly chosen pregnant women. Out of five different aspects of the HPL curve only a fall below the 2-3d centile without subsequent recovery was related to low placental weight. When a small-for-dates (SFD) placenta was associated with normal HPL levels, maternal body weight tended to be lower than if both placental weight and HPL levels were abnormal. This suggests that physiologically small placentae are discernible from pathologically small placentae by a normal HPL curve.

Thyrotropin releasing hormone (TRH) as a possible quick-acting but short-lasting antidepressant.

In a double reversal design the potency of thyrotropin releasing hormone (TRH) (500 mug intravenously) as a quick-acting antidepressive agent was evaluated. A first injection did seem to give rise to a very slight short-lasting effect, though this could not be ascertained clearly. There were no visible effects after a second injection. The thyroid stimulating hormone (TSH) response curve after TRH administration in the depressive patients group was blunted in comparison with that in a matched control group of normals.