O. Schober

Results of a stimulatory therapy of low bone metabolism in osteoporosis with (1-38)hPTH and diphosphonate EHDP. Protocol of study I, osteoporosis trial Hannover.

SummaryIn contrast to prevention, the therapy of manifest osteoporosis remains a clinically significant problem. So far all therapeutic attempts have yielded unsatisfying results. For this reason we have tried to achieve a positive bone balance by sequential stimulation and inhibition of the osseous metabolism. The therapy consisted of six 14-day courses with 400 units (1–38)hPTH per day and, in addition, starting with the 2nd week of PTH therapy, EHDP 5 mg per kg body weight per day for a total of 2 weeks. Already the initial therapeutic course resulted in a stimulation of decreased bone metabolism which could be documented by an increase in the calcium-47 accretion rate (six patients). An increase of the alkaline phosphatase could be noted (four patients); this, however, did not correlate with the calcium accretion. A positive calcium balance could, nonetheless, only be attained in four of eight patients within this period, while neither the alkaline phosphatase nor the kinetics would allow a prediction of this effect. Changes of the balance coincided with equal changes in the net calcium absorption. The urinary calcium excretion increased temporarily during the therapeutic phase. We were not able to detect an influence on the vitamin D metabolites. Histomorphometric studies did not demonstrate an increase in bone mass in the iliac creast after six therapeutic courses. Nevertheless, progressive deformations of vertebral bodies did not occur. We conclude that already after 2 weeks this therapeutic concept can lead to a stimulation of bone metabolism.

Non selective transport of [11C-methyl]-L-and D-methionine into a malignant glioma

Images obtained by X-ray CT, brain scintigraphy (99mTc-DTPA) and positron emission tomography (PET) with [11C-methyl]-L- and D-methionine in a case of malignant glioma are presented, showing good agreement of PET and CT findings, in particular nearly identical localization of L- and D-methionine accumulation, whereas the blood brain barrier is only slightly disturbed. In a greater number of patients the amount of accumulated stereoisomers do not differ on a significant level, indicating that a raised transport rate mediated by a carrier of low stereospecifity seems to contribute substantially to the increased uptake of [11C-methyl]-L-methionine in human brain tumors. Several cerebral functions and diseases have been studied with positron emission tomography (PET), which represents a clinical tool for visualizing metabolic activities rather than morphologic lesions (Reivich et al. 1985; Mazziotta et al. 1986). With regard to the malignancy of brain tumors DiChiro et al. (1982, 1984, 1985 a, b) showed a correlation between tumor grade and its glucose metabolism measured with 18F-fluorodeoxyglucose. An increased uptake of [11C-methyl]-L-methionine into tumor tissue has also been described (Hübner et al. 1980; Bergström et al. 1983; Kubota et al. 1984; Meyer et al. 1985; Schober et al. 1986b). Bustany et al. (1981, 1983, 1985a, b, 1986) developed a model for quantitative determination of protein synthesis, postulating that methionine incorporation into protein in brain tumors correlates with grade of malignancy. We do not believe that the uptake of [11C-methyl]-L-methionine mainly reflects protein synthesis, because [11C-methyl]-D-methionine is accumulated in normal brain tissue and intracranial tumors in nearly the same manner as [11C-methyl]-L-methionine, the physiological substrate for protein synthesizing enzymes (Meyer et al. 1985). The following case report illustrates these findings.

Uptake of 11C-L- and D-methionine in brain tumors

Abstract11C-labeled l-and d-methionine uptake was measured in seven patients with brain tumors using positron emission tomography. Tumors accumulated both isomers of the tracer. The strongest uptake occurred in tumors with a high grade of malignancy, while low grade tumors accumulated less activity. The l to d uptake ratio in tumor regions ranged from 0.92–1.25. Conventional 99mTc-DTPA scans revealed blood-brain barrier damage in two patients with no or only slight 11C-methionine accumulation, while one patient with a negative 99mTc-DTPA scan accumulated 11C-methionine in the tumor region. In view of the biochemical pathway of methionine and the present findings, it is concluded that the uptake reflects metabolic activity in brain tissue rather than uptake by diffusion due to disruption of the blood-brain barrier.

Quantification of regional extravascular lung water in dogs with positron emission tomography, using constant infusion of 15O-labeled water

Continuous infusion of 15O-labeled water allows a quantitative measurement of the total water pool in the chest region by positron emission tomography (PET). By subsequent inhalation of 11CO the intravascular space (blood pool) can be quantitated as well. After a suitable normalization of the intravascular activities the extravascular water can be determined by subtraction of the blood pool from the water pool. The regional extravascular lung water distribution can be visualized in tomographic slices. The method was validated in an animal experiment using five dogs. They were measured before and after induction of a lung edema by IV injection of oleic acid. The increase of extravascular lung water was monitored by the thermodye-dilution method (TDD). The correlation of extravascular lung water as measured by TDD with PET measurements is good (r=0.94). The PET values agree also with gravimetric lung water determinations. An absolute quantitation of regional extravascular lung water is possible after absorption correction of the PET data via transmission measurements and calibration of the camera system. The uncertainty in the absolute quantification is±20%. In the experiments described here the mean extravascular lung water was 0.13 g/cm3 before and 0.25 g/cm3 after induction of lung edema.

Total body water, extracellular water, plasma volume, and total body potassium in cirrhosis of the liver

ZusammenfassungUntersucht wurden die Flüssigkeitsräume Extrazellulärwasser (82-Bromid; ECW), Ganzkörperwasser (3-THO; TBW), Intrazellulärwasser (ICW=TBW-ECW) und Plasmavolumen (51-Chrom; PV), sowie das Ganzkörperkalium (40-K; TBK) bei Lebercirrhotikern (n=12) im Vergleich zu einer Kontrollgruppe (n=12). Die auf das Körpergewicht bezogenen Größen ECW (39%), TBW (28%), ICW (19%) und PV (24%) fanden wir bei den an Lebercirrhose Erkrankten vergrößert, das Ganzkörperkalium (% des Sollwertes) um 28% erniedrigt. Diese Ergebnisse weisen darauf hin, daß bei der Lebercirrhose weniger die sogenannte fettfreie Substanz (lean body mass; LBM) als vielmehr die intrazelluläre Kaliumkonzentration verringert ist. (Cirrhose: 84±21 mol/l ICW; Kontrolle: 115±23 mmol/l ICW). Als Ursachen werden ein vermindertes Kalium (mmol) pro Zelle und eine vergrößerte intrazelluläre Wasserkonzentration (ml/kg) diskutiert. Die Korrelation zwischen dem TBK (%) und dem Serum-Kalium (mmol/l) beträgtr=0,56 (p<0,002). Die klinisch chemischen Parameter γ-Globuline, Cholinesterase, Serumnatrium und Albumine (g/l PV) korrelieren signifikant mit den charakteristischen Veränderungen der Flüssigkeitsräume und des Ganzkörperkaliums. Hierbei ist das auf das Körpergewicht bezogene Gesamtalbumin trotz der relativen Hypoalbuminämie nicht erniedrigt. Unsere Ergebnisse sprechen für die ‘overflow theory’ der Ascites-Pathogenese (Lieberman et al., 1970).SummaryExtracellular water (EWC; 82-bromide), total body water (TBW; 3-THO), intracellular water (ICW=TBW-ECW), plasma volume (PV; 51-Cr), and total body potassium (TBK; 40-K) were studied in patients with cirrhosis of the liver (n=12) and in controls (n=12). ECW (39%), TBW (28%), ICW (19%), and PV (24%) increased, TBK (28%) however, decreased in cirrhosis. The results indicate that it is less the lean body mass, but rather the intracellular potassium concentration that is lowered (cirrhosis: 84±21 mmol/l ICW; controls: 115±23 mmol/l ICW). Decreased potassium per cell (mmol) and increased intracellular water are discussed as possible reasons for this. The correlation between TBK (%) and serum potassium (mmol/l) was found to ber=0.56 (p<0.002). Correlations between the biochemical parameters gamma-globulins, cholin esterase, serum sodium and serum albumin (g/l PV) and characteristic fluid disturbances in cirrhosis are highly significant whereas albumin (g/kg bodyweight) was the same in both groups. We can support the ‘overflow theory’ of ascites formation [19].

Bromide space, total body water, and sick cell syndrome

Displacements of the bromide space (Br-82-C, as a marker for the extracellular fluid compartment) are caused by an enhanced anatomical space and/or increased permeability of cells to bromide. The ratio Br-82-C: total body water (TBW) was evaluated to be 0.83±0.17 in critically ill patients (n=38) compared with the normal value of 0.46±0.04 (n=10). Because of normal TBW in critically ill patients (TBW=505±68 ml/kg), an increased bromide penetration into cells seems to be responsible for the enlarged ratio Br-82-C: TBW. Taking into consideration measurements in patients with malabsorption (Br-82-C: TBW=0.56±0.13; n=13) and carcinoma of the rectum and colon (Br-82-C: TBW=0.66±0.24; n=18) we think that the bromide space is a good measurement of the effective extracellular water.

A whole body counter with an invariant response for whole body analysis.

A scanning 6-detector whole body counter is described. Its characteristics include good sensitivity, high energy resolution, good counting efficiency, geometric uniformity and localisation information of incorporated radioactivity using collimators. Problems such as band-width, calibration for air and phantom and measurements on patients, are discussed. The whole body counter is compared to other systems.

Evaluation of linear profile scans; mathematical treatment of line-spread functions

The profile measurement capability of a scanning multidetector whole-body counter is described using line spread functions. Measurements in air and water phantoms, as a function of energy, are discussed in relationship to the relevant physical processes. A computer program for evaluating bodyprofile scans and an attempt to improve the resolution are reported.

Altered potassium homeostasis in Crohn's disease

The total body potassium (TBK), serum potassium, and the number of red blood cell ouabain-binding sites was studied in 94 patients with Crohns disease. TBK was measured by counting the endogenous 40K in a whole body counter. TBK was 87%±13% in 94 patients with Crohns disease, while in control subjects, it was 97%±12% (n=24). This significant reduction in TBK was accompanied by normal serum potassium levels (4.4±0.5 mM). TBK was significantly correlated with the Crohns disease activity index (r=0.79, n=113, P<0.01). The number of red cell ouabain binding sites measured by equilibrium binding of 3H-ouabain showed a significant increase in the number of Na−K pumps in Crohns disease (396±65, n=27) compared with the control group (290±45; n=24). These results support the suggestion that changes in TBK may regulate the synthesis of Na−K pump molecules. The total body potassium depletion and the need for a preoperative nutritional support in Crohns disease are discussed.

Amino Acid Metabolism in Brain Tumors

Positron emission tomography (Pet) has become the most sophisticated method for studying regional metabolic functions of the brain (PHELPS 1986; REIVICH and ALAVI 1986). While blood flow, glucose consumption, and receptor densities are all highly structured, with active centers in normal and in pathological conditions, other functions, like oxygen extraction and protein synthesis, show a more uniform distribution in normal physiological situations (Frackowiak and Lammertsma 1985). However, oxygen extraction is a high level process in brain tissue, whereas protein synthesis is low in normal brain. Therefore increased protein synthesis in pathological states may be an ideal indicator, with high contrast for abnormally growing tissue in the brain.