Labelling of leucocytes with colloidal tech netium-99m-SnF2: an investigation of the labelling process by autoradiography

Autoradiography of smears and frozen sections of labelled cell suspensions was used to study the distribution of radioactivity in and among blood cells labelled in either whole blood or leucocyte-rich plasma (LRP) with technetium-99m-SnF₂ colloid. The tracer proved selective for neutrophils: the labelling probability (relative to that for erythrocytes) for each cell type in LRP (mean of five samples) was: neutrophils, 9.4; lymphocytes, 3.7; monocytes, 3.0; eosinophils 1.4; erythrocytes, 1.0. When labelling was carried out in whole blood (five samples), 74.5%±8.3% of the cell-bound radioactivity was bound to erythrocytes, 13.6%±6.5% to neutrophils, and 11.9%±2.1% to lymphocytes, whereas in LRP (in which the leucocytes were only slightly out-numbered by erythrocytes), 76.5%±14.9% of radioactivity was neutrophil bound. Labelled cells in smear autoradiographs exhibited two distinct silver grain patterns, diffuse, consistent with an intracellular radioactive particle (in neutrophils), and focal, consistent with a cell surface-adhering particle in direct contact with the emulsion (in other leucocyte types and erythrocytes). The phagocytic inhibitor cytochalasin B neither reduced the proportion of labelled neutrophils nor altered the labelling pattern. Neutrophils were able to scavenge radioactivity from the surface of erythrocytes. It is concluded that neutrophils bind^99mTc-SnF₂ intracellularly by phagocytosis, with high affinity; other cells become labelled at the cell surface reversibly and with lower affinity. This selectivity is high enough to permit predominantly leucocyte labelling in LRP but not in whole blood.     

Evaluation of delta-aminolaevulinic acid excretion in random urine samples of children

Urinary delta-aminolaevulinic acid (-ALA) excretion was evaluated in random urine samples of 191 healthy children, aged 2–14 years, with blood lead levels <0.8 mol/l (mean ± SD: 0.34±0.13), erythrocyte zinc-protoporphyrin <70 mol/mol haem (mean ± SD: 50.4±8.0) and blood haemoglobin >6.8 mmol/l (mean ± SD: 8.2±0.5). It was found that uncorrected -ALA concentration and -ALA/creatinine ratio are age-dependent, whereas the ratio of -ALA/logarithm of creatinine concentration (mean ± SD: 55.3±13.5 mol/log mmol) is independent of age and sex. The authors recommend the use of this parameter for the assessment of -ALA excretion in random urine samples in children     

MR imaging of the male pelvis

Prostate and urinary bladder cancer are the most frequently encountered malignancies of the urinary tract. Appropriate use of the different imaging techniques is crucial for accurate assessment of prognosis and for the development of appropriate treatment planning. Especially determination of local tumor extension and detection of nodal or bone metastases is extremely important. In this regard MR imaging is the most promising imaging technique. Therefore, in this review its role in staging these malignancies is evaluated and compared with clinical staging, and other imaging techniques. Finally, future developments, such as new sequences, new contrast agents, the role of surface coils and MR-guided biopsy, are considered. Also, the preferred radiological approach is discussed.     

Iodine deficiency disorders in Bangladesh

An extensive iodine deficiency disorders survery was conducted in Bangladesh in 1993 to assess the latest iodine nutriture status of the country. The clinical variables of the survey were goitre and cretinism, and the biochemical variable was urinary iodine. The “EPI-30 cluster” sampling methodology was followed for selecting the survey sites. In each survey site, the study population consisted of boys and girls, aged 5–11 years, and men and women, aged 15–44 years, in about equal populations. the total number of survey sites was 78 and the total number of respondents was 30 072. The total number of urine samples was 4512 (15% sub-sample). The current total goitre rate (grade 1+grade 2) in Bangladesh is 47.1% (hilly, 44.4%; flood-prone, 50.7%; and plains, 45.6%). The prevalence of cretinism in the country is 0.5% (hilly, 0.8%; flood-prone, 0.5%; and plains, 0.3%). Nearly 69% of Bangladeshi population have biochemical iodine deficiency (urinary iodine excretion [UIE]<10 mg/dl) (hilly, 84.4; flood-prone, 67.1%; and plains 60.4%). Women and children are more affected than men, in terms of both goitre prevalence and UIE. The widespread severe iodine deficiency in all ecological zones indicates that the country as a whole is an iodine-deficient region. Important recommendations of global interest are made from the experience of the survey. An erratum to this article is available at .     

Different behaviour of radioiodinated human recombinant interleukin-1 and its receptor antagonist in an animal model of infection

Recently, we demonstrated that radiolabelled interleukin-l (IL-1) specifically accumulates in focal infection in mice through interaction with its receptor. Unfortunately, systemic side-effects of IL-1 limit its clinical application. We investigated whether this problem could be circumvented by using the interleukin-1 receptor antagonist (IL-Ira), an equally sized protein that binds to the same receptors as IL-1 without induction of biological effects. Biodistribution of¹²⁵I-IL-1 and¹²⁵I-IL-Ira was determined in Swiss mice withStaphylococcus aureus-induced abscesses in the left calf muscle at 4, 12, 24 and 48 h after injection of either 0.4 MBq¹²⁵I-IL1 or 0.4 MBq¹²⁵I-IL-Ira. In vitro, the proteins displayed similar binding characteristics. High-performance liquid chromatographic analysis revealed a tendency for IL-Ira to associate with serum proteins. Both proteins rapidly cleared from most organs. However, the abscess uptake of¹²⁵I-IL-Ira was significantly lower than that of¹²⁵I-IL-1 at all time points (48 h p.i.: 0.06±0.01%ID/g vs 0.60±0.04%ID/g;P<0.02). The abscess-to-contralateral muscle ratios did not exceed 15.5±2.9 for¹²⁵I-IL-lra, while the ratios for¹²⁵I-IL-1 reached 46.9±5.7 at 48 h p.i. Despite similar in vitro receptor binding, the abscess uptake of IL-Ira was much lower than that of IL-1. The interaction of IL-Ira with serum proteins in vivo may reduce its availability for receptor binding in the infection. Although on theoretical grounds IL-Ira is very interesting, these characteristics will prevent its development as a clinically useful radiopharmaceutical to image infection.     

Double β-lactam regimen compared to an aminoglycoside/β-lactam regimen as empiric antibiotic therapy for febrile granulocytopenic cancer patients

In a prospective, randomized trial, 205 febrile episodes in granulocytopenic cancer patients were treated with ceftazidime with or without tobramycin (C±T), both agents being administered only if the initial granulocyte count was below 200/l, or ceftazidime plus piperacillin (C+P). The overall response rate was 71% (39 of 60 for C±T and 45 of 58 for C+P). Logistic regression analyses documented no evidence of a significant difference between the two regimens in overall treatment effect after accounting for the linear effects of potentially important variables, such as infection type and granulocyte count. Although the response rates for the subgroup of patients with bacteremias was better with the C+P regimen (P=0.06), there was no difference in response for patients with bacteremia and profound (<100/gml) sustained granulocytopenia. The double -lactam combination demonstrated in vitro synergism in 73%; antagonism was not seen. Both regimens produced execllent serum bactericidal levels (C±T geometric mean peak 1:170; C+P peak 1:137) against gram-negative but not gram-positive pathogens (1:4; 1:7 respectively) that had caused bacteremia. Emergence of resistance and significant coagulopathy and/or bleeding did not occur during therapy. Antibiotic-related nephrotoxicity was noted in 7 of 95 trials in the C+P and in 6 of 89 trials in the C±T group (P=0.19). The incidence of secondary infections in patients with profound (<100/l) sustained granulocytopenia was lower in the C±T group (P=0.04). Alimentary canal anaerobic flora preservation with C±T, and suppression with C+P, was demonstrated. These results suggest that these regimens are of similar effectiveness and neigher is associated with major toxicity.     

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the in vivo and in vitro dechlorination of pentachlorophenol

The metabolism of pentachlorophenol has been studied in the rat after pretreatments with phenobarbital, 3-methyl-cholanthrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In addition to the previously identified metabolite, tetrachloro-p-hydroquinone, trichloro-p-hydroquinone has been identified in urine as a metabolite. The formation of the latter represents a type of dechlorination different from that of the formation of tetrachlorohydroquinone. The inducing agents, 3-methylcholanthrene and TCDD have similar effects on the dechlorination and increase the formation of tetrachloro-p-hydroquinone more pronounced than does phenobarbital. In contrast to phenobarbital they also increase the formation of trichloro-p-hydroquinone and the total elimination of pentachlorophenol and its metabolites. The in vivo findings are supported by in vitro studies with microsomes from rats pretreated with phenobarbital or TCDD. Use of the inhibitor -diethylaminoethyl-diphenyl propylacetate (SKF 525-A) in vitro showed a more pronounced inhibition on microsomes from phenobarbital-treated rats than on microsomes from untreated or TCDD-treated rats.Gas chromatography-mass spectrometry have been used for the identification and quantification of pentachlorophenol and its metabolites.

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Zusammenfassung Der Metabolismus von Pentachlorphenol nach Vorbehandlung der Versuchstiere (Ratten) mit phenobarbital, 3-Methylcholantren oder 2,3,7,8-Tetrachlordibenzo-p-Dioxin (TCDD) ist untersucht worden. Zu dem schon früher nachgewiesenen Metaboliten Tetrachlor-p-Hydrochinon wurde nun auch Trichlor-p-Hydrochinon als Harnmetabolit festgestellt. Die Bildung des letzteren stellt eine andere Art von Dechlorierung dar als diejenige die bei der Entstehung von Tetrachlor-p-Hydrochinon vorliegt. 3-Methylcholantren und TCDD haben ähnlichen Einfluß auf die Dechlorierung und steigern die Bildung von Tetrachlor-p-Hydrochinon mehr ausgeprägt als es bei phenobarbital der Fall ist. Im Gegensatz zu phenobarbital steigern sie auch die Bildung von Tri-chlor-p-Hydrochinon sowie die totale Eliminierung von Pentachlorphenol und von Metaboliten. Die in vivo-Befunde werden von in vitro-Studien mit Mikrosomen von mit phenobarbital oder TCDD vorbehandelten Ratten gestützt. Anwendung des Inhibitors -Diethylaminoethyl-Diphenyl-Propylacetat (SKF 525-A) zeigte in vitro eine ausgeprägtere Inhibition der Mikrosomen von mit phenobarbital behandelten Ratten als der Mikrosomen von unbehandelten oder TCDD-behandelten Ratten. Nachweis und Bestimmung von Pentachlorphenol und seinen Metaboliten wurden gaschromatographisch-massenspektrometrisch durchgeführt.

     

Prediction of survival and recurrence in bladder carcinoma

Summary We have followed a large population of patients receiving radiation treatment for bladder carcinoma with respect to survival and recurrence-free survival. Bivariate and multivariate life table analyses have been performed using a set of independent variables. The most important were T class, grade (G), urinary carcinoembryonic antigen (U-CEA) taken before treatment and cytological analysis 4 months after treatment. We compared the usual way of classifying a patient (T+G) with the combination of U-CEA and cytology since the latter two variables seemed to have great prognostic importance. The analyses show that T+G gives the best significance for survival (P=0.0003) while U-CEA and cytology is better for recurrence-free survival (=0.0002). 0.0002).     

Action of the competitive angiotensin II antagonist saralasin during the initial phase of glycerol-induced acute renal failure of the rat

Summary The effects of the competitive angiotensin II antagonist saralasin (1-sarcosine-8-alanine-5-isoleucine-angiotensin II) on renal function in healthy rats and in rats with myohemoglobinuric acute renal failure were studied. Acute renal failure was induced by an intramuscular injection of 50% glycerol (10 ml ·kg^–1). Functional impairment of the glycerol treated animals consisted in a decrease of renal blood flow (electromagnetic flowmeter) and GFR and in an increase of urine volume and arterial blood pressure.In healthy rats saralasin (6 g·kg^–1·min^–1 i.v.) had no renal effects by itself but antagonized the angiotensin II (200 ng·kg^–1·min i.v.) induced fall of renal blood flow and GFR and the increase of arterial blood pressure. Given to glycerol treated animals saralasin did not induce any change of arterial blood pressure, renal blood flow, GFR or the urinary excretion of fluid and sodium.Supported by Deutsche Forschungsgemeinschaft     

Pharmacokinetics of spironolactone in man

Summary Five healthy male volunteers received 500 mg Aldactone^® orally together with 100 Ci ³H-20-21-spironolactone; one elderly patient received 1 mCi ³H-spironolactone without additional cold drug. For 6 days the disposition kinetics of the drug were studied in plasma, urine and feces. The tritium concentrations in plasma reached a peak between 25–40 min after administration amounting to 2–3% of the dose/1. Up to the 12th h, they fell rapidly and showed a monoexponential decline (t _1/2 : 2.57±0.27 days) between the 36th and 96th h. Later, a striking increase in the speed of elimination of radioactivity from plasma (t _1/2 : 1.66±0.21 days) was observed. The biological half-life of labeled material in plasma was longer than that of fluorigenic compounds. 47–57% of the dose were excreted in urine and the remaining amount culd be detected in feces (total recovery 90%). The half-life of the urinary excretion rate was distinctly shorter (t _1/2 : 0.9±0.11 days) than that of total radioactivity in plasma. This, together with an observed increase of the polar fraction in urine from 35 up to 85%, which was accompanied by a decrease in plasma from 55 to 35%, suggests either tubular reabsorption or enterohepatic recirculation of lipophilic compounds. TLC-separation of the lipophilic fraction in urine revealed two previously unknown compounds of which the main congener was identified as 3-(3-oxo-7-methylsulfonyl-6, 17-dihydroxy-4-androsten-17-yl) propionic acid -lactone, as well as canrenone and the metabolites which have already been described (Karim and Brown, 1972; Karim et al., 1975). This metabolite represents the main lipophilic degradation product in urine within the first hours, whereas the 6-OH-7-methylsulfinylspirolactone leveled off and seemed to be an endexcretion product. For further characterisation, the polar fraction was subjected to acidic hydrolysis. The known metabolic pathways of spironolactone degradation are discussed.The paper includes parts of the thesis of G. Luszpinski