Bengt Knave

Occupational exposure to electromagnetic fields in relation to leukemia and brain tumors: a case-control study in Sweden

Occupational exposure to low-frequency electromagnetic fields (EMF) was studied in 250 leukemia patients and 261 brain-tumor cases, diagnosed in 1983–87 and compared with a control group of 1,121 randomly selected men, from the mid-region of Sweden, 1983–87. We based the exposure assessment on measurements from 1,015 different workplaces. On the basis of the job held longest during the 10-year period before diagnosis, we found an association between the average, daily, mean level of EMF and chronic lymphocytic leukemia (CLL). The risk increased with increasing level of exposure. The odds ratios (OR) and the 95 percent confidence interval (CI) for three consecutive levels of exposure were: 1.1 (CI=0.5–2.3); 2.2 (CI=1.1–4.3); 3.0 (CI=1.6–5.8), respectively. No association was observed for acute myeloid leukemia (OR=1.0, CI=0.5–1.8; OR=0.8, CI=0.4–1.6; OR=1.0, CI=0.6–1.9). For brain tumors, the corresponding risk estimates were 1.0 (CI=0.7–1.6); 1.5 (CI=1.0–2.2); 1.4 (CI=0.9–2.1). Different EMF indices were tested. Tasks with frequent or large variations between high and low field-densities (high standard deviation) were more common among CLL subjects. For brain tumors, a prolonged high level (high median values) showed the strongest association. Confounding by place of residence, smoking, benzene, ionizing radiation, pesticides, and solvents was evaluated, and these factors did not seem to have a decisive influence on the associations. We also analyzed other potential sources of bias. For CLL, there were indications of an excess number of low-exposure subjects among non-responders, which, to some extent, may have enhanced but not caused the risk estimates obtained. Our conclusion is that the study supports the hypothesis that occupational EMF exposure is a hazard in the development of certain cancers.

CHANGES IN ULTRASTRUCTURE AND FUNCTION OF THE SHEEP PIGMENT EPITHELIUM AND RETINA INDUCED BY SODIUM IODATE1

The present investigation shows that the membrane properties of the sheep pigment epithelial cells were very rapidly and severely affected by sodium iodate, whereas the effects concerning the neuroretina were delayed. The c‐wave of the ERG was immediately abolished and replaced by a cornea‐negative potential, but the a‐ and b‐waves were preserved for about 80–100 min. Ultrastructurally the plasma membranes (particularly the basal plasma membrane) of the pigment epithelial cells were destroyed or less distinct than normally. The cell organelles were swollen and ruptured. There were indications that the pigment epithelium could no longer participate in the receptor outer segment turnover. The photoreceptor cells were morphologically undamaged, and few or no signs of injury were observed in the inner layers of the retina. The effects upon the neuroretinal functions seen after 80–100 min, consisting of a reduction of a‐ and b‐wave amplitudes, were most likely caused by an inability of the pigment epithelium to maintain in the long run its metabolic and barrier properties. It appears that at an early stage after sodium iodate injection, the present preparation may be useful for the study of the effects on the neuro‐retina proper of drugs and other agents.

A comparative study on the effects of barbiturate and ethyl alcohol on retinal functions with special reference to the C-wave of the electroretinogram and the standing potential of the sheep eye.

The effects of barbiturate (thiopental) and ethyl alcohol on the a‐, b‐ and c‐waves of the conventional electroretinogram (ERG) and the standing potential (SP) of the intact sheep eye were studied and compared. I.v. administration of ethyl alcohol resulted, after some minutes latency, in a large increase of the c‐wave amplitude. A marked positive d.c. shift of long duration and with similar time course to that of the c‐wave increase was observed in the SP after a small negative change. Barbiturate induced slow long‐lasting shifts of the SP with an initial negative and a subsequent positive polarity. Large doses were shown to result in negative‐positive cyclic variations of the c‐wave. For ethyl alcohol, as has been shown for barbiturate, the effect on the c‐wave, thus appears to be linked in time to the effect on the SP. No similarities whatsoever could be demonstrated between the changes of the SP and those of the a‐ and b‐waves. These results lend support to the notion that ethyl alcohol, in addition to its neuropharmacological effects on the neuroretina, may also influence the functions of the pigment epithelial cells in a way similar to barbiturates.

THE ERG AND OPHTHALMOLOGICAL CHANGES IN EXPERIMENTAL METALLOSIS IN THE RABBIT

Retained intraocular iron particles can give rise to changes in the different tissues of the eye, called siderosis bulbi. Retinal damage often occurs at an early stage and is the most detrimental result of siderosis. After introducing electroretinography (ERG) for clinical purposes, Karpe (1948, 1957) showed that pathological changes in the ERG could be correlated to retinal siderosis, which finding has been confirmed in other clinical investigations (Schmiiger 1956; Straub 1961 ; Kozousek 1965; Knave 1969a). In the last-mentioned of these investigations the most case material was presented; 68 cases were selected for analysis, 42 of which with an intraocular iron particle. Localization, duration and degree of encapsulation of the intraocular particles did not explain the differences in the development of siderosis from case to case. The results indicated that minor differences in alloy content might play a role. The clinical results thus pointed to the necessity of an experimental approcli in animals. It should be mentioned that the ERG following intraocular im-

Cyclic variations in the c-wave amplitude of the sheep ERG☆

Abstract The c -wave of the sheep electroretinogram was studied in long-term experiments. It was found that the c -wave amplitude changed as a function of time and these alterations were dependent on frequency of the stimulus flash used. A slow oscillation (frequency about 0.3–0.5 per hr) of the c -wave amplitude was observed, using 1 sec light stimuli and long flash intervals (2 min). Shorter flash intervals gave rise to oscillations with a frequency of about 2 per hour. These fast oscillations initially were of relatively large amplitudes but decreased with time and reached a constant level after about 100 min. Shortening of stimulus duration (0.1 sec) resulted in c -waves of less amplitudes, but the cyclic variation pattern described above did not change.

SELECTIVE EFFECT OF A NEW ANTITUBERCULOUS DRUG, RIFAMPICIN, ON THE c-WAVE OF THE SHEEP ELECTRORETINOGRAM

Quite recently it was found that i.v. injections of 14C-labelled rifampicin gave rise to marked radioactivity in the w e a l tract (and presumably in the pigment epithelium) of the pigmented mouse (Boman 1973). This finding contrasted to the faint radioactivity obtained in the albino mouse. The difference in distribution pattern of 14C-labelled rifampicin between pigmented and albino mice was interpreted as being due to an affinity to melanin in the uvea and the pigment epithelial cells of the pigmented mouse retina. Recently an ERG method was developed which allowed studies of the slow components of the sheep ERG (Knave, M ~ l l e r & Persson 1972). One of these slow components in the c-wave, which is known to reflect the activity of the pigment epithelial cells in vertebrate retinas (Noel1 1953, Brown & Wiesel

The morphology of the sheep retina. I. The receptor cells and the pigment epithelium.

The present investigation was undertaken in order to provide a necessary ultrastructural basis for the complete interpretation of recent findings on the electrophysiology of the sheep retina and on the influence on retinal function of certain drugs and toxic substances. The sheep retina was shown to be a mixed retina with a rather large number of cones. The receptor cells were conventional in shape. Typical differences in light and electron optical density between rod and cone ellipsoids could be explained as differences in stainability of the mitochondrial content. Specific connections between the outer segment disks and the plasma membrane as well as the occurrence of phagosomes in the pigment epithelial cells are discussed in relation to the development and the renewal of the receptor outer segment. No melanin granules were seen in the pigment epithelium of the investigated specimens, which were all taken from the tapetal area of the fundus. The possible relation between lipid‐like bodies in the pigment epithelium and vitamin A metabolism is discussed.

Changes in ultrastructure and function of the sheep pigment epithelium and retina induced by sodium iodate. I. The ultrastructure of the normal pigment epithelium of the sheep.

The normal ultrastructure of the sheep pigment epithelial cells is described as a basis for the interpretation of toxic (sodium iodate) effects on these cells dealt with in two following papers. The morphological features of the different cell membranes and cell organelles, particularly the phagosomes and the lipid droplets, are discussed in relation to renewal of the photoreceptor outer segment, pigment epithelial and retinal metabolism, barrier mechanisms and electrical properties.

THE ERG AND OPHTHALMOLOGICAL CHANGES IN EXPERIMENTAL METALLOSIS IN THE RABBIT: II. Effects of steel, copper and aluminium particles

Retained intraocular metal particles can give rise to tissue damage in the different parts of the eye, called metallosis bu2bi. Retinal damage occurs at an early stage and is the most detrimental results of metallosis. This damage has been studied by means of ERG in clinical works (Karpe 1948, 1957; Schmoger 1956; Straub 1961; Kozozisek 1965; Knave 1969a). In the clinical investigation by Knave (1969a) the results indicated that ininor differences in the alloy content of steel particles might be important for the occurrence of siderosis bulbi. This has been studied more closely in the rabbit in the present work, which also can be regarded as a complement to a recent investigation on the long-term effects following the implantation of pure iron particles into the rabbit vitreous (Knave 1969b). Moreover, the ERG following the intravitreal implantation of copper and aluminium particles has also been studied in the present work, since this has not been done before and since particles of copper and aluminium, next to those of iron and steel, are the most commonly occurring intraocular metal foreign bodies in the human eye.

A New Method for D.C. Registration of the Human ERG at Low and Conventional Stimulus Intensities

A new method developed for d.c. registration of the human ERG made it possible to study retinal functions that have not previously been studied clinically, e.g. the retinal responses below the b-wave threshold and the c-wave. It is hoped that this new method may make it possible to diagnose earlier certain pigment epithelial and retinal disorders induced by drugs or caused by other factors.