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Chronic Effects of Mercury on Organisms:

The micromercurialism phenomenon in mercury handlers



NOTE: These are notes are incomplete.
Please refer to the original for scientific research.


THE MICROMERCURIALISM PHENOMENON IN MERCURY HANDLERS

The phenomenon and clinical aspects of common mercurialism are well known; the symptomatics of micromercurialism, caused by small mercury concentrations (hundredths of a mg/m3) are insufficiently defined. Further study, toxicological experimentation and clinical observations are needed.

Analysis of symptomatic complexes characterizing relative toxic affects deepen not only our understanding of the phenomenon and its pathology but permits more successful early diagnosis. In occupational pathology the early diagnosis problem is distinct from its general, clinical prophylactic significance. One must agree with N. A. vigdorchik (1940) who said that the early diagnosis of an occupational pathology "is a timely danger signal, and a timely signal is the basis of effective prophylaxis."

A. Stock (1926) first described micromercurialism and noted especially changes in psychic function. He characterized micromercurialism symptoms in three groups according to degree of intensity of the phenomenon.

According to A. Stock, first degree micromercurialism results in lowered working capacity, increased fatigue, light nervous excitability. Often in the second degree there is swelling of the nasal membranes, progressive weakening of memory, feelings of fear and loss and self-confidence, irritability, headaches. Simultaneously there may be catarrhal symptoms and upper respiratory discomfort, changes in the mucous membranes of the mouth, bleeding gums. Sometimes there are feelings of coronary insufficiency, shivering, quickening pulse, and a tendency toward diarrhea. Third degree micromercurialism is characterized by symptoms approaching those of regular mercurialism, but to a lesser degree. The basic symptoms of this stage are: headaches, general weakness, sleeplessness, decline in intellectual capacity, depression. Among other signs are tears, diarrhea, frequent urination, a feeling of pressure in the cardiac region, and shivering.

The diagnosis of micromercurialism in some cases is quite difficult.

M. P. Minker (1927) at the XV Scientific Conference of the Leningrad Institute for the Study of Occupational Diseases said that most cases of micromercurialism appear as an ailment of the respiratory or nervous system, depending on what predominates in the clinical picture.

A. M. Gel'fand (1928) also noted that "sometimes mercury poisoning in patients is mistaken for other diseases."

A. N. L'vov (1939) cited cases of micromercurialism misdiagnosed as neurasthenia, hysteria, etc. He notes that among mercury industry workers in three years there were only a few cases of chronic industry poisoning reported, while qualified pathologists frequently reported the phenomenon of micromercurialism among workers.

A most interesting study by this institute involved workers having continuous exposure to small concentrations of mercury vapor.

This chronic poisoning by small mercury concentrations is reflected in the total functional-neurotic condition, CNS effects and in cardiovascular-activity. Ya. Z. Matusevich and L. M. Frumina (1934), investigated worker neuroses acquired after the prolonged action of small mercury concentrations which caused functional disturbances in the vegetative nervous system.

In surveying the symptoms of chronic mercury poisoning, we note its primary destructive effect on the subsortical ganglia. Much evidence of higher nervous and functional disturbances are in the works of M. M. Gimadeyev, 1958; E. A. Drogichina, L. G. Akhnyanskaya, D. A. Ginzberg, et. al., 1954; V. N. Kurnosov, 1962; M. N. Sadchikova, 1954.

Functional changes in the internal organs, especially the heart, in micromercurialism have been described by A. A. Orlova, 1954; liver and kidney disturbances, Kh. Z. Lyubetskiy, 1953; effects on endocrine organs, especially the thyroid gland, R. N. Vol'fovskaya, 1928; M. A. Kazakevich, 1933; A. M. Manayenkova, 1957.

Differentiation studies, permit an explanation of micromercurialism not only among persons occupationally exposed to mercury, but among those subjected to secondary exposure through occupation of previously contaminated sites.

Most of the subjects were apparently healthy, although many of them presented a series of complaints. Most of these were subjective symptoms reflecting feelings of weakness. To a greater or lesser extent there were complaints of mercury impairment, insomnia and emotional disturbance. Also included were apathy, crying, daytime sleepiness with nightly insomnia and often a progressive decline in work capacity. These complaints were repeated from year to year in many of the subjects, however non-specific complaints predominated. These were separated by symptomless periods - the first feature of the initial appearance of micromercurialism.

This feature establishes the "mercury" etiology and serves to differentiate the above complaints from analogous symptoms appearing as a consequence of general somatic diseases.

The second feature - the presence of complaints during the entire period of mercury contact. We tried to determine the exposure time required to produce the first subjective signs of a mercury effect and how the first symptoms later develop into micromercurialism. This includes waiting for the first complaints, recording symptoms of developing neurasthenia. Of 144 persons in this group who displayed asthenovegetative symptoms, the indicated signs appeared most often in the first six months of contact with merry, and especially in the first year - in six persons, in the fifth - in 15, in the sixth - in 18, in succeeding years - in the rest (45 persons.) Ninety-two of 137 persons had symptoms during the first - sixth years of working with mercury. In seven cases, micromercurialism symptoms were detected after ten years of work with mercury. In order to establish the presence or absence of phenomena of specific etiology, special attention was paid to data on anamnesis and also to a series of special observations (olfactometry, Teleky's symptom, uptake of radioactive iodine by the thyroid gland, etc.).

The data shows that asthenia appearing as a consequence of general somatic illness is very like that of "mercury" etiology, but differ in analogous subjective symptoms. In the first instance complaints of emotional malaise are usually absent; in the second, they dominate over the rest and, as a rule, are characterized by an increase in general irritability and sensitivity, annoyance, rapid mood changes, apathy, tendency towards crying.

Naturally, we qualify this syndrome as having a mercury etiology not only because of such complaints but as a result of detecting such objective signs as tremors, enlargement of the thyroid gland and its increased uptake of radioactive iodine, stable and increasing (under the influence of unithiol) excretion of mercury in the urine, etc. An important aid in establishing the occupational etiology are hematological shifts, comparison of their dynamics and the development time from onset of other (subjective and objective) symptoms of mercury effects.

At first glance it appears that the asthenic-vegatative syndrome occurs more often in women. However, statistical treatment of the obtained data indicate that it occurs equally frequently among men and women to mercury intoxication, although this is the conclusion of O. A. Gridgorova, Ya. Z. Matusevich and L. M. Frumina (1934.)

Analysis of the frequency of the asthenic-vegatative syndrome as related to age showed that, in both groups, it occurred more often in persons over forty.

The absence of a true relationship between the frequency of this syndrome on the one hand, and the age composition of the workers on the other, confirms earlier data on amnesia studies about the first signs of micromercurialism even in the first years of mercury exposure.

Our data analysis indicates that the effect of low mercury concentrations on workers' systems seems to invalidate concepts of age and work experience as factors. This does not mean that these factors cannot, in some cases, increase the intensity of the toxic effect and be a determining factor in the frequency and development of the micromercurialism phenomenon.

The asthenic-vegatative syndrome of "mercury etiology differs from the analogous symptomatic complex of somatic illness in its manifestation of emotional sensitivity which takes on the relatively stable character of micromercurialism.

Among these first, of all, are neurological symptoms, usually digital tremors of the extended hand. These tremors are usually intermittent in nature, appearing, as a rule only during agitation.

Among the neurological phenomena neuralgia and radiculitis, neuritis connected with the appearance of asthenia appears three times as often in "mercury" groups as in groups where this complex is absent. Neurological symptoms seldom occur up to age 39 and more often among older people. Note that a group of neurological symptoms not included are a series of vegetative shifts, such as tendency to tachycardia, pulse lability, cardiovascular fluctuations, etc.

There are also such symptoms as red dermographism, increased tendency towards perspiration, etc. These shifts correspond to changes in certain endocrine functions, especially of the thyroid gland. An enlarged thyroid was noted in the first group in 55, and in the second in 18 persons. Thyroid dysfunction occurred in both groups up to age 29. A significant number occurred in those who had not been employed very long (from 1 - 4 years.)

Analysis of the data make it impossible to ignore the high percentage of cases of functional disorders of the cardiovascular system, liver, digestive tract, and changes in the mucosa of the mouth. There are complaints of chest pains or "colic," heart palpitations and a "sinking" heart in both groups, 29% in the first ad 36% in the second. In an objective study of cardiovascular lability, vascular dystonia occurred in 34 and 39% of cases respectively. Especially interesting is data on cases of hypotonia (33% of persons in the first group and 31% in the second.) Simultaneously, an increased arterial pressure (7 and 12% of cases) was noted. The majority of the subjects who had cardiovascular problems were over forty, but there was a large number of such cases among the 20 - 29 year-old group. Generally this symptom was directly related to length of contact with mercury.

Next in specific importance are functional shifts in the liver (first group 16%, second group 27% of cases.) Note the number of persons 30 - 49 years in the first group and above fifty years in the second. Stomach and intestinal disturbances generally were accompanied by substernal pains, lowered appetite, a feeling of pressure under the sternum, nausea and vomiting in 11 and 25% of cases respectively. This symptomatic complex is like the picture of secretory neurosis of the stomach.

Some persons in contact with small amounts of mercury have many complaints about the mouth and lining, (a metallic taste in the mouth, bleeding gums, increased detachment of the lining.) Some cases involve hyperemia of the mucosa and others mercury in the edges.

Mouth changes, shown to be of occupational etiology make up 10.3 and 21% of cases respectively. indicatively, of 77 persons having these shifts, 69 also had an asthenic-neurotic syndrome of etiology.

In the third group (the smallest - 68 persons) more than half were 40 - 50 years and older. The length of employment of over half of these persons in mercury contaminated places was five to ten years and more. A feature of this contingent was, first, an absence of direct (caused by specific occupation) contact with mercury, second, predominance of older people. Thirty-five persons had subjective neurological symptoms, in 22 objective nervous system changes, particularly vegetative. almost half (32 persons) manifested an asthenic-neurotic syndrome, which in 27, was of mercury etiology. Indicatively, functional disturbance of the cardiovascular system which appeared in 19 persons, liver changes in 14, stomatitis in 11, were observed in persons with an asthenic-neurotic syndrome of mercury etiology. An enlarged thyroid appeared in three persons, decreased arterial pressure in fifteen, increased pressure in six.

A comparison of this data with that of other authors (Ya. Z. Matusevich, I. L. Frumina, 1954) shows that in modern mercury use, where at the respiratory zone, the concentration is at or near the permissible limit (0.01 mg/m3) or at even lower levels, the effect is of a more latent or minimally symptomatic character than described earlier. the frequency of subjective and objective symptoms in persons contacting low mercury levels has decreased under modern conditions. However, this decrease is far from that deemed desirable for significant contingents in contact with mercury.

The data suggests a high number of "specific" functional shifts and disturbances and a general "nonspecific" syndrome of the initial and later phenomenon of micromercurialism. Our studies of workers in Kiev establishments have universal application. We will speak of workers in a Moscow enterprise, a shop of which, over a twelve year period had a mercury level from 0.006 - 0.04 mg/m3. This enterprise of the electrovacuum industry, possessed not only possibilities of direct mercury contact, but of mercury effects arising from technical processes involving low mercury concentrations and high surrounding air temperatures. This feature of the industry was described by us with I. V. Savitskiy and R. Ya. Shterngarts (1965) in which they stressed the absence, in earlier published works, of the treatment of the problems of micromercurialism, of such surveys of a contingent of persons subjected to the effect of small mercury concentrations on a background of high air temperature. As we have already stressed, such a combination prevails not only in the electrovacuum industry, but in metallurgical, electronic and chemical plants, etc.

In the study previously discussed, the first group worked under industrial conditions where the aerial mercury concentration was 0.01 - 0.05 mg/m3, the winter temperature, 16 -24°C, and the summer temperature 26 -31°C. In the second group were persons having contact with 0.001 - 0.01 mg/m3 at temperatures of 28 - 38°C in the winter and 40 - 42°C in the summer. The control group was one having no contact with mercury but working at high temperatures (38 - 42°C.)

Observational analysis of these groups indicates that the symptoms complex is of occupational origin.

Comparative symptomatic frequencies between the two groups showed more complaints in the first group, while there were more objective symptoms (tremors, enlarged thyroid, etc.) in the second group. The differences can be attributed to the effects of high temperatures on the workers.

Thus the materials presented above signify micromercurialism in the subjects as a consequence of prolonged exposure to mercury in concentrations close to 0.01 mg/m3.

It is instructive to compare these results with those from observations of control group persons. The number and frequency of complaints and of objective deteriorations was 2.5 - 3 times rarer than in the basic group. Only 13.4% of the controls complained of insomnia, sweating and emotional sensitivity at the same time this incidence in the first and second group was 28.0 - 50.0% respectively. Tremors of the hands and eyelids and thyroid enlargement occurred in 8 - 12% of controls, and in the basic groups 28 and 37%.

The above materials on medical surveillance of persons in "mercury" occupations for the last seven years at the Moscow Electric Lamp Factory are even more argumentative from the point of view of conclusions generated and linked with clinical and statistical materials on worker studies at the same site worked out by E. I. Gol'man (1964). All data embraces the twelve-year period of the subjects and is quite conclusive.

Data obtained during this period on the time required for the first symptoms of mercury effect to appear conforms to other data above; 120 of 140 persons studied experienced different asthenic-vegatative complaints and symptoms determined to be initial signs of mercury effect. These symptoms appeared during the first five years of employment. In particular in the first year, it occurred in 77 persons, in the second, in 30, in the third, in 13 and in the fourth and fifth, in 4. Increased appearance of a mercury effect is observed in the third year after beginning work with mercury. According to E. I. Gol'dman, 36.3% of his subjects displayed early symptoms of micromercurialism after one year's employment, 77% after two years, and 15% after three years. Thus the tell-tale signs have usually appeared by the second year of exposure to mercury. Although most persons have displayed symptoms by the sixth year of mercury contact, in some cases ten or more years were required.

We investigated the distribution frequency of vascular hypotonia among persons in contact with low mercury concentrations. We found that, among the first group, the incidence was 33%, and in the second group 31%, which conforms to the data of E. I. Gol'dman (1964). We encountered increased arterial pressure more often than E. I. Gol'dman did. We did not notice such a difference in frequency of the latter in persons with the asthenic-vegatative syndrome in comparison with the rest of the subjects. We found vascular hypertonia to be absent among luminescent lamp workers having the most contact with metallic mercury, although 15% of this group were over 40.

Among these persons a significant percentage were exposed to both mercury vapor and high air temperatures. This group consisted of 122 persons: 69 men and 53 women. The majority were between 30 - 39 years (81 persons.) Most had been working with mercury for 5 -10 years (92 persons.)

Sixty-three persons (56.2% of the group) were diagnosed as having an asthenic-vegatative syndrome of mercury etiology and forty persons (35.6% of cases) had low blood pressure. Six persons (5.3%) had increased arterial pressure. In recent years there has been a decrease in the number of persons with arterial hypertension. S. D. Reyzel'man found lowered blood pressure in a group of mercury workers in 50% of the men and 68% of the women. R. N. Vol'fovskaya found hypertension among 42% of surveyed persons in "mercury" occupations. According to other data the total number of cases was 60% of all subjects studied, or 44.4% (I. M. Livshits.) Ya. Z. Matusevich and L. M. Frumina found hypertension in 50% of the men and 68% of the women.

In looking at results of hematological studies we note that the number of subjects with less than 70% hemoglobin increases with length of work with mercury. Thus, after one year of employment, decreased hemoglobin occurred in 29.8% of cases and among persons employed ten years or more, it occurred in 40.59%.

Analysis of erythrocyte counts showed that, with increasing length of employment (one to ten years,) the number of persons with less than 3,500,000/mm3 increased almost two-fold (from 14.49 - 26.73%.) At the same time there was a five-fold decrease in the number of patients with counts of over 4,500,000 (from 36.17 -7.92%.)

Among persons with the astheno-neurotic syndrome, showing signs of a "mercury" etiology, the number of subjects in whom hemoglobin was less than 70% was 40.14%, and the number who had less than 5,000,000 erythrocytes was 27.73% of the total.

Along with the hemoglobin studies we determined the bilirubin content of the blood and found it above "normal" (0.06 -1.2 mg%) in a significant number of cases (48.9%) of persons having contact with mercury. A higher percent (57.59%) was found in the group having an astheno-neurotic syndrome of occupational (mercury) etiology.

There was an increased reticulocyte level in the blood of persons with asthenic-vegatative syndromes (10.28%) Interestingly, this percentage decreases with length of employment. Thus, among persons with four years of less experience, the reticulocyte level was up in 31.02%, and in persons with ten or more years experience, in 8.14%.

The white cell count in these subjects was below 6,000. With increasing length of experience, there was an increase in the number of persons with a decreased leucocyte count (from 15.53 to 55.44%,) and the number of persons with a count higher than 8,000 fell three-fold (from 46.8 to 14.85%) Lymphocytosis occurred in 19.89% of cases. Eosinophilia (over 5% eosinophib) occurred in 12.5% of cases, and eosiniphilopenia -- in 14.6%. Eosinophilopenia decreases from 27.6% to 0.

There is a slow development over the years of hypo-chromic anemia with the presence of hemolysis leading to increased bilirubin in the blood (indirect reaction.) Granularity of erythrocytes increased in 29% of cases and corresponds with increased regenerative activity of the bone marrow. On the other hand, the decrease in the number of persons with increased reticulocyte contents, the increase in leukopenia, the growth of eosinophilopenia and the absence of nuclear shifts in leucocytes increases with length of employment, and the prolonged effect of low concentrations with length of employment, and the prolonged effect of low concentrations is a gradual inhibition of the hematopoetic function of the bone marrow.

Materials characterizing the urinary mercury content were analyzed. In our laboratory 637 analyses for mercury associated with low external concentrations were done in five years, using a method worked out by S. L. Ginzburg (1948.) In time, certain parts of the method were improved significantly and a standard solution was used (iodine and potassium iodide containing 0.001 mg Hg/ml.)

The majority of urinary mercury levels is independent of length of subject contact with mercury. In some cases no urinary mercury was detected. The unithiol uptake was followed (0.5 gm twice a day.) There was later increased urinary mercury content only in cases where mercury had previously been found in the urine and is connected with increased release of mercury from the depot under the influence of unithiol. Other studies confirmed the release of mercury under the influence of unithiol administered prophylactically or diagnostically (S. I. Ashbel' and V. A. Tret'yakova, 1958; A. A. Model', 1959; G. A. Belonozhko, 1959, et al.) It must be stressed that when unithiol (in some persons) suddenly increased the urinary mercury output, there was a short term decline in general well being. As a rule patients complained of powerful headaches, appearance of a metallic taste in the mouth, progressive decline in working ability and increase in general weakness. S. I. Ashbel' and V. A. Tret'yakova observed this decline from the depots" as we observed it in patients with the asthenic=neurotic syndrome in the absence of visible toxic damage. In all subjects mercury was not excreted regularly; sharp increases were followed by drops to the levels of healthy persons who had no contact with mercury.

Persons having contact with low mercury concentrations excrete mercury in quantities on the order of thousandths, hundredths or tenths of mg/1. Therefore there is no correlation between the amount excreted in the urine and the presence of subjective or objective symptoms. This data does not justify a correlation between the urinary mercury content and length of contact with mercury.

Our data suggests that mercury is taken into the body, circulates in it for a long time, and is only slowly excreted.

The elimination of mercury often increases under harmful stress such as lowering of the general reactivity of the body, when there is a release of mercury from the depot and its circulation in the blood. For example, during an influenza outbreak in 1959 mercury was detected in the urine of workers in the transformer station. Most of these persons suffered from influenza and their urinary mercury output rose sharply.

Our data also shows that there is increased urinary mercury output under the influence of unithiol. This is usually detected in cases where the micromercurialism is of a latent character and the analysis of the asthenic-vegatative syndrome is not "specific" for a mercury etiology.

Studies of olfactory sensitivity have been known by A. Z. Dubrovskiy (1954), in which olfactometers measured odor intensity during the investigation. His olfactometer made it possible to study the degree of olfactory and trigeminal sensitivity of smell in response of the release of peppermint oil droplets of 30% acetic acid solutions.

The determinations of olfactory sensitivity used a 170 person control group taken from the experimental group made up of employees of the KIP, 67 persons, departmental personnel of polytechnic institutes and the institute of Hydrology and Hydrotechnology AN UkrSSR, and also 92 persons who had spent a long time in places contaminated by earlier mercury use.

The results showed that olfactory sensitivities in both groups corresponded. Sensitivity shifts depended on how long a subject had been accustomed to the industrial premises. Threshold sensitivity was highest in persons who had been exposed to mercury contaminated sites for a long time (40 -45* units of tonometric pressure. *The first number refers to olfactory stimulation; the second to trigeminal.)

Besides threshold sensitivity he studied adaptation to odor at threshold concentration and the recovery time after olfactory loading by vapor of a volatile substance. Negative responses were taken every five seconds and the number of negatives studied at 60 - 120 seconds. The adaptation time to peppermint oil was low. After ten seconds 54 persons had adapted to this odor at the same time that 36 persons in the control group required 30 seconds. In two minutes 83 persons in the experimental group had adapted while only 68 of the control group had done so. Analogous results were obtained with acetic acid.

A third indicator, characterizing the recovery of olfactory sensation at the threshold quantity, was noted in 37 cases of the experimental group within 30 seconds and within two minutes in 69; while in the control group the time corresponded in 72 and 92 cases. There was hyperosmia in 12 persons (221%).

With adaptation time shortened, less time was required for responses. In the healthy group, the time varied within wide limits - 30 to 45 seconds -- 30 minutes (average for peppermint 1.5 - 2.4 minutes and for acetic acid 1.1 - 2.0 minutes). In the mercury group adaptation time was much shorter (8 to 10 seconds - 2 minutes). Recovery of olfactory sensitivity under load required 30 - 100 seconds for the control group and 45 - 146 seconds for the mercury group. In the other cases threshold sensitivity was 60 - 80 units and the recovery time 7 - 10 minutes and longer. This occurred in cases of recorded micromercurialism. However, some cases (17%) with high olfactory sensitivity showed a tendency toward increased adaptation time and shortened recovery time (of threshold sensitivity) after olfactory load. Generally in these persons mercury effects were absent.

Analogous data was obtained for the KIP plant, and academic and industrial laboratories.

Thus, analysis of olfactometric indicators in subjects correspond to a biphasic mercury effect on the olfactory analyzer. The first phase is the decrease in threshold sensitivity, and speeding up on the recovery period after load. The second phase is increased threshold sensitivity and a prolonged recovery time. In the first phase, in cases where other functional shifts have been recorded frequently in the thyroid gland, a series of vegetative indicators, especially in liver function, a depression in threshold sensitivity under repeated stress is noted.

In persons having contact with low mercury concentrations (primarily with the appearance of the asthenovegetative syndrome) we studied the functional state of the thyroid gland. Some of these people worked at the KIP plant. Among them were 36 men and 31 women. Their ages, between 30 - 45 years (43 persons), over 45 (24 persons). They had worked with mercury for 5 - 10 years.

Results are shown in Table 20, differentiated on the basis of radioactive iodine uptake by the thyroid. The characterizations were as follows: less than 10% uptake, below normal; 10.1 - 15%, low borderline normal; 15.1 - 25%, average; 25.1 - 30% high borderline normal; above 30%, increased functional activity.

As is evident from the table there are definite variations in the determined quantities among the subjects. Thus, in the control group as among the men and women there were persons in whom (24 of 45) the uptake of radioactive iodine was normal. Some subjects studied were generally above normal but there were five persons whose thyroids took up more than 30% of the radioactive iodine. A different character is seen in the profile of persons having contact with mercury. Among these there is a definite tendency toward increased thyroid activity at the high normal borderline. Indicatively, persons with low and average uptake made up 33% of the group (23 of 67 persons). Not only after 24 hours from the moment the isotope was administered, but also during the 2 hour investigation, the percent uptake of radioactive iodine by the thyroid gland in this group exceeded the norm in many cases (in conformity with the literature data, the normal thyroid uptake after 2 hours is 5 - 9%). There is a tendency toward an increase in this with an increase in exposure: to 6 - 8 hours. In almost all cases (61 of 67), the maximum uptake is noted within 24 hours from the administration of the isotope. Note that in this period 5 of the persons had an uptake rate below 10%.

Statistical treatment of this data indicates the reliability of the quantities. Thus, in comparing results taken twenty-four hours after administration of the isotope, in a group of men with more than eight years experience (ages from 30 - 45) the average uptake and margin of error was 32.17 + 2.24, at the time that of an analogous group was 20.8 + 2.6.

In cases where the asthenic-vegatative syndrome is present, thyroid activity is increased, the objective signs include red dermographism, finger tremors in the extended hand, sweating and, in a number of persons, enlarged glands.

Radioactive iodine uptake by the thyroid gland under even low quantities of mercury can increase significantly. Persons who show increased uptake of the isotope, as a rule, show symptoms indicating glandular dysfunction; enlargement, finger tremors, emotional sensitivity, etc. This conclusion agrees with the observations of A. M. Monayenkova, M. N. Ryzhkova, and M. I. Smirnova (1959).

Small quantities of mercury effect the so-called Teleky Symptom (B. B. Koyranskiy, 1930; B. B. Koyranskiy and Ye. Ya. Benediktov, 1931) although this is questioned by others (N. A. Vigdorchik, 1927, 1928: I. G. Gel'man, 1935). The reason for this controversy is the difference and insufficiency in the methods used by the authors in determining data.

Therefore we devised a method, differing from previous ones using a special device based on the Kollen dynamometer and designed to test the strength extension.

The device has a scale, indicating in kilograms the strength of a muscle compressing a piston. Thus there is direct registration of results on the scale. The construction of the device permits measurement of the angle of the wrist.

The measurement proceeds as follows: the subject rests his right hand in the special holder running along the location of the forearm and hand. Then the forearm and hand are lightly fixed as shown, the wrist freely makes a right angle.

Fixed thus, the subject slowly extends the wrist flexing the plastic which pulls the piston. An arrow indicates the results on a scale. Then the right hand is freed and the left fastened and the procedure repeated.

In working out the recommended method (and in the construction of the device used in the experiments) we tried to remove insufficiencies found in previous methods. First, muscle power is measured at the maximum drawing out of the piston. Second, our results are not indirect data derived from units of work for "comparison" with unit strengths, but are absolute indicators. Third, the device is constructed so that the transmission of movement is not lost in intermediate movements lowering the accuracy of the results: there is direct transmission of wrist movement to the arrow on the scale. The device is comparatively compact and does not need attachments. It is easily used in mass worker surveys conducted in production conditions.

In the KIP plant, in academic and industrial laboratories, and among medical students we determined the extensor strength in 230 people.

In most persons, both in the experimental and control groups, the strength of the right wrist was stronger than that of the left. In 88 persons (76.5%) the extensors of the right wrist were weaker than those of the left.

These results correspond with those of others, especially B. B. Koyranskiy (1929). The author found a stronger right hand in 60% of workers who had not had contact with toxic substances. In the control group the right hand was stronger in 76.5 percent of cases, in personnel of "mercury professions" in 51% (59 persons). To this group between the left and right wrists (23% as opposed to 17%). However, comparison of the indicated quantities by the standard error method does not confirm this difference. There were more than three times as many persons with weak extension in the experimental group as compared to the control group. In this case the percent of Teleky's symptom was statistically reliable. The data obtained confirms the validity of predicting the possibility of micro mercurialism. The absence of a definite correlation between the frequency of distribution of Teleky's symptom and the appearance of micromercurialism indicates the possibility of its development independent of other symptoms, characteristic of mercury's effect on the organism.

The data of B. B. Koyranskiy shows that the higher the age the fewer the people contacting toxic substances who have weakened right hand extensors. Our studies showed that the 20 - 39 years age group was predominant (77.6%). This is thoroughly reflected in the obtained results.

Below is discussed material from clinical observations (from the data of occupational disease clinics of the Kiev Institute of Industrial Hygiene and Kiev medical Institute).

Data on 136 persons (81 men and 55 women) were studied. The age range were as follows: under thirty, 30 persons; 30 - 39 years, 62 persons; 40 - 50 years, 30 persons; over 50, 14 persons. Their occupational distribution: instrument makers and glass blowers, 30; electricians at transformer stations, 10; other occupations, 10; industrial and academic engineering and technical personnel, 26; medical workers, 8; personnel of scientific-research institutes and graduate school personnel, 34; employees of other enterprises, 6.

Work experience data: 34 persons, up to 4 years; for 68, 5 - 10 years; and in 34, more than 10 years.

These were ambulatory patients who complained of headaches, dizziness and all of the other subjective symptoms earlier described. In some bleeding gums, heart palpitations, impotence, were observed.

Neurological examination revealed a lowering of corneal reflexes, weakened convergence, an increase in tendon, periostal and skin reflexes with a broadening of the reflexogenic zone seldom producing irregular reflexes. changes in the sensitivity sphere is characterized by depression of surface types of sensitivity of the distal sort and muscular tenderness. In almost all cases there were fine tremors of the fingers and eyelids and of the fingers in Romberg's position. Disruption of coordination (finger-nose, etc.) was not observed. In some cases there is horizontal nystagmus or sensitivity of the eyeball.

Neurological symptoms have much the appearance of the asthenovegetative syndrome observed in a series of other effects of an exogenic and endogenic nature. Considering this relationship and the necessity for accurate differentiation of the asthenic-neurotic syndrome of mercury etiology from related "general somatic" disorders, we conducted a series of special investigations which established that: from the standpoint of cortical neurodynamics, changes in the functional state appear most often, as in more rapid nystagmus, under strong stress.

Most of the subjects had changes in the vegetative nervous system: increased sensitivity to temperature changes, especially to cold, periodic hot flashes in the head, neck, chest, hyper-salivation and increased sweating. Some of them had changes in skin color and more or less acrocyanosis, changes in the pilomotor reflex, and erupting red dermographism.

The general background of vegetative-vascular reactions as determined under pharmacological and thermal stress and characterized by insensitivity and variability. High unconditioned pressure reflexes predominated in caffeine and cold stresses according to A. A. Model' (1961) and appears specific for mercury effects.

In characterizing other clinical changes, we agree with A. A. Model' (1961) that "...discovery under hospital conditions of shifts in cortical neurodynamics, a disruption of the functional state of the vestibular analyzer and changes in vegetative-vascular reactions can be regarded as the result of rearrangement of the functional activity of the whole organism with changes in the cortical and subcortical interactions, indicating an incompetence in neuroeflex adaptive mechanisms."

Descriptions of shifts and disruptions of mercury etiology appear as a result of analysis of therapeutic effects observed in the clinic during treatment of patients displaying micromercurialism. This effect, caused by normalization of the given disturbance, appears more quickly and was developed to a greater degree than, when in the complex of therapeutic substances, unithiol is used.

For example; Subject V., age 34, a thermometer-maker with five years' experience where the mercury vapor concentration in the air of the work zone was 0.01 - 0.03 mg/m3. In the course of his occupation he developed systematic muscular traction of the left humerus and wrist when filling capillaries. He felt ill for six months without visible cause and complained of headaches, intensifying toward the end of work or when he was agitated. He felt dizzy and sleepy and out of adjustment. At the same time he felt astringency in the left hand and pain in the right hand.

His pulse was 68/min., blood pressure 120/80 mm, the heart, lungs and internal organs appeared normal.

Neurological changes, including eyelid tremors in Romberg's position and positive Telekey's symptom, indicated mercury effects. His urinary mercury content before unithiol was 0.0187 mg/1 and 0.075 mg/1 afterward. Blood analysis: hemoglobin -78 units (13%), erythrocytes 4,310,000, leukocytes - 4000, oesinophils - 4%, segmented -59%, monocytes - 6%, ESR - 8 mm/hr. X-rays were normal, and the conclusion of the clinic was an asthenic-neurotic syndrome of "mercury" etiology and and occupational neuromyalgia of the right hand.

In this case the indicated nervous system changes appeared after one to two years' exposure of low concentrations of mercury. In the absence of complicating disorders, the increased urinary mercury output after unithiol indicated the "mercury" etiology of the asthenic-neurotic syndrome.

In another case:

Subject K., age 44, was a machinist - assembler of measuring devices, had worked thirty years and had been in contact with mercury for fourteen (hand -filling manometers, thermometers and other devices). The aerial mercury concentration in his work zone was 0.01 - 0.03 mg/m3. He complained of headaches, dizziness, increased irritability, emotional al extremes, insomnia, apathy, trembling of the hands when attempting delicate motions and when under stress. Earlier he had been relaxed and amiable but in the last year, because of hand tremors and a tendency toward tears, strengthened by agitation, left his work. Additionally he complained of weakness, nausea, loss of appetite and frequent liquid stools. He had felt ill about six years. His pulse was 80/min, blood pressure 100/55 mm, heart enlarged toward the left about 1 cm., cardiac rhythm was regular, his lungs appeared normal. he had a sensitive stomach. It was sensitive to palpations on the left side had a spastic colon and his tongue was moist and coated with a white film. He had some horizontal nystagmus, and 48 kg strength in both hands, insufficiency in Romberg's position and fine tremors of the fingers of the extended hand. Teleky's symptom was absent. The urinary mercury level was changed only after injection of unithiol (from traces to 0.047 mg Hg/1). Blood analysis: hemoglobin - 90 units 3%, segmented cells - 61%; lymphocytes - 25%, monocytes - 8%, color indicator, 0.84; ESR - 3 mm/hr. X-rays of the digestive tract showed hyperplastic gastritis. He had spastic colitis localized in the sigmoid region. Conclusion of the clinic: Asthenic-vegetative syndrome of mercury etiology and spastic colitis. In this case a man suffering from chronic illness of the gastrointestinal tract was in contact with mercury. He had the asthenic-vegetative syndrome with neurotic symptoms predominating. The correspondence of this syndrome with the presence i the urine of mercury after injection of unithiol is illustrative to the clinical symptoms of micromercurialism.

Other case histories are quite similar; lighter manifestations coupled with briefer terms of employment indicate initial stages of micromercurialism.

The neurological symptoms in the given cases were characterized by the presence of neurotic and asthenic phenomena and symptoms of vegetative dysfunction typical of micromercurialism: depressing, apathy, trembling hands, etc.

From the preceding descriptions it is evident that neurotic symptoms of heightened emotional lability predominate.

Vegetative disorders expressed as headaches, pain in the vicinity of the heart, increased sweating, metallic taste in the mouth, are often accompanied by pulse lability, vascular asymmetry, cardiovascular insufficiency reactions in ortho and klinostatic reflexes, inadequate eye-heart reflexes and sharp irruptive dermographism.

In more advanced states asthenia and progressive neurotic phenomena appear. There is a drop off in fulfillment of ordinary work, complaint of sleepless nights and daytime drowsiness, often accompanied by spasms, inadequate response to injury and poor self image, especially with respect to minor changes in working conditions. These are associated with hand tremors under stress and when attempting fine work.

These clinical, physiological and experimental data indicate that early functional-dynamic disturbances involve changes in cortical neurodynamics, having a phasic character.

The first phase is characterized by destruction of strength and equilibrium of basic neural processes through weakening of the inhibitory and relative predominance of the excitatory process with the simultaneous weakening of the cortical influence on the subcortical region. This results in heightened excitability of the vegetative nervous system, especially its sympathetic region, which is extremely symptomatic of the first phase, being basically one of weakened inhibitory processes.

In the second phase, there is a gradual increase in exhaustibility of cortical cells, vegetative-vascular reactions become inert, testifying to the predominance of inhibition processes. This appears to be the result of weakness in the higher branches of the brain which protects the more reactive parts of the central nervous system.

The syndrome known as mercury erethism involves peculiar disruption of the emotional sphere, and in the light of modern opinion, arises as a result of destruction of the complex interactions between the cortex and the optic thalami producing a neurosis caused by sharp weakening of cortical processes.

Micromercurialism is characterized by a prolonged retention of the phase of augmented cortical excitation with concomitant pathological lability of the vegetative nervous system. Transition into the second phase comes in the later stages of intoxication. significant in the differential diagnosis of micromercurialism are: sleep and emotional disturbances, marred vegetative disorders, tremors and increased salivation.

These specific symptoms are relative. In connection with these accurate analysis of anamnestic and clinical data, working conditions and type of work is necessary for the correct diagnosis of micromercurialism. The mercury etiology of micromercurialism is confirmed by the presence in excrements (usually in the urine) of mercury, the content of which increases under the influence of unithiol.

Note another criterion, the explanation of which is necessary in establishing the etiology of the observed shifts and disturbances. We already stressed that along with the asthenic-vegetative syndrome of mercury etiology, symptoms may be caused not only by toxic action but by various infectious diseases, most of all influenza. In this, however, nervous system changes, as a rule, develop quickly, soon after the fall in temperature, and disappearance of catarrh, and then gradually level off. In micromercurialism vegetative dystonia and asthenia develop slowly, by degrees, gradually increasing in their intensity.

From clinical and statistical materials presented by us based on periodic investigations and special observations, clinical data, obtained under hospital conditions, suggests that in "non-specific" syndromes in persons having contact with low concentration of mercury, there are "specific" elements permitting interpretation of the syndrome as a phenomenon of micromercurialism.



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