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FOOD ADDITIVES
887
toxicosis could be predicted by the detection of L.A.T.S. in maternal serum and cord blood. This is a further example of an in-vitro test which may prove very useful in management of thyrotoxicosis during pregnancy and in the immediate post-partum period. Probably all but the most obdurate cases of thyrotoxicosis in pregnancy could be adequately controlled by medical treatment, but this depends, at least partly, on the availability of various hormoneUnfortunately, as with other assay techniques. endocrinological problems,2O the gap between what is possible and what is available is still discouragingly wide, and the extent of this gap may to some extent determine the management of an individual case. ELECTRICAL STIMULATION OF THE BLADDER AN annotation seven years ago$1 reviewed early clinical experiments with electrical stimulation of the bladder in paraplegia. Limited success had been reported in a few cases using an implanted receiverstimulator with multiple electrodes on the detrusor. Problems included dislocation and fracture of the electrodes, as well as spread of the current causing pain or contraction of the pelvic-floor musclesparticularly the external urethral sphincter. It was concluded that if the formidable technical difficulties could be overcome there might be worth-while clinical advantages in terms of preservation of renal function and continence. Since that time reported progress has been disappointingly, if not surprisingly, slow. Bors and Comarr 222 found about thirty -published cases of direct bladder stimulation, with long-term success in only three, of whom one had required a subarachnoid alcohol block and another a pudendal neurectomy for relief of external-sphincter obstruction. In an effort to eliminate the spasm responsible for this troublesome complication, Cartensen et al.23 have attempted to fatigue the perineal muscles by tetanic stimulation immediately before the induction of a bladder contraction. Experiments have been carried out in dogs and monkeys, but the results were promising only in the
monkeys. Dissatisfaction with the technique of the direct approach has led to attempts to produce bladder contraction by stimulation of the sacral parasympathetic pathways at various levels. Habib 24 found that unilateral stimulation of the second sacral nerve in man caused only clonic muscular contractions in the legs. Stimulation of the third sacral nerve, however, caused detrusor contraction, as well as penile erection and spasm of the external urethral and anal sphincters. The sphincter spasm did not prevent voiding. Using the fourth sacral nerve, there was better voiding, with terminal erection which was not so sustained. In two
paraplegics 20. 21. 22. 23. 24.
the bladder
was
emptied satisfactorily
in
Anderson, J., et al. Lancet, 1972, i, 95. ibid. 1965, i, 851. Bors, E., Comarr, A. E. Neurological Urology. New York, 1971. Cartensen, H. E., Freed, P. S., Molony, D. A., Kantrowitz, A. Invest. Urol. 1970, 7, 387. Habib, H. N. in The Neurogenic Bladder (edited by S. Boyarski).
Baltimore,
1966.
this way for four months, before sepsis necessitated the removal of the percutaneous electrodes. Reports are still awaited on the use of an implantable stimulator for nerve-root application, and meanwhile Nashold et al. 25 have described such a system with the electrodes implanted in the Si-s region of the conus medullaris. In three out of four patients with suprasacral lesions, satisfactory voiding had been achieved for periods of two, six, and eight months, though only following partial division of the external sphincter in the two Undesirable side-effects had included leg males. movements, penile erection, and ejaculation, and, perhaps surprisingly, sympathetic activity which in one case led to headache from hypertension. These complications are said to be largely controllable by varying the frequency and voltage of the current; simultaneous defalcation occurred occasionally in the two males and always in the female. As Nashold and colleagues comment, " the surgical procedure is still experimental and requires further evaluation before it can be recommended for general use ". It seems clear that, in the foreseeable future, much more will be gained in paraplegia from improvements in the application of standard surgical techniques than from electrical stimulation of the bladder, which should probably be carried out only in a few well-placed institutions and on an experimental basis. FOOD ADDITIVES THE fifteenth F.A.O./W.H.O. report on food additives 26 is concerned with additives in baby foods, and with enzymes, chemically modified starches, and some other chemicals. The food industry’s technologists
produce new additives, and the committee dutifully ponders on their safety. They are experienced men, so, within the conventions of toxicology, the answers are sensible. But basic questions of food and health are rarely mentioned. Baby foods and their additives are a concern of the affluent, in whom the major nutritional problem is obesity; what is the role of these baby foods and their promotion in development of obesity ? Enzymes obtained from edible parts of animals or plants are regarded by the Expert Committee as foods, and therefore not as additives, but clearly many active toxic compounds can be extracted and concentrated from normal foods (e.g., oxalic acid from spinach). We know from drug toxicity studies that animal tests are very imperfect indicators of human toxicity; only clinical experience and careful control of the introduction of new drugs can tell us about their real dangers. In one known case where a food additive was implicated in disease-an outbreak of exudative erythema multiforme 27-it was only the unusual nature of the epidemic that brought the connection to light. No routine epidemiological studies are made to find out if food additives are toxic. Perhaps the Expert Committee should stop accepting the conventions and press for a start to the large-scale research programmes that are needed. 25. Nashold, B. S., Jr., Friedman, H., Glenn, J. F., Grimes, J. H., Barry, W. F., Avery, R. Archs Surg. 1972, 104, 195. 26. Joint F.A.O./W.H.O. Expert Committee on Food Additives, Wld Hlth Org. tech. Rep. Ser. 1972, no. 488. 40p; $1.00. 27. Fd Cosmet. Toxicol. 1963, 1, 92.
toxicosis could be predicted by the detection of L.A.T.S. in maternal serum and cord blood. This is a further example of an in-vitro test which may prove very useful in management of thyrotoxicosis during pregnancy and in the immediate post-partum period. Probably all but the most obdurate cases of thyrotoxicosis in pregnancy could be adequately controlled by medical treatment, but this depends, at least partly, on the availability of various hormoneUnfortunately, as with other assay techniques. endocrinological problems,2O the gap between what is possible and what is available is still discouragingly wide, and the extent of this gap may to some extent determine the management of an individual case. ELECTRICAL STIMULATION OF THE BLADDER AN annotation seven years ago$1 reviewed early clinical experiments with electrical stimulation of the bladder in paraplegia. Limited success had been reported in a few cases using an implanted receiverstimulator with multiple electrodes on the detrusor. Problems included dislocation and fracture of the electrodes, as well as spread of the current causing pain or contraction of the pelvic-floor musclesparticularly the external urethral sphincter. It was concluded that if the formidable technical difficulties could be overcome there might be worth-while clinical advantages in terms of preservation of renal function and continence. Since that time reported progress has been disappointingly, if not surprisingly, slow. Bors and Comarr 222 found about thirty -published cases of direct bladder stimulation, with long-term success in only three, of whom one had required a subarachnoid alcohol block and another a pudendal neurectomy for relief of external-sphincter obstruction. In an effort to eliminate the spasm responsible for this troublesome complication, Cartensen et al.23 have attempted to fatigue the perineal muscles by tetanic stimulation immediately before the induction of a bladder contraction. Experiments have been carried out in dogs and monkeys, but the results were promising only in the
monkeys. Dissatisfaction with the technique of the direct approach has led to attempts to produce bladder contraction by stimulation of the sacral parasympathetic pathways at various levels. Habib 24 found that unilateral stimulation of the second sacral nerve in man caused only clonic muscular contractions in the legs. Stimulation of the third sacral nerve, however, caused detrusor contraction, as well as penile erection and spasm of the external urethral and anal sphincters. The sphincter spasm did not prevent voiding. Using the fourth sacral nerve, there was better voiding, with terminal erection which was not so sustained. In two
paraplegics 20. 21. 22. 23. 24.
the bladder
was
emptied satisfactorily
in
Anderson, J., et al. Lancet, 1972, i, 95. ibid. 1965, i, 851. Bors, E., Comarr, A. E. Neurological Urology. New York, 1971. Cartensen, H. E., Freed, P. S., Molony, D. A., Kantrowitz, A. Invest. Urol. 1970, 7, 387. Habib, H. N. in The Neurogenic Bladder (edited by S. Boyarski).
Baltimore,
1966.
this way for four months, before sepsis necessitated the removal of the percutaneous electrodes. Reports are still awaited on the use of an implantable stimulator for nerve-root application, and meanwhile Nashold et al. 25 have described such a system with the electrodes implanted in the Si-s region of the conus medullaris. In three out of four patients with suprasacral lesions, satisfactory voiding had been achieved for periods of two, six, and eight months, though only following partial division of the external sphincter in the two Undesirable side-effects had included leg males. movements, penile erection, and ejaculation, and, perhaps surprisingly, sympathetic activity which in one case led to headache from hypertension. These complications are said to be largely controllable by varying the frequency and voltage of the current; simultaneous defalcation occurred occasionally in the two males and always in the female. As Nashold and colleagues comment, " the surgical procedure is still experimental and requires further evaluation before it can be recommended for general use ". It seems clear that, in the foreseeable future, much more will be gained in paraplegia from improvements in the application of standard surgical techniques than from electrical stimulation of the bladder, which should probably be carried out only in a few well-placed institutions and on an experimental basis. FOOD ADDITIVES THE fifteenth F.A.O./W.H.O. report on food additives 26 is concerned with additives in baby foods, and with enzymes, chemically modified starches, and some other chemicals. The food industry’s technologists
produce new additives, and the committee dutifully ponders on their safety. They are experienced men, so, within the conventions of toxicology, the answers are sensible. But basic questions of food and health are rarely mentioned. Baby foods and their additives are a concern of the affluent, in whom the major nutritional problem is obesity; what is the role of these baby foods and their promotion in development of obesity ? Enzymes obtained from edible parts of animals or plants are regarded by the Expert Committee as foods, and therefore not as additives, but clearly many active toxic compounds can be extracted and concentrated from normal foods (e.g., oxalic acid from spinach). We know from drug toxicity studies that animal tests are very imperfect indicators of human toxicity; only clinical experience and careful control of the introduction of new drugs can tell us about their real dangers. In one known case where a food additive was implicated in disease-an outbreak of exudative erythema multiforme 27-it was only the unusual nature of the epidemic that brought the connection to light. No routine epidemiological studies are made to find out if food additives are toxic. Perhaps the Expert Committee should stop accepting the conventions and press for a start to the large-scale research programmes that are needed. 25. Nashold, B. S., Jr., Friedman, H., Glenn, J. F., Grimes, J. H., Barry, W. F., Avery, R. Archs Surg. 1972, 104, 195. 26. Joint F.A.O./W.H.O. Expert Committee on Food Additives, Wld Hlth Org. tech. Rep. Ser. 1972, no. 488. 40p; $1.00. 27. Fd Cosmet. Toxicol. 1963, 1, 92.