486
While analysis of the amniotic fluid provides valuable information in some conditions there is sufficient cause for concern about its safety to limit its usefulness for the time being. Possibly the prior localisation of the placenta by ultrasound may prove to be unnecessary, but we still need to know the actual risk of rhesus sensitisation and to obtain more extensive experience with suprapubic amniocentesis in late pregnancy. Gerbie, A B, Nadler, H L, and Gerbie, M V, American Journal of Obstetrics and Gynecology, 1971, 109, 765. 2 Kalbac, R W, and Newman, R L, Obstetrics and Gynecology, 1974, 44, 814. 3 Fairweather, D V I, in Amniotic Fluid, p 19, ed D V I Fairweather and T K A B Eskes. Amsterdam, Excerpta Medica, 1973. 4 Miskin, M, et al, Obstetrics and Gynecology, 1974, 43, 872. Curtis, J D, et al, Obstetrics and Gynecology, 1972, 40, 194. 4 Rome, R M, Glover, J I, and Simmons, S C, British Journal of Obstetrics and Gynaecology, 1975, 82, 662. 7 Gordon, H R, and Deukmedjian, A G, American Journal of Obstetrics and Gynecology, 1975, 122, 287. 8Ekgren, J, and Moe, N, Acta Obstetricia et Gynecologica Scandinavica, 1974. 53, 263.
Low-protein diets in chronic renal failure Restriction of dietary protein relieves symptoms of uraemiathe nausea and vomiting in particular. No doubt dietary restriction could postpone the onset of symptoms if started early on, but since their appearance is unpredictable such a policy makes little sense, except perhaps in patients with progressive anaemia. Imposition of an unpalatable diet solely in an imperious attempt to improve the "biochemical profile" is neither reasonable nor kind. Symptoms may be minimised, but sooner or later nutrition suffers. How soon depends partly on the progress of the underlying disease and partly on the singlemindedness with which the patient follows the diet. The chemical identity of the products of protein metabolism which cause the clinical syndrome of uraemia remains as elusive as ever, but it is important to realise that the poor nutrition of uraemic patients may as often be caused by an inadequate diet as by the toxic effects of retained compounds.' A low-protein diet does not improve renal function; it only reduces the accumulation of potentially toxic metabolites. The progression of renal insufficiency depends on the nature of the kidney disease; the prevention of saline depletion; and the control of hypertension, urinary tract infection, and a handful of other correctable factors. Doubts remain about the ideal composition of low-protein diets, and patients continue to have considerable difficulty in stomaching them however exemplary their design. Although uraemic patients have maintained nitrogen balance on as little as 20 g of protein daily,2-4 many do not easily do so, at least not within a few weeks. Only when about 35 g of protein is allowed can nitrogen balance be reasonably well assured.5 Not only must the diet contain both high-quality protein to ensure sufficient essential amino-acids and a disproportionately large energy supply as carbohydrate and fat, but the patient needs to be persuaded to eat it. Predictably, the more restricted the diet the poorer is the patient's compliance.6 A low-protein diet postpones the need for regular dialysis or renal transplantation, but it may compromise the success of those treatments if the patient's nutrition deteriorates
BRITISH MEDICAL JOURNAL
29 NOVEMBER 1975
meanwhile. Measurement of nutritional status is infuriatingly imprecise; in the end sequential measurement of body weight (in the absence of oedema) is probably as good as any other variable. Plasma albumin is often moderately reduced, but its concentration conceals the extent to which the extravascular pool has been reduced to maintain the intravascular albumin.7 8 Albumin turnover is low because catabolism is proportional to the intravascular concentration.7 These changes give little information about the adequacy of a diet, for they happen soon after protein is restricted and are not usually progressive.8 Not surprisingly, low-protein diets are most useful in those with very slowly progressive chronic renal failure. More complex treatment may often be postponed indefinitely in patients with chronic renal failure as a result of relieved obstructive nephropathy, healed renal tuberculosis, or chronic pyelonephritis. For these, and for the hard core of patients either unsuitable for or unable to obtain transplantation or dialysis, further refinement of dietary treatment must be pursued. Diets based on essential amino-acids have yet to be proved advantageous, but their keto- or hydroxy-acid precursors have shown initial promise. 9 Originally suggested' 0 for improving nutrition on very restricted renal diets (by channelling retained urea nitrogen into protein synthesis) they seem instead to exert a protein anabolic effect greater than their transamination alone can explain. 9 1' These compounds deserve further study, but for most patients with progressive renal failure conventional diets containing less than 30 g of protein will be used briefly, if at all, as soon as regular dialysis and transplantation become widely available.
1Richards,
P, in Recent Advances in Renal Disease, ed N F Jones, p 152. Edinburgh, Churchill Livingstone, 1975. Giordano, C, J7ournal of Laboratory and Clinical Medicine, 1963, 62, 231. 3 Giovannetti, S, and Maggiore, Q, Lancet, 1964, 1, 1000. 4 Shaw, A B, et al, Quarterly,Journal of Medicine, 1965, 34, 237. 5 Ford, J, et al, British MedicalJrournal, 1969, 1, 735. 6 Sorensen, M K, and Kopple, J D, American Journal of Clinical Nutrition. 1968, 21, 631. 7 Coles, G A, Peters, D K, and Jones, J H, Clinical Science, 1970, 39, 423. 8 Bianchi, R, et al, Nephron, 1975, 15, 409. 9 Walser, M, et al,Jrournal of Clinical Investigation, 1973, 52, 678. '0 Richards, P, et al, Lancet, 1967, 2, 845. 1' Sapir, D G, et al,Journal of Clinical Investigation, 1974, 54, 974. 2
Immunotherapy for multiple sclerosis The perivascular cuffing and oedema seen in acute lesions of multiple sclerosis (MS) suggest that some sort of immune allergic phenomenon may play a part in causing it.' Controlled antibody surveys on patients with MS have thrown suspicion on many viruses, including measles, type C influenza, herpes simplex, parainfluenza 3, mumps, varicella zoster, and vaccinia; any part they may play in the production of the disease process is now under close scrutiny.28 Virions and nucleopsids of parainfluenza and paramyxoviruses have been found in brain tissue from patients with MS by cocultivation techniques and by electronmicroscopy.9-11 During replication some viruses incorporate cell constituents into their new coat, which alter the antigenicity of the new virions and may also modify the antigenicity of the surface of the infected cells. Changing the cellular antigenic determinants in this way might cause neuronal or glial cells to be regarded as "non-self" and so provoke a damaging allergic reaction.
BRITISH MEDICAL JOURNAL
29 NOVEMBER 1975
487
Myelin, which is produced by some glial cells, could be concerned in the process and demyelination result.'2 Both cellmediated immunity and cytogenicity to neural antigens occur in MS;13---15 the level of IgG in the cerebrospinal fluid is frequently raised ;' 6 and a complement-dependent factor in serum has been identified which produces demyelination in vitro.'7 Lance,"8 Jones,"'9 and Knight2 ' and their co-workers have recently studied the effect of combined immunosuppression using corticosteroids, azathioprine, and antilymphocytic globulin (ALG) in 14 patients with MS. In an attempt to annul the immunogenicity of ALG all patients received intravenous infusions of aggregate-free normal horse IgG. The patients were carefully studied and their clinical and immunological reactions observed. Attention was given to the lymphocytic response to phytohaemagglutinin, conconavalin A, and pokeweed mitogen in cases both positive and negative for HLA7. After one year attempts were made to reduce the level of immunosuppression, but in many cases this led to rebound phenomena. The results indicated that during treatment there were fewer than expected relapses and that the severity of these was reduced. Side effects occurred-namely, phlebitis, serum sickness, and non-fatal anaphylactic shock to the ALG-while mild hair loss was attributed to azathioprine and the usual spectrum of non-fatal complications occurred as a result of the steroid treatment. Brendel et a12' 22 and Ring et a123 have also tried a similar treatment with some success. The mean survival of a patient with MS is around 20 years, and in many cases the disease runs a benign course. Statistical assessment of the benefits of treatment is notoriously difficult in this condition. The unanswerable question at the moment is whether or not it will prove possible to identify at the onset patients with a poor prognosis. Immunosuppressive treatment would need to be carried out in a centre well equipped for controlling complex treatment; it does not seem to be warranted in the potentially benign case. Another doubt is how long the immunosuppressive regimen could continue, since the rate of relapse on withdrawal was high. This work has, however, helped to confirm the suggestion that an "auto-aggressive immunological reaction" plays a part in the pathogenesis ofMS. Lumsden, C E, in Handbook of Clinical Neurology, eds A J Vinken and G W Bruyn, New York, Elsevir, 1970, 9, 217. Adams, J M, Neurology, 1967, 17, 707. : Clarke, J K, Dane, D S, and Dick, G W A, Brain, 1965, 88, 953. Caspary, E A, Chambers, M E, and Field, E J, Neurology, 1969, 19, 1038. 5Brody, J A, Lanicet, 1972, 2, 173. Ross, C A C, Lenman, J A R, and Rutter, C, British Medical _Journal, 7
1965, 1, 226. Ross, C A C, Lenman, J A R, and Melville, I D, British
Medical,Journal,
1969, 3, 512. 8 Kapsenberg, J G, Archiovffir die Gesamtite Virzusforschung, 1964, 15, 67. 9 Ter Mculen, V, et ail, Lancet, 1972, 2, 1. Prineas, J, Scie'nice, 1972, 178, 760. Field, E J, et al, Lancet, 1972, 2, 280. ' Webb, H E, in Mid(tiple Sclerosis-Progress in Research, eds E J Field, T M Bell, and P R Carncgie, p 8. Amsterdam, North-Holland, 1972. ': Bartfeld, H, and Atovnatan, T, International Archives of Allergy and Applied Immnunology, 1970, 39, 361. Field, E J, and Caspary, E A, in Muiltiple Sclerosis-Progress in Research, eds E J Field, r M Bell, and P R Carnegie, p 51. Amsterdam, NorthHolland, 1972. 15 Halpern, B, Bakouche, P, and Martial-Lasfarguies, L, Presse Medicale, 1969, 77, 2103. Tourtelotte, W W, in Muiltiple Sclerosis-Imnltitiology Virology and Ultrastrlctuire, eds F Wolfgram, G W Ellison, J G Stevens and J M Andrews. New York, Academic Press, 1972, 285. 17 Bornstein, M B, National Cancer Instituite Monographs, 1963, 11, 197. 18 Lance, E M, et al, Clinical and 1975, 21, 1. 1975, 21, 13. 19 Jones, V E, et al, 1975, 21, 23. 2() Knight, S C, et al, Clinical and 21 Brendel, W, et al, Behring Mitteilungen, 1972, 51, 176. 22 Brendel, W, Siefert, J, and Lob, G, Proceedings of the Royal Society of Medicine, 1972, 65, 531. 23 Ring, J, et al, Lancet, 1974, 2, 1093.
Experim2ental Imtmulznology, Clinlical anld Experimtental Immultnology, Experimlental Immutnnology, Inlstitute
Great expectations from proximal vagotomy Progress in the surgical treatment of duodenal ulcer has been punctuated by excitements and disappointments. Almost every new procedure has aroused great expectations, with very favourable results reported in selected series of patients; but it is rare for the optimism to be maintained. In recent years a new star has appeared: proximal gastric vagotomy. Considerable claims have been, and are being made, for the superiority of this operation-but older surgeons, who have lived through several changes of fashion, will require convincing evidence before they abandon any procedure which in their own hands yields good results. In 1968 the Leeds trial' of the then conventional methods of surgical treatment showed that very careful objective assessment was required before any definite conclusions could be reached about the results of surgery for duodenal ulcer. The reporting of the results obtained by using a particular operation in selected patients may produce both biased and erroneous ideas of the value of that procedure Three criteria may be used to judge the results of peptic ulcer surgery: firstly, the risk to life of effective surgical treatment; secondly, the incidence of residual gastrointestinal symptoms; and, thirdly, the risk of late nutritional deficiencies. The risk of effective surgical treatment includes not only the risk of the primary operation but also the recurrent ulcer rate. If a substantial number of patients require a second operation to control their ulcer diathesis then the morbidity and mortality rate of the second procedure has to be included in the
reckoning. The immediate risk of proximal vagotomy is low (0 30O in a collected series2 of over 5000 operations from 40 centres). One or two instances of necrosis of the lesser curve of the stomach have been reported, and this seems to be a rare but definite complication peculiar to this operation. The incidence of recurrent ulceration is, however, more difficult to assess. In most series it is 1ow2-4 (less than 5%) but there have been two small series5 6 with recurrent ulcer rates of over 20%. Recurrent ulceration is almost certainly related to the effectiveness with which acid secretion is controlled. After proximal gastric vagotomy, secretion tests show an initial reduction of acid comparable with other types of vagotomy, but over the first year after operation a, distinct rise is usually observed in basal, maximal, and insulin-stimulated secretion. Recently the results have been published7 of acid secretion tests in 21 patients measured at least five years after proximal vagotomy: basal secretion was still reduced by 79% and peak acid responses to pentagastrin by 48%. It seems, then, that after the slight rebound which occurs within the first year the operation produces a stable reduction of acid secretion by the stomach. The incidence of postoperative gastrointestinal disturbance is minimal. Many of the common disturbances seen after gastric surgery such as dumping and bile vomiting are almost certainly related to the bypass, destruction, or resection of the normal mechanisms of gastric emptying. As the disturbance of gastric emptying is made minimal in proximal gastric vagotomy such symptoms should be uncommon. This is confirmed by most of the published series. Particularly important are the results of a controlled trial reported8 from Belfast, in which proximal vagotomy in 50 patients produced statistically better symptomatic results than selective vagotomy and gastroenterostomy in a comparable group of 50 patients.
While analysis of the amniotic fluid provides valuable information in some conditions there is sufficient cause for concern about its safety to limit its usefulness for the time being. Possibly the prior localisation of the placenta by ultrasound may prove to be unnecessary, but we still need to know the actual risk of rhesus sensitisation and to obtain more extensive experience with suprapubic amniocentesis in late pregnancy. Gerbie, A B, Nadler, H L, and Gerbie, M V, American Journal of Obstetrics and Gynecology, 1971, 109, 765. 2 Kalbac, R W, and Newman, R L, Obstetrics and Gynecology, 1974, 44, 814. 3 Fairweather, D V I, in Amniotic Fluid, p 19, ed D V I Fairweather and T K A B Eskes. Amsterdam, Excerpta Medica, 1973. 4 Miskin, M, et al, Obstetrics and Gynecology, 1974, 43, 872. Curtis, J D, et al, Obstetrics and Gynecology, 1972, 40, 194. 4 Rome, R M, Glover, J I, and Simmons, S C, British Journal of Obstetrics and Gynaecology, 1975, 82, 662. 7 Gordon, H R, and Deukmedjian, A G, American Journal of Obstetrics and Gynecology, 1975, 122, 287. 8Ekgren, J, and Moe, N, Acta Obstetricia et Gynecologica Scandinavica, 1974. 53, 263.
Low-protein diets in chronic renal failure Restriction of dietary protein relieves symptoms of uraemiathe nausea and vomiting in particular. No doubt dietary restriction could postpone the onset of symptoms if started early on, but since their appearance is unpredictable such a policy makes little sense, except perhaps in patients with progressive anaemia. Imposition of an unpalatable diet solely in an imperious attempt to improve the "biochemical profile" is neither reasonable nor kind. Symptoms may be minimised, but sooner or later nutrition suffers. How soon depends partly on the progress of the underlying disease and partly on the singlemindedness with which the patient follows the diet. The chemical identity of the products of protein metabolism which cause the clinical syndrome of uraemia remains as elusive as ever, but it is important to realise that the poor nutrition of uraemic patients may as often be caused by an inadequate diet as by the toxic effects of retained compounds.' A low-protein diet does not improve renal function; it only reduces the accumulation of potentially toxic metabolites. The progression of renal insufficiency depends on the nature of the kidney disease; the prevention of saline depletion; and the control of hypertension, urinary tract infection, and a handful of other correctable factors. Doubts remain about the ideal composition of low-protein diets, and patients continue to have considerable difficulty in stomaching them however exemplary their design. Although uraemic patients have maintained nitrogen balance on as little as 20 g of protein daily,2-4 many do not easily do so, at least not within a few weeks. Only when about 35 g of protein is allowed can nitrogen balance be reasonably well assured.5 Not only must the diet contain both high-quality protein to ensure sufficient essential amino-acids and a disproportionately large energy supply as carbohydrate and fat, but the patient needs to be persuaded to eat it. Predictably, the more restricted the diet the poorer is the patient's compliance.6 A low-protein diet postpones the need for regular dialysis or renal transplantation, but it may compromise the success of those treatments if the patient's nutrition deteriorates
BRITISH MEDICAL JOURNAL
29 NOVEMBER 1975
meanwhile. Measurement of nutritional status is infuriatingly imprecise; in the end sequential measurement of body weight (in the absence of oedema) is probably as good as any other variable. Plasma albumin is often moderately reduced, but its concentration conceals the extent to which the extravascular pool has been reduced to maintain the intravascular albumin.7 8 Albumin turnover is low because catabolism is proportional to the intravascular concentration.7 These changes give little information about the adequacy of a diet, for they happen soon after protein is restricted and are not usually progressive.8 Not surprisingly, low-protein diets are most useful in those with very slowly progressive chronic renal failure. More complex treatment may often be postponed indefinitely in patients with chronic renal failure as a result of relieved obstructive nephropathy, healed renal tuberculosis, or chronic pyelonephritis. For these, and for the hard core of patients either unsuitable for or unable to obtain transplantation or dialysis, further refinement of dietary treatment must be pursued. Diets based on essential amino-acids have yet to be proved advantageous, but their keto- or hydroxy-acid precursors have shown initial promise. 9 Originally suggested' 0 for improving nutrition on very restricted renal diets (by channelling retained urea nitrogen into protein synthesis) they seem instead to exert a protein anabolic effect greater than their transamination alone can explain. 9 1' These compounds deserve further study, but for most patients with progressive renal failure conventional diets containing less than 30 g of protein will be used briefly, if at all, as soon as regular dialysis and transplantation become widely available.
1Richards,
P, in Recent Advances in Renal Disease, ed N F Jones, p 152. Edinburgh, Churchill Livingstone, 1975. Giordano, C, J7ournal of Laboratory and Clinical Medicine, 1963, 62, 231. 3 Giovannetti, S, and Maggiore, Q, Lancet, 1964, 1, 1000. 4 Shaw, A B, et al, Quarterly,Journal of Medicine, 1965, 34, 237. 5 Ford, J, et al, British MedicalJrournal, 1969, 1, 735. 6 Sorensen, M K, and Kopple, J D, American Journal of Clinical Nutrition. 1968, 21, 631. 7 Coles, G A, Peters, D K, and Jones, J H, Clinical Science, 1970, 39, 423. 8 Bianchi, R, et al, Nephron, 1975, 15, 409. 9 Walser, M, et al,Jrournal of Clinical Investigation, 1973, 52, 678. '0 Richards, P, et al, Lancet, 1967, 2, 845. 1' Sapir, D G, et al,Journal of Clinical Investigation, 1974, 54, 974. 2
Immunotherapy for multiple sclerosis The perivascular cuffing and oedema seen in acute lesions of multiple sclerosis (MS) suggest that some sort of immune allergic phenomenon may play a part in causing it.' Controlled antibody surveys on patients with MS have thrown suspicion on many viruses, including measles, type C influenza, herpes simplex, parainfluenza 3, mumps, varicella zoster, and vaccinia; any part they may play in the production of the disease process is now under close scrutiny.28 Virions and nucleopsids of parainfluenza and paramyxoviruses have been found in brain tissue from patients with MS by cocultivation techniques and by electronmicroscopy.9-11 During replication some viruses incorporate cell constituents into their new coat, which alter the antigenicity of the new virions and may also modify the antigenicity of the surface of the infected cells. Changing the cellular antigenic determinants in this way might cause neuronal or glial cells to be regarded as "non-self" and so provoke a damaging allergic reaction.
BRITISH MEDICAL JOURNAL
29 NOVEMBER 1975
487
Myelin, which is produced by some glial cells, could be concerned in the process and demyelination result.'2 Both cellmediated immunity and cytogenicity to neural antigens occur in MS;13---15 the level of IgG in the cerebrospinal fluid is frequently raised ;' 6 and a complement-dependent factor in serum has been identified which produces demyelination in vitro.'7 Lance,"8 Jones,"'9 and Knight2 ' and their co-workers have recently studied the effect of combined immunosuppression using corticosteroids, azathioprine, and antilymphocytic globulin (ALG) in 14 patients with MS. In an attempt to annul the immunogenicity of ALG all patients received intravenous infusions of aggregate-free normal horse IgG. The patients were carefully studied and their clinical and immunological reactions observed. Attention was given to the lymphocytic response to phytohaemagglutinin, conconavalin A, and pokeweed mitogen in cases both positive and negative for HLA7. After one year attempts were made to reduce the level of immunosuppression, but in many cases this led to rebound phenomena. The results indicated that during treatment there were fewer than expected relapses and that the severity of these was reduced. Side effects occurred-namely, phlebitis, serum sickness, and non-fatal anaphylactic shock to the ALG-while mild hair loss was attributed to azathioprine and the usual spectrum of non-fatal complications occurred as a result of the steroid treatment. Brendel et a12' 22 and Ring et a123 have also tried a similar treatment with some success. The mean survival of a patient with MS is around 20 years, and in many cases the disease runs a benign course. Statistical assessment of the benefits of treatment is notoriously difficult in this condition. The unanswerable question at the moment is whether or not it will prove possible to identify at the onset patients with a poor prognosis. Immunosuppressive treatment would need to be carried out in a centre well equipped for controlling complex treatment; it does not seem to be warranted in the potentially benign case. Another doubt is how long the immunosuppressive regimen could continue, since the rate of relapse on withdrawal was high. This work has, however, helped to confirm the suggestion that an "auto-aggressive immunological reaction" plays a part in the pathogenesis ofMS. Lumsden, C E, in Handbook of Clinical Neurology, eds A J Vinken and G W Bruyn, New York, Elsevir, 1970, 9, 217. Adams, J M, Neurology, 1967, 17, 707. : Clarke, J K, Dane, D S, and Dick, G W A, Brain, 1965, 88, 953. Caspary, E A, Chambers, M E, and Field, E J, Neurology, 1969, 19, 1038. 5Brody, J A, Lanicet, 1972, 2, 173. Ross, C A C, Lenman, J A R, and Rutter, C, British Medical _Journal, 7
1965, 1, 226. Ross, C A C, Lenman, J A R, and Melville, I D, British
Medical,Journal,
1969, 3, 512. 8 Kapsenberg, J G, Archiovffir die Gesamtite Virzusforschung, 1964, 15, 67. 9 Ter Mculen, V, et ail, Lancet, 1972, 2, 1. Prineas, J, Scie'nice, 1972, 178, 760. Field, E J, et al, Lancet, 1972, 2, 280. ' Webb, H E, in Mid(tiple Sclerosis-Progress in Research, eds E J Field, T M Bell, and P R Carncgie, p 8. Amsterdam, North-Holland, 1972. ': Bartfeld, H, and Atovnatan, T, International Archives of Allergy and Applied Immnunology, 1970, 39, 361. Field, E J, and Caspary, E A, in Muiltiple Sclerosis-Progress in Research, eds E J Field, r M Bell, and P R Carnegie, p 51. Amsterdam, NorthHolland, 1972. 15 Halpern, B, Bakouche, P, and Martial-Lasfarguies, L, Presse Medicale, 1969, 77, 2103. Tourtelotte, W W, in Muiltiple Sclerosis-Imnltitiology Virology and Ultrastrlctuire, eds F Wolfgram, G W Ellison, J G Stevens and J M Andrews. New York, Academic Press, 1972, 285. 17 Bornstein, M B, National Cancer Instituite Monographs, 1963, 11, 197. 18 Lance, E M, et al, Clinical and 1975, 21, 1. 1975, 21, 13. 19 Jones, V E, et al, 1975, 21, 23. 2() Knight, S C, et al, Clinical and 21 Brendel, W, et al, Behring Mitteilungen, 1972, 51, 176. 22 Brendel, W, Siefert, J, and Lob, G, Proceedings of the Royal Society of Medicine, 1972, 65, 531. 23 Ring, J, et al, Lancet, 1974, 2, 1093.
Experim2ental Imtmulznology, Clinlical anld Experimtental Immultnology, Experimlental Immutnnology, Inlstitute
Great expectations from proximal vagotomy Progress in the surgical treatment of duodenal ulcer has been punctuated by excitements and disappointments. Almost every new procedure has aroused great expectations, with very favourable results reported in selected series of patients; but it is rare for the optimism to be maintained. In recent years a new star has appeared: proximal gastric vagotomy. Considerable claims have been, and are being made, for the superiority of this operation-but older surgeons, who have lived through several changes of fashion, will require convincing evidence before they abandon any procedure which in their own hands yields good results. In 1968 the Leeds trial' of the then conventional methods of surgical treatment showed that very careful objective assessment was required before any definite conclusions could be reached about the results of surgery for duodenal ulcer. The reporting of the results obtained by using a particular operation in selected patients may produce both biased and erroneous ideas of the value of that procedure Three criteria may be used to judge the results of peptic ulcer surgery: firstly, the risk to life of effective surgical treatment; secondly, the incidence of residual gastrointestinal symptoms; and, thirdly, the risk of late nutritional deficiencies. The risk of effective surgical treatment includes not only the risk of the primary operation but also the recurrent ulcer rate. If a substantial number of patients require a second operation to control their ulcer diathesis then the morbidity and mortality rate of the second procedure has to be included in the
reckoning. The immediate risk of proximal vagotomy is low (0 30O in a collected series2 of over 5000 operations from 40 centres). One or two instances of necrosis of the lesser curve of the stomach have been reported, and this seems to be a rare but definite complication peculiar to this operation. The incidence of recurrent ulceration is, however, more difficult to assess. In most series it is 1ow2-4 (less than 5%) but there have been two small series5 6 with recurrent ulcer rates of over 20%. Recurrent ulceration is almost certainly related to the effectiveness with which acid secretion is controlled. After proximal gastric vagotomy, secretion tests show an initial reduction of acid comparable with other types of vagotomy, but over the first year after operation a, distinct rise is usually observed in basal, maximal, and insulin-stimulated secretion. Recently the results have been published7 of acid secretion tests in 21 patients measured at least five years after proximal vagotomy: basal secretion was still reduced by 79% and peak acid responses to pentagastrin by 48%. It seems, then, that after the slight rebound which occurs within the first year the operation produces a stable reduction of acid secretion by the stomach. The incidence of postoperative gastrointestinal disturbance is minimal. Many of the common disturbances seen after gastric surgery such as dumping and bile vomiting are almost certainly related to the bypass, destruction, or resection of the normal mechanisms of gastric emptying. As the disturbance of gastric emptying is made minimal in proximal gastric vagotomy such symptoms should be uncommon. This is confirmed by most of the published series. Particularly important are the results of a controlled trial reported8 from Belfast, in which proximal vagotomy in 50 patients produced statistically better symptomatic results than selective vagotomy and gastroenterostomy in a comparable group of 50 patients.
