- Email: [email protected]
COST OF THE HOSPITAL SERVICE
55 PROTEIN-LOSING ENTEROPATHY IN THE SPRUE SYNDROME
incredible that Naimark et al. encountered severe headache only once in treating 15 patients with 200 mg. a day. My experience is that it is preferable to start with one (50 mg.) tablet a day and increase if possible to four.
SIR,-The paper by Dr. Parkins (Dec. 24) is of greal interest because it serves further to lengthen the list oj gastrointestinal conditions in which internal plasmaprotein loss may occur. To his series of 11 cases may be added that of a 39-year-old woman, observed at the National Institutes of Health, suffering from glutensensitive enteropathy.
Chase Farm
Hospital, Enfield,
THOMAS SIMPSON.
Middlesex.
COST OF THE HOSPITAL SERVICE
SIR,-Dr. Terry (Dec. 24) should accept with more caution what he reads in the daily newspapers. The belief that there has been an alarming rise in the cost of the Hospital Service ", though widely accepted, is false. In the last decade cash expenditure on the hospitals has risen steadily, but meanwhile the share of the nation’s resources going to them has in fact declined slightly. As the nation has become more prosperous, the hospitals have lagged behind. Where is the rise, and what is
She had a serum-albumin level of 2-2 g. per 100 ml., and excreted 3-4% of a test dose of 1311-polyvinylpyrrolidone (P.v.p.) in the fxces. Because of the appearance of her jejunal biopsy, a gluten-free diet was prescribed. Follow-up information obtained through her own physician, Dr. Hershel Jick; reveals that her symptoms have been relieved, and a serum sample which he provided yielded an albumin value of 3-5 g. per 100 ml. This is a low normal value by the method employed here.1 It is not sufficiently appreciated that successive batches of P.V.P., due to differences in molecular-weight distribution, may vary considerably with respect to their persistence in the blood, and to the rates of their urinary and faecal
"
alarming about it ? The use of funds by hospitals in Britain is undoubtedly inefficient. To improve efficiency, however, will not make them cheaper-it will make them better hospitals. Similarly, the suggestions put forward by Dr. Terry in his letter would not reduce the cost of hospitals-they would improve the quality of general practice.
J. R. SEALE. BLOOD-CHOLESTEROL AND ASPIRIN SIR,-The effect of salicylates on cholesterol is mentioned in Savill’s System of Clinical Medicine (13th ed.. 1950): Sodium salicylate... increases the excretion oj bile salts and cholesterol " and it is claimed that this is related to work by Schmidt et al. in 1938.1 Would increased excretion of cholesterol be accompanied by increased speed of turnover of steroids, so that this explains the similarity of effect of salicylates and steroids in rheumatism ? Salicylates are excreted as conjugates with glucuronic acid in the urine and the reduction of cholesterol may be related to the increased production of glucuronic acid. "
Since the communication by Dr. Eidlitz (Nov. 19), a male senior technician (A) and I (B) have taken 5 tablets of aspirin daily for 2 weeks (gr. 25 daily). Results: Serum-cholesterol Original 1 week Ist wee k week k 2and week 2nd (mg. per 100 ml.)
level
A B
190 250
We
205 235
185 205
method of estimation which is reproducible to of Rosenthal’s colour reagent as level of cholesterol in my serum has been 250 mg. per 100 ml. regularly and has been used as a check on laboratory accuracy together with a ’Chemtrol’ standard. Previously, we had tested the effect of ascorbic acid 500 mg. per day for 10 days on eight normal and two abnormal people (three males and seven females). Ascorbic acid is highly unsaturated and contains three double bonds. In this small series (cholesterol values between 330 and 150 mg. per 100 ml.) there was no marked difference, except in my case where the post-test level dropped to 210 from an original 250 mg. per 100 ml. In four of the females there was a drop of 20 mg. per 100 ml. Perhaps salicylates may be of benefit in preventing gallbladder dysfunction, especially in pregnancy. The few tests I have done so far seem to indicate that the cholesterol levels are more easily influenced in females than males, and it would be interesting to know the sex in the series described by Dr. Eidlitz. use a
10%, using a modification described by Leffler.2 The
PHYLLIS DAGNALL. 1. 2.
Amer. J. dig. Dis. 1938, 5, 613. Leffler, H. H. Amer. J. clin. Path. 1959, 31, 310.
excretion. Valuable data on the biological behaviour of function of molecular weight are given by Ravin et al .2 P.v.p. as a
Dr. Parkins noted that none of his 10 normal subjects excreted more than 1 % of an intravenous dose of 131I-p.V.p. in the fxces. This finding agrees exactly with my own experience with the preparation which he was using. The supply of polymer used for the preparation of 131I-p.v.p. for my initial studies1 having been exhausted, it was necessary late in 1959 to prepare a new batch, and it was this material which was provided for Dr. Parkins’ use. Thus it is necessary to consider his case 2 to have yielded an abnormal result on the P.v.p. test. I am concerned about his case 9, however, since the P.v.p. excretion seems unduly high, especially in the face of a high serumalbumin level. One wonders whether this patient, a baby girl, might not have succeeded in contaminating the fxcal samples with some radioactive urine. Finally, a comment on his failure to find a correlation between P.v.p. excretion and serum-albumin levels seems appropriate. Since the sprue syndrome may show spontaneous fluctuations in severity, it may be that the intestinal protein loss associated with it is an intermittent, and not a constant, process. If so, the serum-albumin level should reflect the balance between synthesis and degradation or loss, averaged over a period of many days. The P.V.P. test, on the other hand, serves as an index of the protein loss on the day of the injection. The rapid disappearance of P.v.p. from the blood2 would lead one to expect this relationship, and it is borne out by our experience with 2 patients with abnormal P.v.p. excretion and diarrhoea. In each of these, stools were counted on a daily basis, with the result that more than 70% of the total faecal output was accomplished on the first day. Thus, with a disease causing intermittent internal plasma-protein loss, the results of repeated P.v.p. tests should be expected to vary widely, and their correlation with serum-albumin levels might be very poor, even if additional factors such as malnutrition and impaired protein synthesis did not enter into consideration.
It is my present belief that a single P.v.p. test cannot be used to quantify the severity of internal plasma-protein loss in a given patient. The most important limiting factors are the heterogeneity of the polymer, the fact that its distribution and excretion in vivo do not correspond exactly to those of the plasma-proteins, and the possibility of fluctuations in the severity of the protein loss. It is possible, however, to arrive at a rough, empirical correlation between serum-albumin levels and the results of the P.v.p. test when one surveys a group of patients all of 1. 2.
Gordon, R. S., Jr. Lancet, 1959, i, 325. Ravin, H. A., Seligman, A. M., Fine, J. New Engl. J. Med. 1952, 247, 921.
incredible that Naimark et al. encountered severe headache only once in treating 15 patients with 200 mg. a day. My experience is that it is preferable to start with one (50 mg.) tablet a day and increase if possible to four.
SIR,-The paper by Dr. Parkins (Dec. 24) is of greal interest because it serves further to lengthen the list oj gastrointestinal conditions in which internal plasmaprotein loss may occur. To his series of 11 cases may be added that of a 39-year-old woman, observed at the National Institutes of Health, suffering from glutensensitive enteropathy.
Chase Farm
Hospital, Enfield,
THOMAS SIMPSON.
Middlesex.
COST OF THE HOSPITAL SERVICE
SIR,-Dr. Terry (Dec. 24) should accept with more caution what he reads in the daily newspapers. The belief that there has been an alarming rise in the cost of the Hospital Service ", though widely accepted, is false. In the last decade cash expenditure on the hospitals has risen steadily, but meanwhile the share of the nation’s resources going to them has in fact declined slightly. As the nation has become more prosperous, the hospitals have lagged behind. Where is the rise, and what is
She had a serum-albumin level of 2-2 g. per 100 ml., and excreted 3-4% of a test dose of 1311-polyvinylpyrrolidone (P.v.p.) in the fxces. Because of the appearance of her jejunal biopsy, a gluten-free diet was prescribed. Follow-up information obtained through her own physician, Dr. Hershel Jick; reveals that her symptoms have been relieved, and a serum sample which he provided yielded an albumin value of 3-5 g. per 100 ml. This is a low normal value by the method employed here.1 It is not sufficiently appreciated that successive batches of P.V.P., due to differences in molecular-weight distribution, may vary considerably with respect to their persistence in the blood, and to the rates of their urinary and faecal
"
alarming about it ? The use of funds by hospitals in Britain is undoubtedly inefficient. To improve efficiency, however, will not make them cheaper-it will make them better hospitals. Similarly, the suggestions put forward by Dr. Terry in his letter would not reduce the cost of hospitals-they would improve the quality of general practice.
J. R. SEALE. BLOOD-CHOLESTEROL AND ASPIRIN SIR,-The effect of salicylates on cholesterol is mentioned in Savill’s System of Clinical Medicine (13th ed.. 1950): Sodium salicylate... increases the excretion oj bile salts and cholesterol " and it is claimed that this is related to work by Schmidt et al. in 1938.1 Would increased excretion of cholesterol be accompanied by increased speed of turnover of steroids, so that this explains the similarity of effect of salicylates and steroids in rheumatism ? Salicylates are excreted as conjugates with glucuronic acid in the urine and the reduction of cholesterol may be related to the increased production of glucuronic acid. "
Since the communication by Dr. Eidlitz (Nov. 19), a male senior technician (A) and I (B) have taken 5 tablets of aspirin daily for 2 weeks (gr. 25 daily). Results: Serum-cholesterol Original 1 week Ist wee k week k 2and week 2nd (mg. per 100 ml.)
level
A B
190 250
We
205 235
185 205
method of estimation which is reproducible to of Rosenthal’s colour reagent as level of cholesterol in my serum has been 250 mg. per 100 ml. regularly and has been used as a check on laboratory accuracy together with a ’Chemtrol’ standard. Previously, we had tested the effect of ascorbic acid 500 mg. per day for 10 days on eight normal and two abnormal people (three males and seven females). Ascorbic acid is highly unsaturated and contains three double bonds. In this small series (cholesterol values between 330 and 150 mg. per 100 ml.) there was no marked difference, except in my case where the post-test level dropped to 210 from an original 250 mg. per 100 ml. In four of the females there was a drop of 20 mg. per 100 ml. Perhaps salicylates may be of benefit in preventing gallbladder dysfunction, especially in pregnancy. The few tests I have done so far seem to indicate that the cholesterol levels are more easily influenced in females than males, and it would be interesting to know the sex in the series described by Dr. Eidlitz. use a
10%, using a modification described by Leffler.2 The
PHYLLIS DAGNALL. 1. 2.
Amer. J. dig. Dis. 1938, 5, 613. Leffler, H. H. Amer. J. clin. Path. 1959, 31, 310.
excretion. Valuable data on the biological behaviour of function of molecular weight are given by Ravin et al .2 P.v.p. as a
Dr. Parkins noted that none of his 10 normal subjects excreted more than 1 % of an intravenous dose of 131I-p.V.p. in the fxces. This finding agrees exactly with my own experience with the preparation which he was using. The supply of polymer used for the preparation of 131I-p.v.p. for my initial studies1 having been exhausted, it was necessary late in 1959 to prepare a new batch, and it was this material which was provided for Dr. Parkins’ use. Thus it is necessary to consider his case 2 to have yielded an abnormal result on the P.v.p. test. I am concerned about his case 9, however, since the P.v.p. excretion seems unduly high, especially in the face of a high serumalbumin level. One wonders whether this patient, a baby girl, might not have succeeded in contaminating the fxcal samples with some radioactive urine. Finally, a comment on his failure to find a correlation between P.v.p. excretion and serum-albumin levels seems appropriate. Since the sprue syndrome may show spontaneous fluctuations in severity, it may be that the intestinal protein loss associated with it is an intermittent, and not a constant, process. If so, the serum-albumin level should reflect the balance between synthesis and degradation or loss, averaged over a period of many days. The P.V.P. test, on the other hand, serves as an index of the protein loss on the day of the injection. The rapid disappearance of P.v.p. from the blood2 would lead one to expect this relationship, and it is borne out by our experience with 2 patients with abnormal P.v.p. excretion and diarrhoea. In each of these, stools were counted on a daily basis, with the result that more than 70% of the total faecal output was accomplished on the first day. Thus, with a disease causing intermittent internal plasma-protein loss, the results of repeated P.v.p. tests should be expected to vary widely, and their correlation with serum-albumin levels might be very poor, even if additional factors such as malnutrition and impaired protein synthesis did not enter into consideration.
It is my present belief that a single P.v.p. test cannot be used to quantify the severity of internal plasma-protein loss in a given patient. The most important limiting factors are the heterogeneity of the polymer, the fact that its distribution and excretion in vivo do not correspond exactly to those of the plasma-proteins, and the possibility of fluctuations in the severity of the protein loss. It is possible, however, to arrive at a rough, empirical correlation between serum-albumin levels and the results of the P.v.p. test when one surveys a group of patients all of 1. 2.
Gordon, R. S., Jr. Lancet, 1959, i, 325. Ravin, H. A., Seligman, A. M., Fine, J. New Engl. J. Med. 1952, 247, 921.