VIRAL INFECTIONS AND MULTIPLE SCLEROSIS
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490 meq. per litre, standard bicarbonate 13-6 meq. per litre, Paûz 160 mm. Hg (breathing oxygen by face-mask). 250 meq. bicarbonate was administered, and subsequent blood-gas analysis showed normal values, pH 7-31, PaCÛ2 42 mm. Hg, base excess -2 meq. per litre, PaÛ2 185 mm. Hg. A chest infection developed subsequently, and the patient died on the thirteenth postoperative day. The principle of maintaining an adequate nutritional state in the patient undergoing major surgery has been repeatedly stressed. Aminoacids should be administered to make up protein losses over the period of surgery, and calories are also required to spare protein from catabolism. If no carbohydrate is supplied, ketone bodies are formed from the breakdown of fat which also results in acidosis. The profound metabolic acidosis noted in both these patients was probably precipitated by the transfusion of a large quantity of aminosol/fructose/ethanol. In the immediate postoperative period reserves of alkali are depleted, resulting in severe acid-base instability. The resulting pathophysiological changes may well contribute to suture-line dehiscence and other complications which prejudice survival. St George’s Hospital, London SW1. Royal Hampshire County Hospital, Winchester. J. W. S. RICKETT. D. J. BOWEN. SERUM-THYROTROPHIN AND HYPERCHOLESTEROLÆMIA SIR,-Hypothyroidism is known to be a risk factor for coronary heart-disease (C.H.D.). It has even been suggested that preclinical hypothyroidism is also a risk factor for C.H.D.1 Fowler et al. have indicated that hypercholestero- laemia may precede other evidence of thyroid failure. Since the most sensitive indicator of slight thyroid hypo- function seems to be an increase in serum-thyrotrophin (T.s.H.),3 we compared the serum-T.S.H. levels of a group of 50-year-old men who had hypercholesterolxmia with T.S.H. levels in a control group. The men were screened for C.H.D. risk factors in a study of preventive medicine. A second blood-sample was taken from eighty of those with cholesterol values in the highest decile. One hundred and twenty-seven men from the same population but with cholesterol values below the highest decile acted as controls. The serum from both groups was separated, frozen, and stored. The blood-samples from the controls were taken in the same month as those from the persons with hypercholesterolaemia. The immunoreactive T.S.H. in 01 ml. serum was assayed by a radioimmunosorbent technique 4 using 125I-labelled human pituitary T.S.H. (National Pituitary Agency) and anti-T.S.H. coupled to cyanogen-bromide-activated ’ Sephadex’. The standard (Medical Research Council H.T.S.H. research standard A) was dissolved in serum with undetectable or low levels of T.S.H. The limit of sensitivity was 0-5 units per ml. The cholesterol and the triglycerides were assayed in an isopropanol extract of serum by using a Technicon dual-channel system (N-24A and N-70). The mean values for cholesterol (p < 0’001) and trigly- ceride (p < 0-0025) were significantly higher in the hyper- choIesterolEemic group than in the control group (see accompanying table). There was no significant difference between the serum-T.s.H. levels in the two groups. There was no correlation between the T.s.H. values and the serum- 1. Bastenie, P. A., van Haelst, L., Bonnyns, M., Neve, P., Staquet, M. Lancet, 1971, i, 203. 2. Fowler, P. B. S., Swale, J., Andrews, H. ibid. 1970, ii, 488. 3. Hershman, J. M., Pittman, J. A. New Engl. J. Med. 1971, 285, 997. 4. Wide, L. Acta endocr., Copenh. 1969, suppl. 142, p. 207. BLOOD-LIPIDS (MBAN±S.D.) AND SERUM-T.S.H. VALUES IN PERSONS WITH HYPOCHOLBSTEROLAMIA AND CONTROLS cholesterol values (r=0-ll, P> 0-05). The low T.S.H. values in our study suggest that the frequency of mild hypo- thyroidism in patients with hypercholesterolaemia is very low. Departments of Internal Medicine and Clinical Chemistry, University Hospital, Uppsala, Sweden. H. HEDSTRAND L. WIDE. VIRAL INFECTIONS AND MULTIPLE SCLEROSIS SIR,-Professor Field proposes that in multiple sclerosis (M.s.) persisting viruses may act as adjuvants in an auto- immune attack on myelin. But he and Mr Caspary may have already supplied a more old-fashioned answer to the problem. Measles, for instance, is an acute illness- particularly in the rare form called " black measles". Serum-antibody levels to measles virus are high in auto- immune diseases, chronic active hepatitis, and M.s., but it is still uncertain whether this results from an atypical immune response or to latent measles infection. If the infection occasionally. behaves as a " slow virus ", an additional adjuvant is probably needed to allow it access into the brain. Freund’s complete adjuvant has experi- mentally this effect. Dead mycobacteria 1 may then make the difference between mumps encephalitis, for example, and less dangerous mumps meningitis. An earlier and sustained immune alteration may have initially triggered the sensitised lymphocytes in M.s. In Britain, tuberculosis and more often sarcoidosis are now possibly the culprits. Raised immunity is a feature of sarcoidosis,2 and Caspary and Field 3 showed how wide and prolonged the cell- mediated immunity is in this disease. They also found that only one of our dozen cases of suspected late-stage sarcoidosis 4 failed to show by lymphocyte-sensitisation tests the immunopathology of sarcoidosis. This patient has had myasthenia gravis for 28 years, and her memory- lymphocytes for the event have now probably died. Silent progression of "healed" sarcoidosis may account for many ills: perhaps it may sometimes take a part in the pathogenesis of M.s. Wood Cottage, Chilworth, Surrey. GERALD A. MACGREGOR. RENAL FAILURE OR SIMPLE STARVATION ? SiR,-Dr Kumar and his colleagues 5 report a case of malnutrition as a cause of chronic renal failure. This association, already suggested by Pimstone et aI.,6 is undoubtedly of remarkable interest. But there is no evi- dence that the patient studied by Dr Kumar, as Professor Dudley suggests had accelerated protein catabolism- 1. MacGregor, G. A. Br. med. J. 1971, ii, 275. 2. Karlish, A. J., MacGregor, G. A. Lancet, 1970, ii, 330. 3. Caspary, E. A., Field, E. J. Br. med. J. 1971, ii, 143. 4. Caspary, E. A., Field, E. J., MacGregor, G. A. Unpublished. 5. Kumar, R., Steen, P., McGeown, M. G. Lancet, 1972, ii, 1005. 6. Pimstone, B. L., Wittmann, W., Hansen, J. D. L., Murray, P. ibid. 1966, ii, 779. 7. Dudley, H. ibid. 1972, ii, 1255.
Transcript of VIRAL INFECTIONS AND MULTIPLE SCLEROSIS
490
meq. per litre, standard bicarbonate 13-6 meq. per litre, Paûz160 mm. Hg (breathing oxygen by face-mask). 250 meq.bicarbonate was administered, and subsequent blood-gasanalysis showed normal values, pH 7-31, PaCÛ2 42 mm. Hg,base excess -2 meq. per litre, PaÛ2 185 mm. Hg. A chestinfection developed subsequently, and the patient died onthe thirteenth postoperative day.The principle of maintaining an adequate nutritional
state in the patient undergoing major surgery has beenrepeatedly stressed. Aminoacids should be administeredto make up protein losses over the period of surgery, andcalories are also required to spare protein from catabolism.If no carbohydrate is supplied, ketone bodies are formedfrom the breakdown of fat which also results in acidosis.The profound metabolic acidosis noted in both these
patients was probably precipitated by the transfusion of alarge quantity of aminosol/fructose/ethanol. In theimmediate postoperative period reserves of alkali are
depleted, resulting in severe acid-base instability. Theresulting pathophysiological changes may well contributeto suture-line dehiscence and other complications whichprejudice survival.
St George’s Hospital,London SW1.
Royal Hampshire County Hospital,Winchester.
J. W. S. RICKETT.
D. J. BOWEN.
SERUM-THYROTROPHIN AND
HYPERCHOLESTEROLÆMIA
SIR,-Hypothyroidism is known to be a risk factor forcoronary heart-disease (C.H.D.). It has even been suggestedthat preclinical hypothyroidism is also a risk factor forC.H.D.1 Fowler et al. have indicated that hypercholestero-laemia may precede other evidence of thyroid failure.
Since the most sensitive indicator of slight thyroid hypo-function seems to be an increase in serum-thyrotrophin(T.s.H.),3 we compared the serum-T.S.H. levels of a group of50-year-old men who had hypercholesterolxmia with T.S.H.levels in a control group.The men were screened for C.H.D. risk factors in a study
of preventive medicine. A second blood-sample was takenfrom eighty of those with cholesterol values in the highestdecile. One hundred and twenty-seven men from the same
population but with cholesterol values below the highestdecile acted as controls. The serum from both groups was
separated, frozen, and stored. The blood-samples from thecontrols were taken in the same month as those from the
persons with hypercholesterolaemia.The immunoreactive T.S.H. in 01 ml. serum was assayed
by a radioimmunosorbent technique 4 using 125I-labelledhuman pituitary T.S.H. (National Pituitary Agency) andanti-T.S.H. coupled to cyanogen-bromide-activated’ Sephadex’. The standard (Medical Research CouncilH.T.S.H. research standard A) was dissolved in serum withundetectable or low levels of T.S.H. The limit of sensitivitywas 0-5 units per ml. The cholesterol and the triglycerideswere assayed in an isopropanol extract of serum by using aTechnicon dual-channel system (N-24A and N-70).The mean values for cholesterol (p < 0’001) and trigly-
ceride (p < 0-0025) were significantly higher in the hyper-choIesterolEemic group than in the control group (seeaccompanying table). There was no significant differencebetween the serum-T.s.H. levels in the two groups. Therewas no correlation between the T.s.H. values and the serum-
1. Bastenie, P. A., van Haelst, L., Bonnyns, M., Neve, P., Staquet, M.Lancet, 1971, i, 203.
2. Fowler, P. B. S., Swale, J., Andrews, H. ibid. 1970, ii, 488.3. Hershman, J. M., Pittman, J. A. New Engl. J. Med. 1971, 285, 997.4. Wide, L. Acta endocr., Copenh. 1969, suppl. 142, p. 207.
BLOOD-LIPIDS (MBAN±S.D.) AND SERUM-T.S.H. VALUES IN PERSONSWITH HYPOCHOLBSTEROLAMIA AND CONTROLS
cholesterol values (r=0-ll, P> 0-05). The low T.S.H. valuesin our study suggest that the frequency of mild hypo-thyroidism in patients with hypercholesterolaemia is verylow.
Departments of Internal Medicineand Clinical Chemistry,University Hospital,Uppsala, Sweden.
H. HEDSTRANDL. WIDE.
VIRAL INFECTIONS ANDMULTIPLE SCLEROSIS
SIR,-Professor Field proposes that in multiple sclerosis(M.s.) persisting viruses may act as adjuvants in an auto-immune attack on myelin. But he and Mr Caspary mayhave already supplied a more old-fashioned answer to theproblem. Measles, for instance, is an acute illness-
particularly in the rare form called " black measles".Serum-antibody levels to measles virus are high in auto-immune diseases, chronic active hepatitis, and M.s., but itis still uncertain whether this results from an atypicalimmune response or to latent measles infection. If theinfection occasionally. behaves as a " slow virus ", an
additional adjuvant is probably needed to allow it accessinto the brain. Freund’s complete adjuvant has experi-mentally this effect. Dead mycobacteria 1 may then makethe difference between mumps encephalitis, for example,and less dangerous mumps meningitis. An earlier andsustained immune alteration may have initially triggeredthe sensitised lymphocytes in M.s. In Britain, tuberculosisand more often sarcoidosis are now possibly the culprits.Raised immunity is a feature of sarcoidosis,2 and Casparyand Field 3 showed how wide and prolonged the cell-mediated immunity is in this disease. They also foundthat only one of our dozen cases of suspected late-stagesarcoidosis 4 failed to show by lymphocyte-sensitisationtests the immunopathology of sarcoidosis. This patienthas had myasthenia gravis for 28 years, and her memory-lymphocytes for the event have now probably died. Silent
progression of "healed" sarcoidosis may account for
many ills: perhaps it may sometimes take a part in thepathogenesis of M.s.Wood Cottage,Chilworth,Surrey. GERALD A. MACGREGOR.
RENAL FAILURE OR SIMPLE STARVATION ?
SiR,-Dr Kumar and his colleagues 5 report a case ofmalnutrition as a cause of chronic renal failure. Thisassociation, already suggested by Pimstone et aI.,6 is
undoubtedly of remarkable interest. But there is no evi-dence that the patient studied by Dr Kumar, as ProfessorDudley suggests had accelerated protein catabolism-
1. MacGregor, G. A. Br. med. J. 1971, ii, 275.2. Karlish, A. J., MacGregor, G. A. Lancet, 1970, ii, 330.3. Caspary, E. A., Field, E. J. Br. med. J. 1971, ii, 143.4. Caspary, E. A., Field, E. J., MacGregor, G. A. Unpublished.5. Kumar, R., Steen, P., McGeown, M. G. Lancet, 1972, ii, 1005.6. Pimstone, B. L., Wittmann, W., Hansen, J. D. L., Murray, P. ibid.
1966, ii, 779.7. Dudley, H. ibid. 1972, ii, 1255.
