910

temperatures,18 19 or storage in tissue-culture’a-’6are possibilities. So far, functional preservation ofhuman islets has been reported only after tissue-culture.15 16 These systems have the advantage thatislet function can be tested before transplantation;and, in addition, there is still the possibility thatorgan culture may reduce the immunogenicity ofthe transplanted tissue.20-22

Before attempts to transplant islets into diabeticpatients, further experimental work must be doneon animals. We need to be more sure that correc-tion of carbohydrate metabolism in the recipientwill prevent the secondary complications of dia-betes. Furthermore, the yield of human pancreatic-islet isolation will have to be increased, and thismay require completely new techniques. Probablythis part of the project will be the most difficult.Thereafter, there seems no reason to suppose thatrejection and immunosuppressive therapy will beharder to manage with transplanted islet cells thanwith other transplanted tissues. But a note ofcaution is due. The process responsible forislet-cell deterioration in diabetes, possibly an

autoimmune reaction,23 may also affect newlytransplanted islets. In other words, a technicallyadequate islet transplant might not benefit the dia-betic recipient.

Lactase DeficiencyTHE disaccharide lactose is found naturally only

in mammalian milk. In young mammals lactase isfound in the brush border of the enterocyte; this

enzyme releases the monosaccharides glucose andgalactose which are then actively transported intothe epithelial cell. Trace amounts of lactose maypass the mucosal barrier but there is no hydrolysiselsewhere in the body and the sugar is lost in theurine. A few mammals, such as the Californian sea-lion, have no lactase at birth; their mother’s milkcontains no lactose.24 Human infants, with the rareexception of those with primary alactasia, havehigh lactase levels at birth. Concentrations fall

quite rapidly in the first 4 or 5 years and in manypopulations reach very low levels by adolescence.

In three major ethnic groups lactase usually per-sists into adult life. The Northern Europeans andtheir descendants all over the world form the mostfamiliar group. In Africa several Hamitic tribes in

Uganda, Kenya, and Ruanda show persistence,,25 asdo the Hausa and Fulani in Nigeria;26these people

18. Knight, M. J., Scharp, D. W., Kemp, C. B., Ballinger, W. F., Lacy, P. E.Cryobiology, 1973, 10, 89.

19. Frankel, B. J., Gylfe, E., Hellman, B., Idahl, L.-A, J. clin. Invest. (in thepress).

20. Raaf, J. H., Farr, H. W., Meyers, W. P. L., Good, R. A. Am. J. Surg. 1974,128, 478.

21. Lafferty, K. J., Cooley, M. A., Woolnough, J., Walker, K. Z. Science, 1975,188, 259.

22. Boyles, R. R., Seltzer, H. S. Diabetes, 1975, 24, suppl. 2, p. 420.23. MacCuish. A. C., Irvine, W. J. Clins, Endocr. Metab. 1975, 4, 435.24. Sunshine, P., Kretchmer, N. Science, 1964, 144, 850.25. Cook, G. C., Kajubi, S. K. Lancet, 1966, i, 725.

are unrelated to the Bantu. In the Middle East theBedouin, Saudi, and Yemeni Arabs show enzymepersistence while Eastern Mediterranean people donot 27 Milk and lactose feeding in man does not in-crease enzyme levels and there is now good evi-dence that a recessive autosomal gene determinespersistence?* The adaptive changes in milk-fed ratsare small compared with the tenfold difference inhuman adults with and without deficiency. The ageat which deficiency becomes evident shows geo-graphical differences-between 1 and 4 years inThailand and between 5 and 20 years in Finland.Both genetic and environmental factors may be re-sponsible. When the enterocyte is damaged lactaselevels are depressed more than other disaccharidesand low levels may continue for several monthsafter the primary disease is relieved. Conditions

causing low levels include acute gastroenteritis,protein-energy malnutrition, tropical sprue, coeliacdisease, cystic fibrosis, ulcerative colitis, and

gastrointestinal surgery in infants.Several hypotheses have been proposed to

explain enzyme persistence in certain populations.In animals, dietary lactose enhances the absorptionof calcium as effectively as vitamin D, and FLATZand ROTTHAUWE29 have proposed that milk-drink-ing would have an antirachitic effect in populationsexposed to little sunlight. Thus lactose persistence,like a depigmented skin, would have survival valuein Northern Europe; this hypothesis does not

account for the other ethnic groups. The milking ofdomestic sheep and goats began between five thou-sand and eight thousand years ago in South-WestAsia, where cattle and camels were used not longafter. Man may be presumed to have been orig-inally lactase deficient, but mutants with the

enzyme would be able to adopt the milk-drinkinghabit more easily and so gain in biological fitness.It has been calculated that in 400 generations abiological fitness 1% greater than average woulddecrease the prevalence of deficiency from 90% to16%.30 All the present populations with enzyme per-sistence seem to have originated in South-WestAsia; the African groups are all cattle pastoralistsand the Arabian groups still use camel milk. COOK"has suggested that since water absorption is cou-

pled to that of monosaccharides, so adults with

high lactase levels could better withstand epidemicsof cholera. Low enzyme levels have been overcome

by several cultural adaptations. Thus, bacterial fer-mentation destroys the lactose in cheese, ghee, andyoghurt; while the addition of lime-juice in Mexico,or baobab juice in Africa, precipitates the proteincurd.

26. Kretchmer, N., Ransome-Kuti, O., Hurwitz, R., Dungy, C., Alakija, W ibid1971, ii 392.

27. Cook, G. C., Al-Torki, M. T. Br. med. J. 1975, iii. 135.28. Sahi, T., Isokoski, M., Jussila, J., Launiala, K., Pyöväla, K. Lancet, 1973.

ii, 823.29. Flatz, G., Rotthauwe, H. W. ibid p.76.30. Bayless, T. M. Gastroenterology, 1972, 63, 524.

911

Lactase-deficient subjects are normally definedas those having a blood-glucose rise of less than 20mg/dl after 50 g/m oral lactose dose; a tolerancetest with 25 g glucose and 25 g galactose should benormal. Large lactose doses should be given withcaution, since the resulting abdominal bloating,flatulence, colic, and diarrhoea may be prodigious.Symptoms result from an increased osmotic load inthe small bowel, accentuated by bacterial fermen-tation of lactose in the colon. If no symptoms occurwith a large dose, then enzyme deficiency is unlike-ly; as a screening test patients may be given 50 glactose and 50 g glucose on different days and thesubjective effects compared.Within a population deficient individuals may

adapt their milk intake to their tolerance level.Thus PAIGE et al. 31 showed in the U.S.A. that 20%of 300 Black schoolchildren drank less than halftheir 240 ml milk portion compared with 10% of150 White children; proven malabsorption wastwice as common among the non-drinkers. In Okla-homa, 63 of 100 deficient subjects were aware thatthey were milk intolerant 32 BAYLESS et al. 33 havelately studied 166 hospital patients in Maryland:31% of the deficient subjects left three-quarters oftheir milk portion compared with 13% of "normal"subjects; 72% of the deficient group were aware oftheir intolerance to one glass of milk. When 12 gof lactose, equivalent to 240 ml of milk, was givento 44 deficient subjects, 30 had symptoms. Morethan two-thirds of a deficient group of Africans had

symptoms after milk or lactose; 34 however, sometolerance developed after ten days, althoughjejunal lactase levels did not rise. Intraluminal fluidmovement, 35 lactose-barium examinations,36 andbreath-hydrogen excretion 37 are frequently abnor-mal when 5 to 12 g of lactose is given to deficientsubjects, even when no symptoms occur; the rise inblood-sugar after 240 ml of raw milk is reduced.Thus it is well established that a considerable

proportion of deficient subjects develop symptomsand physiological changes after drinking normalamounts of milk. To the physician practising intemperate countries the main relevance of lactasedeficiency is that it may masquerade as irritable-bowel syndrome and should be suspected particu-larly in non-European patients. In a recent per-sonal paper a Sudanese doctor vividly described hisown symptoms;38 this case-history underlines howeasily the condition may be overlooked. When pep-tic-ulcer patients, and others, are being advised

31. Paige, D. M., Bayless, T. M., Ferry, G. D., et al. Johns Hopk. med. J. 1971,129, 163.

32 Welsh, J. D. Medicine, 1970, 49, 257.33 Bayless, T. M., Rothfeld, B., Massa, C., Wise, L., Paige, D. M., Bedine, M.

S. New Engl. J. Med. 1975, 292, 1156.34. Cook, G. C. in Intestinal Enzyme Deficiencies and their Nutritional Implica-

tions (edited by B. Borgstrom, A. Dahlquist, and L. Humbraeus). Upp-sala, 1973.

35 Bedine, M. S., Bayless, T. M. Gastroenterology, 1973, 65, 735.36 Laws, J. W., Neale, G. Lancet, 1966, ii, 139.37. Levitt, M. D., Donaldson, R. M. J. Lab. clin. Med. 1970, 75, 937.38. Ahmed, H. F. Lancet, 1975, ii, 319.

about dietary milk, thought must always be givento the possibility of lactase deficiency. Not onlymay symptoms be made worse but also the patientmay be nutritionally worse off. Conditions causingsecondary enzyme deficiency should be looked at inthe same way. A reported association between lac-tase deficiency and osteoporosis 39 has been

explained in terms of prolonged avoidance of milk.In developing countries the implications are

greater. Malnourished children usually havesecondary deficiency and in their nutritional reha-bilitation this must be borne in mind, especiallywhen diarrhoea is already a symptom. The nutri-tional benefit of milk has to be weighed against thepossible deleterious effect upon fluid balance. De-cisions must be based upon local experience. Manycentres now use a mixture of sucrose, a vegetableoil, and milk powder, thus providing an energy-dense food with a lower concentration of lactose.Similar mixtures have been successful for faminerelief in Biafra and Ethiopia.40 Further investiga-tions are necessary before definite statements canbe made about protein and calcium absorptionfrom milk in deficient subjects. Another problem inthe tropics is the adoption, by the new urban elite,of Western milk-drinking habits; symptoms inadults and schoolchildren are common and mayeasily be misinterpreted.

VIBRATION-INDUCED WHITE FINGER

IN their report this year on the vibration syndrome 41the Industrial Injuries Advisory Council advised againstinclusion of vibration-induced white finger as a prescrib-ed disease, thus supporting the conclusion of the 1954report on Raynaud’s phenomenon 42 In both reportsthere were minority views maintaining that there is ahard core of cases in which vibration-induced white

finger results in social handicap, increase in’sicknessabsence, and, in severe cases, change of employment.Both reports draw attention to (a) the difficulty of estab-lishing that a case is occupational in origin, (b) the prob-lems of diagnosis and assessment, and (c) the trivialityof the condition. To assist in their investigations tworesearch projects were set up. The first, by Stewart andGoda; covered over a thousand vibratory-tool users ofwhom 542 had v.w.F. They judged that the conditionwas not disabling, except that hobbies sometimes had tobe forgone in cold weather because exposure of thehands to low temperature was a stimulus for white

finger. They described the development of callus in thefingers and thumbs in response to the work, and

regarded this as evidence supporting earlier findings

39. Birge, S. J., Keutmann, H. T., Cuatrecasas, P., Whedon, G. D. New Engl.J. Med. 1967, 276, 445.

40. Mason, J. B., Hay, R., Levesche, J., Peel, S., Darley, S. Lancet, 1974, ii,332.

41. Industrial Injuries Advisory Council. Report on the Vibration Syndrome.National Insurance (Industrial Injuries) Act, 1946. Cmnd. 9347. H.M.Stationery Office, 1975.

42. Industrial Injuries Advisory Council. Report on Raynaud’s Phenomenon.National Insurance (Industrial Injuries) Act, 1946. Comnd. 9347. H.M.Stationery Office, 1954.

43. Stewart, A. M., Goda, D. F. Br. J. ind. Med. 1970, 27, 19.