489

abnormal in FHH. The renal tubular reabsorption of filteredcalcium is greater than expected for the parathyroid hormoneconcentration and in 3 patients the increased reabsorption hasbeen shown to persist after total parathyroidectomy. IS Thereis also an increased tubular reabsorption of magnesium,about half the affected subjects having hypermagnesaemia: 11 ithe renal tubular handling of magnesium is normal in bothhyperparathyroidism and hypoparathyroidism.16 The renaltubular maximum reabsorption rate for phosphate related toglomerular filtration rate (TmP/GFR) is normal or onlyslightly lowered.4,5 The renal excretion of calcium is low inrelation to dietary intake.’,2 Circulating parathyroidhormone concentration is usually normal or raised, andpreliminary data suggest that the serum concentration of1,25-dihydroxycholecalciferol is normal,4 so there is

probably also an abnormality in the mechanism for theabsorption of calcium from the gastrointestinal tract. Theseclinical and biochemical observations are difficult to explainin terms of existing knowledge of the pathophysiology ofcalcium homoeostasis, and seem irreconcilable at presentwith the one-gene/one-enzyme (or one-cistron/one-

polypeptide) concept.In an individual hypercalcaemic patient, the differentiation

of FHH from sporadic or familial hyperparathyroidism andfrom the other causes of hypercalcaemia is helped by theabsence of specific symptoms and of a family history ofsymptoms, and by the lack of radiological changes in FHH.The measurement of plasma parathyroid hormone and theurinary excretion of cyclic AMP do not separate FHH fromhyperparathyroidism (or, with some parathyroid hormoneassays, from malignant diseasel’). A pointer to the diagnosisof FHH, in the absence of renal failure, may be

hypermagnesaemia; plasma magnesium is not raised in

hyperparathyroidism.1’," A raised plasma concentration of1,25-dihydroxycholecalciferol is common in hyper-parathyroidism but not in FHH or malignant disease. 4,17,20The tubular handling of phosphate is often normal- in FHH,with a TmP/GFR greater than 0-7 mmol/1 (2-2 2 mg/dl) inadults,4 while it is usually lower in hyperparathyroidism andmay be normal or low in cancer-associated hypercalcaemia. 17Urinary calcium excretion is low in relation to the

hypercalcaemia and to the calcium intake in FHH-less thanabout 5 mmol (200 mg) a day on a free diet2,4,5-in contrast tothe increase in daily calcium excretion usually found in otherforms of hypercalcaemia in the absence of renal failure. Thehypercalcaemia does not lead to renal failure and an

increasing plasma creatinine concentration in FHH. The bestdiscriminant is probably the urinary calcium excretion perunit volume of glomerular filtrate (CaE: the product of theconcentrations of fasting urine calcium and plasma creatininedivided by urine creatinine concentration). CaE is usually lessthan 0 - 03 mmol/1 (0-12 mg/dl) of glomerular filtrate in FHHand greater than this in other types of hypercalcaemia in the15. Attie MF, Gill JR, Stock JL, Spiegel AM, Downs RW, Levine MA, Marx SJ.

Parathyroid hormone independent abnormality of renal tubular transport ofcalcium in familial hypocalciuric hypercalcemia. Clin Res 1980; 28: 384 A (abstr).

16. Rude RK, Bethune JE, Singer FR. Renal tubular maximum for magnesium in normal,hyperparathyroid, and hypoparathyroid man. J Clin Endocrinol Metab 1980; 51:1425-31.

17. Stewart AF, Horst R, Deftos LJ, Cadman EC, Lang R, Broadus AE. Biochemicalevaluation of patients with cancer-associated hypercalcemia. N Engl J Med 1980;303: 1377-83.

18. Sutton RAL. Plasma magnesium concentration in primary hyperparathyroidism. BrAW J 1970; i: 529-33.

19. King RG, Stanbury SW. Magnesium metabolism in primary hyperparathyroidism.Clin Sci 1970; 39: 281- 303.

20 Broadus AE, Horst RL, Lang R, Littledike ET, Rasmussen H. The importance ofcirculating 1,25-dihydroxyvitamin D in the pathogenesis of hypercalciuria andrenal-stone formation in primary hyperparathyroidism. N Engl J Med 1980; 302:421-6.

absence of renal failuré5,17 Such a value, if confirmed,should be taken as an indication for screening the family.Subtotal parathyroidectomy seldom cures the

hypercalcaemia of FHH and results in hypoparathyroidismin a minority.4,2l Total parathyroidectomy may be necessaryin the rare patient with recurrent life-threatening pancreatitisor severe neonatal hyperparathyroidism, but usually notreatment is required. Familial hypocalciuric hypercalcaemianeeds to be recognised so that patients are spared unnecessaryexploration for parathyroid adenoma and needless treatmentfor hypercalcaemia.

TRACHOMA CONTROL

ALTHOUGH attempts to treat trachoma have been made forat least five millennia the disease is still with us and nowaffects some 500-700 million people, most of them in ruralcommunities of the developing world. 2 million are blind,although blindness should be avoidable. The 1980s have seentwo substantial publications on the control of trachoma. TheWorld Health Organisation has outlined basic principles for’people organising a trachoma control programme; and theRoyal Australian College of Ophthalmologists2 has reportedan enormous programme to determine the state of ocular

health, especially with respect to trachoma, in ruralAustralians and to provide immediate treatment wherenecessary. The Australian programme was especiallysuccessful in identifying the importance of trachoma as apublic health problem. A total of over 100 000 people wereseen including 62 000 Aborigines. Nearly half the Aboriginalpopulation screeried had trachoma-a higher proportion thanhas been reported for many third world countries. InNorthern Territory and Western Australia in particular thefigure was about 80%. Up to 26% of Aborigines over 60 inarid regions were blind, and the average blindness rate amongthose seen was-eight times higher in Aborigines than in non-Aborigines. This survey was not the first to report ontrachoma in Australia. In the 1940s and 1950s Father Flynn,formerly at Moorfields, and Ida Mann, formerly professor ofophthalmology at Oxford, examined more than 10 000

people apiece in Central, Northern, and Western Australia,finding trachoma in up to 90% of the Aboriginal population.These reports were received with incredulity and werefollowed by other surveys and treatment programmes, butstill there is much to be done before the Royal AustralianCollege of Ophthalmologists achieves its aim to eliminatetrachoma from Australia.Trachoma starts as a chronic inflammation of the

conjunctiva brought about by Chlamydia trachomatis andcharacterised by follicles in the early stages progressing toscarring on the inside of the eyelid-cicatricialtrachoma-which directly or indirectly leads to cornealulceration and scarring and thus blindness. Both the newpublications describe rather complex grading schemes fortrachoma scoring for follicles, papillae, trichiasis/entropion,and other features of the disease, with helpful plates in fullcolour, and both give details of the organisation of trachomacontrol programmes. Both also discuss the different phases of

21. Marx SJ. Familial hypocalciuric hypercalcemia. N Engl J Med 1980; 303: 810-11.1. Dawson CR, Jones BR, Tarizzo ML. Guide to trachoma control, Geneva; World

Health Organisation, 1981.2. The National Trachoma and Eye health Program. Royal Australian College of

Ophthalmologists, 1980.

490

chemotherapy and surgical treatment. The Australians usedco-trimoxazole (trimethoprim/sulphamethoxazole) whereasW.H.O. now favours tetracyclines. In the Australian

programme 1381 people were identified as needingsurgery-for trachoma-damaged eyelids, for pterygia, and forcataract in about equal proportions. Most of these patientswere Aborigines, and nearly a sixth of the Aborigines over 60required eye operations. The importance of follow-up is

emphasised, as is the need for environmental improvement.Both publications are essential reading for those interested intrachoma control.Duke-Elder3 3 pointed out that "Trachoma is over-

whelmingly associated with the dirt, squalor and the intimateproximity of poverty, particularly in regions where the lack ofwater makes the common washbasin a social necessity andlack of material reduces towels and handkerchiefs to a

communal rag." Blinding trachoma disappeared from mostof Europe long before the advent of effective therapy,presumably because of improving standards of hygiene. IdaMann5 believed that the economically enforced residence ofAborigines in native camps attached to stations contributedto the spread of trachoma. Their ideas of hygiene wereperfectly satisfactory while they were nomadic but not whenthey remained in one camp. Both the recent publicationsrecommend improvements in water supply, water-basedsewage systems, and rubbish disposal. This need is illustratedby the general health statistics of the residents of oneAustralian village, relatively privileged in being close to atown with a hospital. Despite this, 30% of the inhabitants hadbowel infestations, about 80% had signs of malnutrition, 21070were chemically diabetic, and 27% were hypertensive. Mostof the ill health there, the report concludes, was due to poorhygiene, poor housing, ignorance, and alcohol abuse. In IdaMann’s survey,5 there was little evidence of malnutritionexcept early scurvy in 5 Aborigine children boarding at amission and eating European food (white bread and tinnedfood). The Australian report also covers cataract and othereye diseases. After the earlier surveys Ida Mann was able to

report that cataract was not common and was mostly nuclearcataract. In the recent survey cataract ranked with trachomain importance as a cause of visual impairment and in the needfor surgery; and the most common form was white posteriorsubcapsular cataract. It seems possible that, although thechanging way of life of the Aborigines may have contributedto their trachoma, it may have had a greater effect on theirlenses. This could be related to the changes in nutrition andsanitation. Perhaps Aboriginal health was better when theywere naked and nomadic in the sunshine.

PHENOLSULPHOTRANSFERASE

THAT the animal body is capable of forming sulphateconjugates of phenolic derivates has been known for over ahundred years. Sulphoconjugation represents a possiblemetabolic route for various endogenous phenolic amines aswell as drugs such as salicylamide and methyldopa. Theenzyme, or group of enzymes, responsible for sulpho-conjugation was identified in 1957’ and named

3. Duke-Elder S. Diseases of the outer eye (System of ophthalmology VIII). London:Henry Kimpton, 1965.

4. Jones BR. The prevention of blindness from trachoma. Trans Ophthal Soc U.K. 1975;95: 16-33.

5. Mann I. Culture, race, climate and eye disease. Springfield: Charles C. Thomas; 1966.1. Robbins PW, Lipmann F. Isolation and identification of active sulphate. J Biol Chem

1957; 229: 837-51.

phenolsulphotransferase (PST; EC 2.8.2.1.). PST has neverenjoyed mainstream popularity in biological research-thereactions for the most part ranging from passing curiosity toindifference (phenolsulpho- what?)-and the main reason isthat it lacks any clear strategic physiological function. It isneither substrate specific nor tissue specific. Although it canconjugate catecholamines, the tissue distribution bears norelation to sympathetic innervation; therefore PST is

unlikely to play an important part in neurotransmission.Originally identified in the periphery, PST activity was laterfound in brain, where sulphate conjugation of monoaminesand their deaminated methylated metabolites occurs

naturally. Association with central monoamine metabolismguaranteed for PST some attention from neurochemists,albeit in the shade of monoamine oxidase (MAO) andcatechol-o-methyl-transferase (COMT). The not uncommonlogic of "if it’s in the brain and has some association withmonoamines, then it might be involved in mental illness" hasbeen applied. Further, the demonstration of PST activity inhuman platelets2 has been seen as providing the opportunityof another "window into the brain" in the living patient, andhere the analogy with MAO is plain.With the aim of consolidating a position for PST in mental

health research, a symposium on PST was held at the

December, 1980, meeting of the American College ofNeuro-psychopharmacology and a collection of symposium papershas just been published.3 Brain PST has high affinity forcentral catecholamines, but the distribution of the enzymedoes not correspond to catecholamine innervation and itsspecific activity is so low that even at low catecholamineconcentrations MAO and COMT are quantitatively muchmore important metabolic pathways. It is possible that PSTtakes part in the general elimination of catecholaminemetabolites after the primary inactivation of catecholaminesby MAO and COMAT. Sulphoconjugation of the oxidiasedmethylated metabolite of noradrenaline 3-methoxy,4-hydroxyphenylglycol (MHPG) produces a zwitterionwhich has negligible net charge at physiological pH andwhich would therefore be able to diffuse across membranesand out of brain tissue with ease. It is not clear, however,whether variation in such second-line elimination would have

any substantial effect on catecholamine transmission in thebrain. Are abnormalities of sulphoconjugation associatedwith any clinical disorders of catecholamine function, centralor peripheral? In man, most of the circulating catecholaminesin plasma exist in conjugated form and there is some evidencethat a small subgroup of patients with essential hypertensionhave deficient sulphoconjugation of adrenaline, giving a

clinical syndrome equivalent to phaeochromocytoma.Despite clear differences between platelet PST and brainPST, attempts have been made to infer central PST activityfrom platelet PST in various clinical disorders of the centralnervous system. Studies of platelet PST activity in therapy-resistant depressive illness and in untreated parkinsonismhave revealed little to implicate PST in these disorders, but itmust be recognised that any such extrapolation from plateletto brain is tenuous. The signs are that schizophrenic illnesswill be the next target for PST supporters. Unless somethingmore substantial emerges, there seems little future for this

enzyme in aetiological hypotheses of mental disorder.

2. Hart RF, Renskers KJ, Nelson EB, Roth JA. Localistion and characterisation ofphenosulphotransferase in human platelets. Life Sci 1979; 24: 125-30.

3. Phenosulfotransferase in Mental Health Research. Edited by M Sandler and E UsdinLondon: Macmillan, 1981. £22.00.