768

In a free market those whose services were not wanted would close. Can that be even contemplated for a large hospital? Already hospitals are thinking that they might not for ever have to provide all the obvious specialties, but what is a also

general.

general hospital without, say, paediatrics or with expert advice remotely placed in some laboratory combine? What will really happen when a budgetholding practice runs out of money? More important, since there have been some ominous signs of GPs sanitising their lists to remove potential high consumers of care, what will happen when patients move? Budgets may not be rigidly fixed at so much per patient but the figure will not easily be adjusted year on year to take account of a chronically sick family moving from one part of the country to another. Will budget holders have such leverage over their peers that they can demand priority for hospital appointments and admissions? In all the talk of budgets and trusts, community medical services have been neglected. So have research and teachingessential functions that until recent years were happily and pragmatically accommodated within the NHS. What about salaries? Will not local negotiations mean that successful units will prosper even more and afford more, and the reverse? And who is going to monitor the success or failure of these experiments, and how? After all, we seem to be heading towards four sorts of health service, not one-internal markets everywhere but with no budget holders or trusts for miles or with one or the other or sometimes both. A recipe for chaos. The Health Departments are already talking of an era when few hospitals are not trusts.9 Education is the latest arm of Britain’s Welfare State in which inducements are being offered to those seeking self governing status, but in the NHS the slush fund for bribes and coercions ought to be exhausted by now. The NHS reforms ran up a bill of 390 million, including controversial "sweeteners" for the first trusts, before anything really happened.10 Let us pause and see how the few pioneers get on. Those remaining sceptical will be on the lookout for a sign so far unknown in the NHS-the patient with a thick file of notes carrying the dismal codicil, "overdrawn". 1. Editorial. Curtains up on the NHS review. Lancet 1989; i: 247-49. 2. Anon. Working papers on the NHS review. Lancet 1989; i: 454. 3. A booklet by C. Ham, R. Robinson, and M. Benzeval (Health Check. London: King’s Fund Institute. 1990. Pp 112. ISBN 1 870607 18 X. £9.95) and a paper by P. Day and R. Klein entitled Britain’s Health Care Experiment (Health Affairs in press) provide useful background for the non-UK reader. 4. Smith R. William Waldegrave: thinking. Br Med J 1991; 302: 636-40. 5. Scheffler R. Adverse selection: the Achilles heel of the NHS reforms. Lancet 1989; i: 950-52. 6. Organisation for Economic Cooperation and Development. Health care systems in transition. Paris: OECD, 1990. 7. Anon. NHS trusts. CCSC Newsl S3 1990-91: 2-3. 8. Dean M. The new NHS supermarket. Lancet 1989; 337: 721. 9. Anon. Working for patients: NHS trusts, a working guide. CCSC Newsl S1 1990-91. 10. Glasman D. Row over government’s "sweeteners" to new trusts. Health Serv J 1991, March 21: 5.

Primary hyperparathyroidism 1,25-dihydroxyvitamin D

and

Primary hyperparathyroidism has been recognised more frequently since the inclusion of calcium measurements in routine biochemical testing. The far

varied manifestations of this condition include renal stones or nephrocalcinosis, non-specific gastrointestinal symptoms, proximal muscle weakness, and occasionally psychiatric complaints. Elderly patients may present with acute hypercalcaemic crisis characterised by confusion and dehydration. Bone disease is seen in less than 10% of cases. Hypercalcaemia is not invariably present and serum phosphate concentration is often low or low normal. Serum alkaline phosphatase activity is usually normal. Inappropriately raised concentrations of parathyroid hormone confirm the diagnosis. Symptomatic primary hyperparathyroidism is treated by surgery, since in 80% of patients there is a single adenoma. Conservative management can be entertained in those who do not have overt

complications.1 Target organs for parathyroid hormone are bone and kidney. The hormone increases bone resorption; in the kidney it alters the handling of calcium and phosphate ions, and enhances the activity of lahydroxylase, leading to increased formation of 1,25dihydroxyvitamin D from 25-hydroxyvitamin D. Extracellular calcium ion concentration, among other factors, also influences renal 1,25(OH)P production.2 1,25(OH)2D can reduce parathyroid hormone synthesis; it inhibits expression of the parathyroid hormone gene by a direct and calciumindependent effect. 3,4 In patients with primary hyperparathyroidism,

1,25(OH)2D concentrations may be increased, normal, or even decreased.5,6 Shaker and colleagues’ serum

described a patient with very high concentrations of intact parathyroid hormone, severe hypercalcaemia, and low circulating concentrations of 1,25(OH)D. Her daily calcium intake exceeded 2 g. Serum calcium returned to normal with calcium restriction alone, and there was a concomitant pronounced rise in serum 1,25(OH)2D and a dramatic fall in circulating parathyroid hormone. In this patient the parathyroid glands were apparently insensitive to the increased serum calcium

lately

but

suppressive effects of 1,25(OH)2D. the inhibitory effect of Presumably, hypercalcaemia on renal 1 a-hydroxylase activity was relieved by dietary calcium restriction, the stimulatory effect of parathyroid hormone on renal lahydroxylase activity was restored. Restoration to not to

the

once

normal of serum 1,25(OH)ZD concentrations led to a fall in parathyroid hormone secretion. These observations illustrate a possible role for 1,25(OH)2D in the treatment of primary hyperparathyroidism; 1,25(OH)2D has already been used in the conservative

769

management of this condition.8 Evaluation of

analogues, including those with synthetic serum calcium than the native less activity on hormone, may be worth considering. Serum 1,25(OH)2D measurements might be of limited use in the differential diagnosis of severe hypercalcaemia9 but could help to identify patients responsive to treatment with these metabolites. Increasing public awareness of osteoporosis might encourage more postmenopausal women to take oral calcium supplements. Since people in this age group seem to have a higher frequency of primary hyperparathyroidism,1O more cases of excessive vitamin D

calcium

supplementation leading

to

hypercalcaemia

may be anticipated. Moreover, oestrogen treatment may alter the sensitivity of the parathyroid glands to calcium," although the effect of hormone replacement therapy on the incidence of diagnosed primary hyperparathyroidism remains to be established. 1. National Institutes of Health Consensus development conference statement. Diagnosis and management of asymptomatic primary hyperparathyroidism. Bethesda: NIH, 1990. 2. Trechsel U, Eisman JA, Fischer JA, Bonjour J-P, Fleisch H. Calcium dependent, parathyroid hormone-independent regulation of 1,25hydroxyvitamin D. Am J Physiol 1980; 239: E119-24. 3. Russell J, Letterri D, Sherwood LM. Suppression by 1,25hydroxyvitamin D3 of the pre-proparathyroid hormone gene.

Endocrinology 1986; 86: 2864-66. J, Naveh-Many T, Mayer H, Schmelzer HJ, Popovtzer MM. Regulation by vitamin D metabolites of parathyroid hormone gene transcription in vivo in the rat. J Clin Invest 1986; 78: 1296-301. 5. Lalor BC, Mawer EB, Davies M, Lumb GA, Hunt L, Adams PH.

4. Silver

Determinants of serum concentration of 1,25-dihydroxyvitamin D in primary hyperparathyroidism. Clin Sci 1989; 76: 81-86. 6. Thakker RN, Fraher LJ, Adami S, Karmali R, O’Riordan JLH. Circulating concentrations of 1,25-dihydroxyvitamin D3 in patients with primary hyperparathyroidism. Bone Mineral 1986; 1: 137-44. 7. Shaker JL, Krawczyc KW, Findling JW. Primary hyperparathyroidism and severe hypercalcaemia with low circulating 1,25-dihydroxyvitamin D. J Clin Endocrinol Metab 1990; 71: 1305-09. 8. Patron P, Gardin JR, Borrensztein P, Prigent A, Paillard M. Marked direct suppression of primary hyperparathyroidism with osteitis fibrosa cystica by intravenous administration of 1,25dihydroxycholecalciferol. Mineral Electrolyte Metab 1989; 15: 321-25. 9. Wortsman J, Haddad JG, Posillico JT, Brown EM. Primary hyperparathyroidism with low serum 1,25-dihydroxyvitamin D levels. J Clin Endocrinol Metab 1986; 62: 1305-08. 10. Mundy GR, Cove DH, Fisken R. Primary hyperparathyroidism: changes in the pattern of clinical presentation. Lancet 1980; i: 1317-20. 11. Boucher A, D’Amour P, Hamel L, et al. Estrogen replacement decreases the set point of parathyroid hormone stimulation by calcium in normal postmenopausal women. J Clin Endocrinol Metab 1989; 68: 831-36.

Chondroprotection Osteoarthritis is now widely believed to be not merely a wear and tear state that inexorably leads to joint failure but a potentially reversible joint remodelling process initiated by various insultS.1-3 In-vitro studies show that non-steroidal antiinflammatory drugs (NSAIDs) can promote or inhibit cartilage breakdown by altering cytokine-

induced

cartilage resorption,44 by modifying proteoglycan and collagen synthesis5 and degradation, 6,7 and by suppressing or boosting release of neutral proteases.7 Thus it is tempting to recommend NSAIDs that

deemed to be "chondroprotective" because of their ability in vitro to inhibit cartilage catabolism. However, as Dochertyl has pointed out, chondroprotection is a complex issue. Animal and human cartilage may behave differently; studies of are

chondroprotection by individual NSAIDs have yielded inconsistent results;7 and there may be considerable variation within individual studies.8 Measurements of tissue and synovial fluid concentrations of NSAIDs and of their metabolites have proved difficult to reproduce experimentally.7,9 Moreover, it is by no means certain that osteoarthritis is a disorder that is confined to cartilage. To concentrate on measurement of cartilage metabolism is to ignore what may be clinically important modifying effects of NSAIDs on bone, joint capsule, ligaments, and muscles.1 There have been no clinical studies showing that NSAIDs have a beneficial modifying effect in human osteoarthritis,1,2 and how such benefit should be measured remains unclear. Similar difficulties have been encountered in the assessment of second-line or disease-modifying drugs in rheumatoid arthritis.10.1z In both conditions

radiographic changes are an inadequate outcome criterion; they are difficult to measure13 and may have limited clinical relevance, as shown by discordance between radiographic changes, pain, and function in osteoarthritis of the hand.14,15 The difficulties of outcome assessment in osteoarthritis have been highlighted by reports that some NSAIDs (notably indomethacin) can exacerbate osteoarthritis of the hip.16-18 The evidence for this NSAID arthropathy is not entirely convincing; questions have been raised1 about study design (including case numbers, lack of control for confounding variables, and measurement of radiographic progression). A similar arthropathy has been described in non-NSAID users.19

Against this background of uncertainty, manufacturers of some NSAIDs continue to issue datasheets that cautiously highlight research into the possible chondroprotective effects of their drugs. For example, the October 1990 datasheet for ’Surgam’ (tiaprofenic acid) states that in-vitro experiments with this agent "suggest a neutral or possibly beneficial effect of tiaprofenic acid on joint cartilage under experimental conditions. The clinical significance of these findings is not known but is being further investigated". The wording is reasonable yet nevertheless seems designed to raise the possibility that this drug might be more than just another NSAID. Are patients and prescribers misled by such statements? Equally, is such speculation helpful? The wording of the Surgam datasheet may satisfy the few prescribers who are familiar with research into the effects of NSAIDs on cartilage. However, among the great majority of busy clinicians who attempt to comb through the largely amorphous mass of available NSAIDs,2° some might be tempted to favour such

Primary hyperparathyroidism and 1,25-dihydroxyvitamin D.

768 In a free market those whose services were not wanted would close. Can that be even contemplated for a large hospital? Already hospitals are thin...
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