844

will be required, giving the opportunity to staple or exciseany cysts or bullae, and is almost 100% effective.

In the management of a first episode of spontaneouspneumothorax the initial options are observation alone,simple aspiration, or tube drainage with pleurodesis. Muchwill depend on the size of the pneumothorax and on riskfactors such as distance from hospital or future air travel, aswell as any underlying lung disease. The presence ofestablished airway disease with lung overinflation wouldsuggest a more active approach, since the consequences of arecurrent pneumothorax may be more serious in such

patients. Conversely, a pneumothorax in association withcystic fibrosis, or in a young patient with advanced lungdisease, should now be treated less aggressively, since aprevious pleurodesis increases the difficulty and risks of anyfuture lung transplantation. Whilst the Danish study doesnot help us to decide whether to try simple aspiration or toopt for tube drainage, it encourages the frequent use of talcpleurodesis with pleural intubation.

STONES AND KILOGRAMS

THE major predictors of cholesterol gallstone disease areadvancing age and female sex. Race is also important: NorthAmerican Indians who have cholelithiasis than do

Caucasians, who themselves have more than blacks orJapanese. These important associations offer no scope forpreventive medicine. But what about the potential role ofdiet, drugs, and pregnancy in gallstone formation? Couldstones be avoided by manipulation of risk factors?The most potent known inducer of human gallstones is

clofibrate, which increases biliary cholesterol excretion. IBecause other fibric acid hypolipidaemic drugs have asimilar mechanism of action, they must be under suspiciontoo. This side-effect alone is a convincing argument forrestricting the use of clofibrate to small groups of patients-eg, those with pronounced hypertriglyceridaemia or

intermediate-density hyperlipoproteinaemia (Fredricksontype 3). By contrast, the potent inhibitors of cholesterolsynthesis such as simvastatin and lovastatin will probablyprotect against gallstones.2 Octreotide (the somatostatinanalogue) profoundly reduces gallbladder motility and latelyhas been associated with gallstone formation.3 No otherdrug group has been conclusively shown to have the samepotential for stone induction as do the fibrates; in particular,the doses of oestrogens used for contraception or for

hormone replacement therapy appear to be safe. However,pregnancy does increase the risk of gallstones.4-6 Thelikelihood of stones developing probably increases seriallywith each child, and the risk becomes appreciable after thesecond pregnancy. Whether this observation will alter

family planning practices seems doubtful.

1. Bateson MC, MacLean D, Ross PE, Bouchier IAD. Clofibrate therapy and gallstoneinduction. Am J Dig Dis 1978; 23: 623-28.

2. Duane WC, Hunninghake DB, Freeman ML, Pooler PA, Schlasner LA, GebhardRL. Simvastatin, a competitive inhibitor of HMG Co A reductase, lowerscholesterol saturation of gallbladder bile. Hepatology 1988, 8: 1147-50.

3. McKnight JA, McCance DR, Crothers JG, Atkinson AB. Changes in glucosetolerance and development of gallstones during high dose treatment with octreotidefor acromegaly. Br Med J 1989, 299: 604-05.

4 Khuroo MS, Mahajan R, Zargar SA, Javid G, Sarru S. Prevalence of biliary tractdisease in India: a sonographic study in adult population in Kashmir. Gut 1989; 31:201-05.

5. Barbara L, Sama C, Labate AMM, et al. A population study on the prevalence ofgallstone disease, the Simione study. Hepatology 1987; 7: 913-17

6. GREPCO. Prevalence of gallstone disease in an Italian adult female population. Am JEpidemiol 1984; 119: 796-805.

Diet has received much attention as a potential cause orcure of gallstone disease. The low prevalence of gallstones inunderdeveloped African populations has been attributed totheir high vegetable intake, and vegetarian women areprotected from gallstones.7 It is unclear whether meat causescholelithiasis since there are obviously other lifestyle factorsthat may be crucial in these groups. Alcohol in moderateamounts seems to prevent gallstones, although in excess willpredispose to them if cirrhosis develops. No firmconclusions can be drawn about dietary cholesterol, fat,protein, carbohydrate, fibre, minerals, or vitamins.8

It is uncontentious old news that obesity causes

gallstones.9-14 (Hypertriglyceridaemia has also been linkedwith gallstones,15 although this is not a universal finding.1)The mechanism of stone formation in obese people is

probably a combination of excess cholesterol saturation ofbile16,17 and reduced gallbladder motor function.18 Thefatter the subject the higher the chances of gallstones-andthis is one reason given for advising obese patients to loseweight. However, the process of weight reduction by diet orbariatric surgery can lead to development of gallstones in itsown right.19-22 Various measures may be tried to preventstone formation in patients on a reducing diet-eg, coursesof agents such as chenodeoxycholic acid, ursodeoxycholicacid, terpenes, or aspirin.23-26 Ursodeoxycholic acid is

probably the best documented, but cannot yet berecommended for all dieters. If being fat and getting slim areboth risky the only sensible advice is not to put on excessweight in the first place. Is it a coincidence that three of themost eminent physicians in Britain with an interest ingallstone disease are of impressively slender build?

7. Pixley F, Mann J. Dietary factors in the aetiology of gallstones: a case control study.Gut 1988; 29: 1511-15.

8. Bateson MC, ed. Gallstone disease and its management. Lancaster. MTP, 1986.9. Horn G. Observations on the aetiology of cholelithiasis. Br Med J 1956; iii: 732-37.

10. Zahor Z, Stemby NH, Kagan A, Uemura K, Vanecek R, Vichert AM. Frequency ofcholelithiasis in Prague and Malmo. An autopsy study. Scand J Gastroenterol 1974;9: 3-7.

11. Rimm AA, Wemer LA, van Yserloo B, Berstein RA. Relationship of obesity anddisease in 73 532 weight conscious women. Publ Health Rep 1975; 90: 44-51.

12. Haffner SM, Diehl AK, Stem MP, Hazuda HP. Central adiposity and gallbladderdisease in Mexican Americans. Am J Epidemiol 1989; 129: 587-95.

13. Jorgensen T. Gallstones in a Danish population. Gut 1989; 30: 528-34.14. Maclure KM, Hayes KC, Colditz GA, Stampfer MJ, Speizer FE, Willett WC

Weight, diet and the risk of symptomatic gallstones in middle-aged women N EnglJ Med 1989; 321: 563-69.

15. van der Linden W, Bergman F. An analysis of data on human hepatic bile.Relationship between main bile components, serum cholesterol and serum

triglycerides. Scand J Lab Invest 1977; 37: 741-47.16. Freeman JB, Meyer PD, Printen KJ, Mason EE, DenBesten L. Analysis of

gallbladder bile in morbid obesity. Am J Surg 1975; 129: 163-66.17. Mabee TM, Meyer P, DenBesten L, Mason EE. The mechanism of increased

gallstone formation in obese human subjects. Surgery 1976; 79: 460-68.18. Kucio C, Besser P, Jonderko K. Gallbladder motor function in obese versus lean

females. Eur J Clin Nutr 1988; 42: 121-24.19. Liddle RA, Goldstein RB, Saxton J. Gallstone formation during weight reduction

dieting. Arch Intern Med 1989; 149: 1750-53.20. Amaral JF, Thompson WR. Gallbladder disease in the morbidly obese. Am J Surg

1985; 149: 551-57.21. Wattchow DA, Hall JC, Whiting MJ, Bradley B, Iannos J, Watts JM. Prevalence and

treatment of gallstones after gastric bypass surgery for morbid obesity Br Med J1983; 286: 763-64.

22. Mok HYI, von Bergmann K, Crouse JR, Grundy SM. Biliary lipid metabolism in obesity. Effects of bile acid before and after weight reduction. Gastroenterology1979; 76: 556-67.

23. Broomfield PH, Chopra R, Sheinbaum RC, et al. Effects of ursodeoxycholic acid andaspirin on the formation of lithogenic bile and gallstones during loss of weightN Engl J Med 1988; 319: 1567-72.

24. Jungst D, Brenner G, Pratschke E, Paumgartner G. Low dose ursodeoxycholic acidprolongs cholesterol nucleation time in gallbladder bile of patients with cholesterolgallstones. J Hepatol 1989; 8: 1-6.

25. von Bergmann K, Beck A, Engel C, Leiss O. Administration of a terpene mixtureinhibits cholesterol nucleation in bile from patients with cholesterol stones. KlinWochenschr 1987; 65: 458-62

26 Hood K, Gleeson D, Ruppin DC, Dowling RH, and the British/Belgian GallstoneStudy Group. Prevention of gallstone recurrence by non-steroidal anti-

inflammatory drugs. Lancet 1988; ii: 1223-25.