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entirely exclude the possibility that a dwarf is hiding inthe corner of the room, many western researchers maynow conclude that the existence of this dwarf

approaches asymptotically to zero.

1. Bullock ML, Culliton PD, Olander RT. Controlled trial of acupuncturefor severe recidivist alcoholism. Lancet 1989; i: 1435-39.

2. Bullock ML, Umen AJ, Culliton PD, Olander RT. Acupuncturetreatment of alcoholic recidivism: a pilot study. Alcoholism (NY) 1987;11: 292-95.

3. Sacks HS, Berrier J, Reitman D, et al. Meta-analyses of randomisedcontrolled trials. N Entl J Med 1987; 316: 450-55.

4. Ter Riet G, Kleijnen J, Knipschild P. De effectiviteit van acupunctuur:De meta analyse als review-methode. Huisarts Wet 1989; 32: 176-81.

5. Ter Riet G, Kleijnen J, Knipschild P. De effectiviteit van acupunctuur:nawoord en aanbevelingen. Huisarts Wet 1989; 32: 308-12.

6. Ter Riet G, Kleijnen J, Knipschild P. De effectiviteit van acupunctuur:oorsprong en werkingemechanismen van acupunctuur. Huisarts Wet1989; 32: 170-75.

7. Mann F, Bowsher D, Mumford J, Lipton S, Miles J. Treatment ofintractable pain by acupuncture. Lancet 1973; ii: 57-60.

GALLSTONES: EPIDEMIOLOGICAL ADVANCEVERSUS PREVENTIVE STALEMATE

The introduction of ultrasonography heralded a new era inthe study of gallstone disease. Both prevalence and incidenceof gallbladder stones are readily assessed, although accuratelocalisation of common bileduct stones remains verydifficult with simple methods. Since Italian workers havebeen pace-setters in this area, Rome was an appropriatevenue for the Second International Workshop on

Epidemiology and Prevention of Gallstone Disease, in earlyDecember.

Groups of research workers in Rome (GREPCO) andBologna (Sirmione Study) have shown that women not onlyhave more gallstones but also more often complain ofsymptoms and are more often aware of their condition thanare men. However, most stones are symptomless in bothsexes. When ultrasonography is repeated after an interval ofyears, the incidence of new stones in previously stone-freesubjects can be calculated. Although there are some points ofdisagreement between the Italian groups and a study fromCopenhagen, the incidence appears to increase with age. It isalso probably true that in younger subjects the incidence inwomen is higher than in men, this difference disappearsafter the menopause. A striking result of the Danish studywas the great difficulty in showing any difference inabdominal complaints between subjects with and withoutgallstones.! The rate of development of complications ofgallstone disease such as jaundice, acute cholecystitis, andacute pancreatitis is low (about 1 % annually) and may bejust as common in patients whose stones were not initiallyassociated with any abdominal symptoms. In Italy,however, stones in patients with abdominal symptoms weremore likely to be associated with complications; thisobservation might reflect a true national difference.

Ultrasonography has revealed that gallbladder polyps aremore common than previously thought but follow-up ofpatients indicates that the polyps are seldom clinicallyimportant. Polyps are not an indication for intervention intheir own right unless there is a change in their size or in theclinical condition of the patient on review. The greatinternational variety of gallbladder disease was wellillustrated in a survey from Fukuoka, Japan (Dr S. Kono),

where gallbladder polyps are more common thancholelithiasis-the inverse of experience in Westerncountries.

Necropsy prevalence studies provide masses of data forhistorical comparison of gallbladder disease rates. Thus inScotland gallstone disease has increased to a new plateau inthe past 20 years, having previously been stable at a lowerlevel. This change did not correlate at all with figures forcholecystectomy, which appear to have a life of their own,showing a moderate fall in the years after 1977. Obesity andhigher parity were generally confirmed as important riskfactors for gallstones, with a "dose-response" effect-thefatter and more fecund the female the greater the likelihoodof stones. Overweight seems to be a less important risk factorfor men. These factors are potentially amenable to

preventive measures, unlike the strong racial and weakfamilial associations of stones.

Serum biochemical changes have been closely scrutinisedfor links with gallstones. The consensus is that generallyraised serum triglyceride levels are positively associated withgallstones, and that serum cholesterol is either not linked oris negatively associated with the presence of gallstonedisease. The lower levels of high-density lipoproteincholesterol in gallstone patients may have a pathogeneticsignificance via cholesterol secretion in bile, although themechanism is not obvious. Dr K. W. Heaton and co-workers in Bristol reported that serum insulin is higher inpeople with gallstones, and this finding correlates with theresults of an Italian survey showing that glucose tolerance isimpaired in gallstone disease. And there seems to be a linkbetween diabetes mellitus and gallstones, despite muchprevious uncertainty. The search for a specific dietarytrigger for cholesterol gallstones has been disappointing.Pasta in Italy, legumes in Latin America, and a westerniseddiet in Japan all seem to be important. Levels of ethanolintake that most people would regard as definite alcoholism(80 g or more daily) protect from gallstones; moderatedrinkers may hope for some lesser benefit, but no

recommendations are in order for the general public.The vexed question of exogenous sex steroids was

discussed at great length. There is no cogent evidence thatmodern low-dose combinations of oestrogens and

progestagens, used for oral contraception or

postmenopausal hormone replacement therapy, are

important for gallstone formation. However, patients whohave gallstones seem to come to cholecystectomy more oftenafter hormone replacement therapy or after high-doseoestrogen therapy for prostatic carcinoma. Women withgallbladder stones who take oral contraceptives are operatedupon earlier if not more frequently. This finding stronglysuggests that the sex steroids act by afffecting gallbladdermotility; by way of confirmation, sex steroid receptors havebeen found in the gallbladder.One of the most impressive initiatives is the multicentre

Italian study on cholelithiasis (MICOL), which has enrolledmore than 33 000 subjects; this approach allows within-country geographical comparisons. Results are a little

erratic, but suggest that gallstone disease is commoner insouthern Italy than in the north. Also GREPCO indicatedthat women in rural populations have a higher prevalencethan city dwellers. Odd fluctuations have been shown inprevious studies, and attempts to establish figures for

regional variations in gallstone disease for Britain yieldedcontradictory results. 3.4 The main importance of MICOL isthat it should eventually help to pinpoint more of the factors

22

that are crucial to the formation of cholesterol stones and

explain changes in frequency.As for prevention--one can only reinforce the currently

fashionable counsel for the healthy lifestyle which attemptsto keep us slim and avoid very large families.

1. Jørgensen T. Abdominal symptoms and gallstone disease: an

epidemiological investigation. Hepatology 1989; 9: 856-60.2. Royal College of General Practitioners’ Oral Contraception Study. Oral

contraceptives and gallbladder disease. Lancet 1982; ii: 957-59.3. Watkinson G. The autopsy incidence of gallstones in England and

Scotland. Proceedings Third World Congress of Gastroenterology,Tokyo, 1967; 4: 125-30.

4. Barker DJP, Gardner MJ, Power C, Hutt MSR. Prevalence of gallstonesat necropsy in nine British towns: a collaborative study. Br MedJ 1979;ii: 1389-92.

NORMAL-PRESSURE HYDROCEPHALUS

There are few neurological conditions for which thetreatment is simple and often dramatically effective but themethods of reaching the diagnosis remain controversial.Even the conventionally accepted name of normal-pressurehydrocephalus (NPH), introduced by Hakim in 1964, ismisleading because hydrocephalus in the proven absence ofa raised resting intracranial pressure is a feature of severalother conditions-eg, cerebral atrophy, multiple infarcts,Alzheimer’s disease, and hypertensive encephalopathy. Theclassic triad of progressive dementia, gait disturbance, andurinary incontinence is as likely to occur in any of these morecommon disorders as in NPH, so differentiation on the basisof clinical criteria alone is most unwise.

It is necessary to select a group of patients who wouldhave a good chance of responding to permanent drainage ofthe cerebrospinal fluid (CSF) through a ventriculoatrial orventriculoperitoneal shunt. With the introduction of higherdefinition computed tomographic scanning in the pastdecade, it had been hoped that recognition of periventriculartranslucency and disproportionately narrow surface sulci atthe vertex of the hemispheres, in addition to the classicclinical features, would resolve the diagnostic difficulty. Fora small subgroup of patients with a previous head injury,cranial surgery, subarachnoid haemorrhage, or a bout ofmeningitis and for another subgroup with a short history orradiological evidence of enlarging ventricles, this selection isbelieved by many to be acceptable, with over a 40% chanceof successful response to a shunt. However, most patientsreferred to neurologists have a history of many months withtwo or three of the clinical triad, some of the radiologicalfeatures of NPH, and no known relevant history. In suchcases, the success rate of CSF drainage is less than 15 %, andjust below the incidence of postoperative complications.Subjecting all these patients to a shunt procedure would bedeemed indiscriminate.

Faced with this dilemma, a group of neurosurgeons inCopenhagen lately asked the Alfred Benzon Foundation toassemble a group of basic scientists and clinical researchersfrom nine countries to discuss openly the terminology,diagnosis, and treatment of this condition and to share theirexperiences of studying the disorders of CSF circulationimplicated in this and other neurological conditions.!

There was unanimous agreement about the principlesunderlying the pathophysiology of NPH. Any defect in themain exit channels from the CSF pathways to the venouscirculation at the cranial arachnoid villi will cause an increasein resistance to outflow. Most fluid normally passes throughextracellular intraendothelial clefts, but with increasingCSF pressures, micropinocytotic vesicles respond byenlarging and fusing to create transcellular channels. If thearachnoid space is contaminated by red cells as a result ofhead injury, surgery, or subarachnoid haemorrhage,fibrinogen is converted to fibrin, encouraging deposition of aprotein net. This net impedes the circulation of CSF overthe hemispheres and the villi become clogged.

A substance present in whole blood and plasma but not inserum or dialysate interrupts transendothelial vesicular

transport and further raises the overall outflow resistance.Pressure gradients are created between formation and

absorption sites, and it is the transmantle gradient that maywell contribute to the dilatation of the ventricles either

acutely or several months later. Although villus changesoccur after meningitis, structural changes have not beenreported in idiopathic NPH and the defect in absorptionremains a mystery.

Previously, isotope and pneumoencephalography wereused to demonstrate the supposed changes in CSF flowpatterns. Others have monitored intracranial pressure for 24hours to observe the frequency of B waves, which are morecommon in these patients. Such indirect measurements donot add any diagnostic information to the clinical and

radiological features. At the Copenhagen symposium, theassembled company unanimously favoured estimating theinfluence of the pathological process on CSF circulation bymeasuring outflow resistance in patients with suspectedidiopathic NPH. Most agreed that if the outflow resistancewas less than 11 mm Hg/ml per minute, a shunt was unlikelyto help. The higher the resistance above this level, thegreater was the chance of clinical improvement withshunting, with probabilities ranging from 25% to 80%.

The methods of measurement used varied from centre tocentre. In one series of over 2000 patients, access to the CSFcirculating system was by the lumbar route, but it wasessential that the arachnoid should not be penetrated morethan once to prevent extravasation of CSF during the testthrough previous puncture holes. Most workers preferredventricular access, despite the slight risk of infection. Abolus technique is simple and quick, but in unanaesthetisedpatients the resistance is underestimated because the boluscauses a pressure overshoot due to transient vasodilatation,and reproduciblity is then poor. Continuous infusions ofRinger lactate to produce a series of steady states, either byconstant flow or by constant pressure, proved very

reproducible and compared favourably with the mostcomplex technique, by which electronically regulatedinfusions were used to achieve rapid stabilisation, withcomputer modelling to allow volume accounting.

Despite the general agreement on the practical issuesrelating to normal-pressure hydrocephalus, the thirty-oneparticipants suggested thirty-one "more appropriate"alternative names for this syndrome.

1. Gjerris F, Borgesen SE, Sorensen PS, eds. Outflow of cerebrospinal fluid.Alfred Benzon Symposium 27. Copenhagen: Munksgaard, 1989.