Prevalence of gall stones in Dundee: a necropsy study.

Necropsy records from two large general hospitals in Dundee showed short-term fluctuations in the prevalence of gall stones that had not previously been described. There was no evidence of a rise in the standardised prevalence rate between 1902-9 and 1953-73. A spurious increase was apparent from the crude prevalence rates for these periods, which resulted simply from the increased age of the patients in the later period. Since there was no real increase in prevalence no conclusions can be drawn about dietary or other changes. Patients with stones in the common bile duct were likely to die from an associated cause. This related mainly to a high mortality rate in women. In patients with established epilepsy the prevalence of gall stones was greater than expected, which suggests that phenobarbitone does not diminish the likelihood of gall stones.     

Effect of vegetarianism on development of gall stones in women.

Real time ultrasonography was used to compare the prevalence of gall stones in two groups of women aged 40-69: 632 women recruited from general practice registers and 130 vegetarians. One hundred and fifty-six (25%) of the 632 women who ate meat and 15 (12%) of the 130 vegetarian women either had gall stones visible on ultrasonography or had previously undergone cholecystectomy (p less than 0.01). The prevalence of gall stones was found to increase with age and body mass index. The 2.5 fold increase in risk of developing gall stones in non-vegetarians compared with vegetarians was reduced to 1.9 when controlling for these two potentially confounding factors, but remained significant. A family history of gall stones was reported more often by women with gall stones, but no association was found with parity or use of exogenous oestrogens. Thus the importance of age and obesity to determine the prevalence of gall stone was confirmed, and a dietary factor associated with vegetarianism may prevent this common condition.     

Annual cyclicity of gall stone prevalence in deer mice (Peromyscus maniculatus gambelii)

The prevalence of gall stones (100% cholesterol) in a deer mouse (Peromyscus maniculatus) population located in Siskiyou County, California (USA) was studied on a monthly basis from February 1985 through January 1988. During each year we documented a pronounced annual cyclicity with peak prevalence (31 to 53%) during the winter and low prevalence (2 to 3%) during late summer. Gall stone prevalence was not related to sex or age of the animal. The earliest onset of gall stone production and the maximum prevalence achieved were associated with the greatest abundance of deer mice; lower levels of population abundance were associated with later onset of gall stone production and lower peak prevalences. This association of gall stone prevalence with both season and population abundance levels suggests that the causative factor(s) is/are related to the quality and availability of the diet.     

Gall stones in sickle cell disease in the United Kingdom.

The prevalence of gall stones was studied prospectively by abdominal ultrasound examination in 131 patients with sickle cell disease aged 10-65 years. Of 95 patients with homozygous sickle cell disease, 55 (58%) had gall stones or had had a cholecystectomy. Gall stones were present in four out of 24 (17%) patients with haemoglobin S + C disease and two out of 12 (17%) with haemoglobin S beta thalassaemia. The presence of gall stones was not related to sex, geographical origin, or haematological variables and was not associated with abnormal results of liver function tests. Symptoms typical of biliary colic were reported by 32 out of 47 adult patients with gall stones, and cholecystitis or cholestasis was diagnosed in 18. Cholecystectomy was performed in 29 patients with good relief of symptoms in most cases. Postoperative complications were common, occurring in 10 of the 28 patients who could be evaluated, but not generally serious; they were considerably lessened by a preoperative exchange transfusion that reduced the haemoglobin S concentration to below 40%. It is suggested that all patients with sickle cell disease should be screened for gall stones and that elective cholecystectomy should be performed in those with symptoms or complications.     

Intermittent Secretion of Abnormal Bile in Patients with Cholesterol Gall Stones

Gall bladder and hepatic bile was sampled from 66 patients undergoing elective operations on the biliary tract. Fifty-one patients had cholesterol gall stones but only 59% of these were found to have bile which was supersaturated with cholesterol. Repeated sampling of hepatic bile from patients with T-tubes showed that the secretion of supersaturated bile was intermittent.These results indicate that it is impossible to separate patients with cholesterol stones from controls simply by examination of the lipid composition of their bile, since an appreciable number of bile samples from patients with cholesterol stones were unsaturated.The fact that cholesterol gall stones form when the bile is supersaturated with cholesterol only intermittently suggests that the gall bladder may also have a part in their formation.     

Migration of gall stones.

The factors influencing the migration of gall stones are ill understood. Altogether 331 patients undergoing cholecystectomy were studied prospectively. The diameters of the cystic and common bile ducts and of stones in the gall bladder and bile ducts were measured. Increasing pressure was applied to the freshly excised gall bladder in an attempt to evacuate stones through the cystic duct. Stones passed in 33 (60.0%) of patients with choledocholithiasis, 45 (67.2%) of patients with pancreatitis, and 7 (3.2%) of patients without either pancreatitis or choledocholithiasis. Stones migrated in 6 (3.0%) who had a normal cystic duct diameter (less than or equal to 4 mm) and in 46 (32.5%) with a duct over 4 mm diameter. Common bile duct stones were often larger than the diameter of the cystic duct and when reintroduced into the gall bladder would not migrate. The passage of debris (less than or equal to 1 mm) through the cystic duct bore no relation to the presence or absence of choledocholithiasis or a dilated cystic duct. Small stones (1-4 mm diameter) must migrate to initiate and facilitate further migration; some must increase in size in the common bile duct. Increased biliary pressure consequently dilates the duct system retrogradely, allowing larger stones to follow. Patients at risk of stone migration and thereby pancreatitis and jaundice have large ducts that can be detected by ultrasound assessment.     

Prediction of gall-stone pancreatitis by computer.

The clinical features at presentation of 53 patients admitted with primary acute pancreatitis due to gall stones were compared with those of 31 patients in whom the disease was due to other causes. Between these two groups 10 significant differences existed. By listing the frequency of symptoms and signs for each group a computer data base was prepared and incorporated into a program used in the differential diagnosis of acute abdominal pain. A program written to predict the presence of gall stones in patients with acute pancreatitis was accurate in 92% of the patients studied. A predictive index devised from the presence of three of the significantly differing clinical features correctly identified 82% of patients with gall-stone pancreatitis. Predicting the presence of gall stones on admission by analysing the presenting symptoms and signs with a computer had an accuracy comparable to that of ultrasonography or radiology and may be of value in the management of patients with acute pancreatitis.     

Looking for gall bladder disease in the patient's iris.

In alternative health care iridology is used as a diagnostic aid. The diagnosis of gall bladder disease was used to study its validity and interperformer consistency. The presence of an inflamed gall bladder containing gall stones is said to be easily recognised by certain signs in the lower lateral part of the iris of the right eye. Stereo colour slides were made of the right eye. Stereo colour slides were made of the right eye of 39 patients with this disease and 39 control subjects of the same sex and age. The slides were presented in a random order to five leading iridologists without supplementary information. The prevalence of the disease was estimated at 56%. The median validity was 51% with 54% sensitivity and 52% specificity. These results were close to chance validity (iota = 0.03). None of the iridologists reached a high validity. The median interperformer consistency was 60%. This was only slightly higher than chance consistency (kappa = 0.18). This study showed that iridology is not a useful diagnostic aid.     

Postprandial gall-bladder emptying in patients with gall stones.

Gall-bladder emptying in response to a standard meal was assessed in 34 patients with radiolucent gall stones and 34 matched controls. Percentage gall-bladder emptying, derived from volume measurements made on standardised oral cholecystography, was significantly higher at 15 minutes in the patients than the controls (mean +/- SE of mean 38.0 +/- 3.7% v 28.0 +/- 3.8%). This difference was maintained at 30 and 60 minutes. It is concluded that postprandial gall-bladder emptying is increased in patients with cholesterol gall stones, and that this may be the cause of the small bile-acid pool found in these patients.     

Gall stone dissolving agents.

During the decade in which the medical dissolution of gall stones has become feasible several drugs have been introduced but only the two listed in the British National Formulary have been intensively evaluated and shown to be effective--chenodeoxycholic acid and the closely allied ursodeoxycholic acid. The dissolution of gall stones was last reviewed in the "BMF" in 1976, at which stage experience with chenodeoxycholic acid was limited. Since then the indications and potential for this bile acid in treating gall stones have become better understood, and data on the newly introduced ursodeoxycholic acid are being evaluated. Cholesterol, but not pigment, gall stones are amenable to oral dissolution treatment. This review will cover firstly, chenodeoxycholic acid, secondly, ursodeoxycholic acid, then a comparison of the two drugs, an assessment of the place of medical dissolution in the management of gall stones, and, finally, the dissolution of stones in the common bile duct.     

Gall-stone dissolution and recurrence: are we being misled?

Oral cholecystography repeated at six-months intervals is the standard method for determining reduction in size of gall stones (partial success) and complete dissolution of stones (complete success). In a comparative study of oral cholecystography and cholecystosonography six out of 14 patients with gall stones achieving complete success by oral cholecystographic criteria had stones still detectable by ultrasonography. Repeat oral cholecystography in a further 11 patients receiving post-dissolution maintenance treatment detected stones in two, whereas ultrasonography detected stones in seven. In future complete dissolution of gall stones should be reported only if both oral cholecystography and ultrasonographic studies give negative results and the progress of patients receiving post-dissolution maintenance treatment is monitored by ultrasonography rather than serial oral cholecystography.     

Oral contraceptives,pregnancy, and endogenous oestrogen in gall stone disease--a case-control study.

A case-control study of gall stone disease in women in relation to use of contraceptives, reproductive history, and concentrations of endogenous hormones was undertaken. The study population comprised 200 hospital patients with newly diagnosed gall stone disease, 182 individually matched controls selected from the community, and 234 controls who were patients in hospital. Use of oral contraceptives was associated with an increased risk of developing gall stones among young subjects but a decreased risk among older subjects. The risk of developing gall stone disease increased in association with increasing parity, particularly among younger women. The risk fell with increasing age at first pregnancy, independent of parity. Mean urinary excretion over 24 hours of oestrone, but not of pregnanediol, was significantly (p less than 0.05) greater for postmenopausal patients than controls. The age dependence of the relative risk associated with exposure to oral contraceptives and pregnancy suggests that there are subpopulations of women susceptible to early formation of gall stones after exposure to either oral contraceptives or pregnancy.     

Effects of gall volume on survival and fecundity of gall-making aphidsAdelges japonicus (Homoptera: Adelgidae)

The number of larvae reaching maturity within the gall of Adelges japonicus was positively related to gall volume, and the relationship between the number of mature larvae and gall volume did not change with different densities of colonized larvae. The population changes in the bud galls of A. japonicus were surveyed by collecting the galls, which did not suffer predation or parasitism within the galls, from young artificial plantations of Picea jezoensis over two years. In the year when the density of colonized larvae was high, they suffered a 42% mortality within the galls, whereas mortality was nearly zero in the low density year. The numbers of larvae per gall were positively correlated with gall volume. The regression lines of the number of colonized larvae on gall volume did not differ significantly in the regression coefficients between the two years, whereas the intercept was significantly higher in the year when the density of colonized larvae was higher. However, different within-gall mortality nullified this difference, and the regression lines of the number of mature larvae on gall volume had no significant difference both in the regression coefficients and the intercepts. This suggests that the number of mature larvae per gall was limited by available resources within the gall which were positively related to gall volume. In 25% of the galls in which mature larvae inhabited, the space within the galls were completely filled by the larvae, indicating that space was one of the limiting resources. Gall volume also affected the number of adults that emerged from the gall and the potential number of their progeny.     

Pilot study of combination treatment for gall stones with medium dose chenodeoxycholic acid and a terpene preparation.

Thirty patients with radiolucent stones in a radiologically functioning gall bladder were treated for up to two years with a combination of Rowachol (one capsule twice daily), a mixture of cyclic monoterpenes, and chenodeoxycholic acid (7.0-10.5 mg/kg/day). The patients were not selected for body weight or size of stones. All complete dissolutions diagnosed by oral cholecystography were confirmed or refuted by ultrasound examination. Control of symptoms was excellent, only one patient withdrawing from the study because of persistent biliary pain. No evidence of hepatotoxicity was detected biochemically, and diarrhoea due to chenodeoxycholic acid was minimal at this dose. Stones disappeared completely in 11 patients (37%) within one year and in 15 (50%) within two years. These results compared favourably with those obtained with similar doses of chenodeoxycholic acid alone, in particular those of the National Co-operative Gallstone Study (complete dissolution in 13.5% of patients at two years). Treatment with a combination of medium dose chenodeoxycholic acid with Rowachol for radiolucent gall stones is economical, effective, and likely to minimise persistent symptoms and adverse effects of treatment.     

Increasing Frequency of Gall Bladder Operations in the Bristol Clinical Area

In the Bristol clinical area the frequency of gall bladder operations rose by a factor of 3·4 between 1940 and 1970, the greatest increase occurring in the 1950s. The increase took place in all age groups, but was greatest in the under-30s and in men. Numerous factors affect the chance of a patient with gall stones being operated on, but a change of this magnitude suggests there has been a substantial rise in the incidence of gall stones since the second world war. This belief is supported by data from the nationwide Hospital In-patient Enquiry.     

Diet,alcohol, and relative weight in gall stone disease: a case-control study.

A case control study of gall stone disease in relation to diet, alcohol, and relative weight was undertaken. The study population comprised 267 hospital patients with newly diagnosed gall stone disease, 241 individually matched controls selected from the community, and 359 controls who were patients in hospital. Dietary intake was estimated with a quantitative food frequency questionnaire. Multiple logistic regression analysis was used to estimate the net association between individual nutrients and the risk of formation of gall stones. Variations in risk with sex and age were examined in the light of prior evidence of influences of sex hormones and age on hepatobiliary metabolism. In both sexes increased intake of alcohol was associated with a decreased risk of developing gall stones; increased intake of simple sugars in drinks and sweets was associated with an increased risk; and increased intake of energy or fat was associated with an increased risk in young subjects. Obesity was associated with an increased risk only in young women.     

Percutaneous cholecystolithotomy

A percutaneous method was used to remove stones from otherwise normal gall bladders, as assessed by cholecystography and ultrasonography. The procedure was performed in a single stage under general anaesthesia, adopting the method and instruments used for one stage percutaneous nephrolithotomy. A Foley catheter was left in the gall bladder and the system checked with contrast at 10 days to ensure free drainage and exclude residual calculi. Seven out of eight patients had a successful percutaneous cholecystolithotomy. An adequate track could not be secured in one man; he had an uneventful cholecystectomy under the same anaesthetic. Follow up at three months of the seven patients showed no calculi and no complications.Percutaneous cholecystolithotomy may prove complementary to extracorporeal shockwave lithotripsy in patients in whom there is difficulty focusing the shock waves on the gall bladder or who have had incomplete disintegration of stones.     

Gall-bladder sensitivity to cholecystokinin in patients with gall stones.

Gall-bladder sensitivity to cholecystokinin (CCK) was determined by dynamic cholescintigraphy in 18 patients with radiolucent gall stones and 18 matched controls during an infusion of CCK in which the rate of infusion was increased. In 10 of the matched pairs the patient was more sensitive than the control, in one the control was more sensitive, and in seven no difference was detected (p = 0.012). It is concluded that patients with cholesterol gall stones have increased gall-bladder sensitivity to CCK, and that this may be important in the pathogenesis of this disease.     

Gall Stones in Patients with Disorders of the Terminal Ileum and Disturbed Bile Salt Metabolism

In a combined historical and radiological survey gall stones were found in 23 out of 72 patients with disorders of the terminal ileum (31·9%). This is four to five times the expected incidence of cholelithiasis. In these patients the incidence of gall stones was not related to age, but did, however, increase with increased duration of the ileal disorder. Glycine/taurine conjugation ratios of bile salts in the bile were abnormally high in 10 out of 11 patients with ileal disorders. Both impaired bile salt recirculation and absorption of poorly soluble bacterially degraded bile salts are possible causes of cholelithiasis in these patients.     

Host plant effects on the development and survivorship of the galling insect Neopelma baccharidis (Homoptera: Psyllidae)

In this study, the mortality factors acting upon the galling psyllid Neopelma baccharidis Burckhardt (Homoptera) caused by its host plant, Baccharis dracunculifolia De Candole (Asteraceae) were analysed. In March 1999, 982 galls of the same cohort were randomly marked on 109 individuals of B. dracunculifolia in the field. Galls were censused each month during their development, from April to August, and dead galls were collected and analysed for mortality factors. Gall dehiscence rates were calculated for each month. The major mortality source of N. baccharidis was gall dropping (13.2% of the original cohort), which is probably a normal outcome of previous mortality caused by the other factors observed in this study. Unknown factors killed 11.7% of this gall population and were ascribed to plant resistance during gall development. Empty galls represented 7.7% of the observed mortality and may be a consequence of egg retention or egg mortality/abortion related to variations in plant quality. Shoot mortality was high during the dry season and killed 7.5% of the galls, but this impact was minimized after the third month from gall formation due to the ability of nymphs to accelerate development and emerge from galls on dying shoots. However, the size of dehisced galls on dead shoots tended to be smaller, possibly affecting adult performance. Mortality of N. baccharidis attributed to B. dracunculifolia strongly controlled the galling insect population, killing 40.7% of the original cohort of galls. Plant‐mediated mortality was caused by often neglected factors acting predominantly during the first 3 months of development, which are critical to gall survivorship. These results reinforce the importance of bottom‐up forces in plant‐insect systems.