By Author
  By Title
  By Keywords

April 1984, Volume 34, Issue 4

Original Article

Bladder Stone Disease in Children: Clinical Studies

S.A. Anwar Naqvi  ( Department of Urology Dow Medical College and Civil Hospital, Karachi. )
S. Adibul Hasan Rizvi  ( Department of Urology Dow Medical College and Civil Hospital, Karachi. )
S. Shahjehan  ( Department of Biochemistry, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi. )

Abstract

One hundred eighty children with bladder stone disease (BSD) and 50 normal children were studied between July 1979 and June 1982.
The peak age group in BSD children was between 2-4 years and the male to female ratio was 9:1. Hospital reporting of stone formers showed no significant relationship to mean monthly temperature or relative humidity.Painful micturition was the commonest clinical presentation (71.7%). Twenty patients had associated renal disease and associated upper tract calculi were not commonly seen (3.3%). Radiology provided definitive diagnosis of bladder stones in 95% patients.
One hundred fifty eight stone formers underwent operative procedures for removal of stones. The occurrence of complications was significantly higher in children with co-existing urinary tract infection. Operative mortality was 0.6%. In 61% BSD children the probable etiological factors predisppsing to stone formation could not be detected. On follow-up the recurrence rate was found to be 1.l%.(JPMA 34:94,1984).

Introduction

Archaeological discoveries provide sufficient proof for the assumption that vesical calculi in children occurred since antiquity (Anderson, 1972 cited by Van Reen, 1981). The high prevalence of childhood bladder stones has been documented in Europe and North America in the 18th and 19th century (Yelloly, 1829; Cummings, 1977). At the turn of the century, however, the geographical foci of childhood BSD shifted to the East, stretching in a broad belt from Egypt through Iran, Pakistan, India, Thailand, to Indonesia (Halstead, 1977; Thalut et al., 1976; Van Reen, 1981). However, sources in literature also indicate that incidence of upper tract calculi in children from Turkey, China and Phillipines is rising although endemic calculi were common in these countries fifty years ago (McLaren, 1963; Remzi et al., 1980; Dajani et al., 1981; Blacklock, 1982)
McCarrison (1931) provided the first epidemiological data on urinary stone disease in Indo94 Pak sub-continent. Several workers have shown the clinical importance of urolithiasis in Pakistan (Ilahi, 1967; Shahjehan and Rahman, 1971; Rizvi, 1975; Khan, 1977; Rahman and Van Reen, 1981). Although there is agreement that childhood urolithiasis in our country is predominently of lower urinary tract type, a need was felt to study the problem in greater detail. The present study is an attempt in this direction.

Material and Methods

One hundred eighty consecutive phildren upto the age of twelve years, admitted with bladder stone disease (BSD) in Urology ward of Civil Hospital, Karachi between July, 1979 and June, 1982, were included in the study. Fifty healthy children drawn from the relations of BSD children with a similar age, sex, ethnic and socio-economic background were included in the study as controls.
The diagnosed patients were admitted and their clinical and dietary history was recorded on a proforma. Detailed clinical examination was undertaken in both the patients and controls. Laboratory investigations include4 urinalysis and complete blood picture. A 24 hours urine sample was collected for estimation of volume, specific gravity and pH. The serum studies included total proteins (Reinhold, 1953, cited by Varley, 1969), blood urea (D.iacetyl method, cited by Wooten, 1974) and serum electrolytes (Varley, 1969). Serum and 24 hr urinary calcium (Bauer et al, 1962) inorganic phosphate (Gomori, 1942, cited by Varley, 1969) uric acid (Caraway, 1963 cited by Varley) were estimated.
Radiological investigation included plain film of abdomen (KUB). Intravenous Urography (IVU ) was done where plain x-ray was equivocal in the presence of strong presumptive evidence of bladder stones. Endoscopy was done in those patients where clinical and radiological evidence indicated lower tract obstruction.
The patients underwent cystolithotomy for removal of stones. In those where the stone had got impacted in urethra on its descent from bladder, a urethrolithotomy was undertaken.
The children were followed up after a month and then at yearly interval unless they had any symptoms when they were asked to come immediately.

Results

The patients came from all parts of the city although the majority came from underdeveloped areas where most civic amenities were severely lacking. These BSD children constituted 15.8% of urological admissions, 51% of paediatric urological admission and 70.4% of paediatric urolithiasis cases during the period of study (fig 1).

There were 162 male and 18 female stone formers in the study ranging from one to twelve in age. The peak age group in stone formers was between 2 - 4 years and male to female ratio was 9 1 (fig 2).

Most of the children were from families belonging to lower socio-economic group (88.4%) and only 11.6% stone formers were from middle or upper income group.
August was the month of peak reporting of stone formers to the hospital (20 children ) while only 6 children were admitted in September. There was no significant relationship between monthly admission and either the mean monthly temperature or the mean monthly humidity (fig. 3).


Painful micturition was the commonest clinical presentation (71 .7%) while macroscopic haematuria was seen in 24.4% cases. Milking of penis was most frequently seen in males below the age of 6 and in older children this symptom was less frequent, the difference being highly significant (P <0.001) (table 1).

A significantly higher (P < 0.05) occurrence of intermittent retention was seen in children where the duration of symptoms was 0-6 months compared to the group with duration of symptoms of more than 6 months. No correlation could be found between the occurrence of symptoms to the incidence of urinary tract infection or urinary pH in the stone formers.
On clinical examination suprapubic tenderness was positive in 73 (40.5%) stone formers (table II).

Stone was felt per urethra in 1 2 children and palpable per rectum in 2.7% cases. In 54.4% stone formers no physical signs attributable to stone disease could be found. Twenty children harboured other renal pathologies. Seven children on admission had evidence of renal failure (table III)


Definitive diagnosis of stone in urinary bladder was made on plain X-ray or abdomen in 164 (89.4%) children intravenous pyelography in 5.5% and endoscopy in 3 children. Spontaneous passage of documented bladder stone was found to be the basis of diagnosis in 6 children.. Positive family history of lithiasis was found in 11 children (7 in siblings and 4 in parents).
One hundred fifty formers underwent surgery (table IV).

Two children recurrence of bladder stone. eight (87.8%) stone for removal of stones were reoperated for Suprapubic cystolithotomy was undertaken in 153 (85%) children and urethrolithotomy in 5 patients. In 8 children the stone passed out spontaneously. Ten stone fonners either refused surgery, left against medical advise or were not operated.
Of 158 children who were operated, 52 (33%) showed complications. One child succumbed on the first post-operative day due to chest complication. Wound infection was the commonest complication (15.8%) followed by suprapubic leakage (8.8%). Thirty five patients with complications had positive urine culture against 19 children who had no complications but had positive urine culture, the difference being highly significant (P < 0.001) (table V).


On correlating the complications with serum protein and blood urea level in stone formers, no significant relationship could be seen.
In 110 stone formers no predisposing factors for stone formation could be detected within the limits of the protocol of investigation (table V). Fifty two children showed some metabolic cause attributable to the formation of calculi. Urinary stasis was seen in 5% patients. One child had a foreign-body stone, formed on a piece of retained rubber catheter.
On follow-up none of the 12 children who passed stone spontaneously returned after treatment. Of the 158 children who underwent surgery, 35 were lost to follow-up. One hundred twenty three (68.3%) patients attended outpatients regularly. Two were operated for upper tract calculi. Seven patients showed urinary tract infection which settled on appropriate treatment. Two children on whom urethrolithotomy was done, were attending stricture clinic on the conclusion of the study.

Disaission

In the present series the proportion of BSD children amongst the paediatric urolithiasis was 70.4% which was earlier reported to be 84.8% by Rizvi (1975) and 95% by Ilahi (1967). A similar proportion (77.6%) was reported in Egyptian children (Loutfi et a!., 1972). In Iran the proportion of BSD cases among all paediatric urolithiasis appear to have shown a decrease from 69% to 58.8% over the last ten years (Gharib, 1970; Sadre et al., 1973; Halim et aL, 1981). In India this proportion shows little change (from 85% to 87%) in Northern and Eastern regions (Andersen, 1962; Aurora et al., 1970; Singh et al., 1978). The pattern of childhood urolithiasis in Pakistan as well as in the neighbouring countries is derived from hospital based data whose bias in interpretation of the prevalence of disease is well known (Barker and Donnan, 1978; Williams, 1978; Scott et aL, 1981). Nevertheless, the pattern of paediatric urolithiasis appears to be undergoing some change in developing countries as well, more so in urban areas (Sutor, 1980), which may be an expression of regional specificities. It remains to be seen if change in the face of childhood urolithiasis, as seen in the west at the turn of the century, can be anticipated in Afro-asian countries, with achange in the socio-economic development in these countries.
The peak age group in BSD in the present study was between 2-4 years. Most of the workers from Egypt, Turkey, Iran, India, Thailand and Indonesia have reported similar findings (Eckstein, 1961; Valyasevi and Van Reen, 1968; Gharib, 1970; Aurora et al., 1972; Sadre et al., 1973; Thalut et al., 1976). This draws attention to the hypothesis that occurrence of bladder stones in these children may be a very early event (Haistead, 1977) and whether it relates to the age of weaning remains to be seen.
The number of male children suffering from BSD was much higher than females with a male to female ratio of 9:1 in the present study. This is in agreement with the reports from Turkey (11.9:1), Thailand (10:1), Indonesia (12:1) and Pakistan (8.5: 1) (Eckstein, 1961; Haistead and Valyasevi, 1967; Thalut et al., 1976; Rahman and Van Reen, 1981). A much higher prevalence of bladder stone disease in males has been reported from Northern India and Egypt, with male to female ratio ranging from•15.6:1 to 31:1 (Andersen, 1962; Aurora et al., 1970; Aurora, 1977; Loutfi and Abdel-Hamid, 1977). The male to female ratio in childhood urolithiasis in series from western countries varies between 1 .1 and 1:2 the predominance of childhood upper tract calculi in these countries being well documented (Myers, 1957; Ghazali et al.,1973; Malek, 1976; Churchill et al., 1980). Some workers have attempted to explain the male predominence on the basis of long tortuous urethra in male (Loutfi et al., 1972; Aurora, 1977). However, if it was only a question of passage of microlith the greater laxity and width of female urethra (Finlayson, 1977) may be of0greater relevance than the length of urethra.
Many workers consider high environmental temperature and humidity to be important contributory factors in the occurrence of renal/ureteric colic (Prince and Scardino,1960; Bateson, 1973; Elliot et a!., 1975; Fujita, 1979). Although a greater number of cases (102) were seen from March to August as compared to 78 cases seen between September and February, the difference was not statistically significant. This is in agree. ment with earlier reports which showed no significant seasonal relationship to the time of hospital reporting of BSD children (Andersen, 1962; Loutfi et al., 1974; Sastraomidjojo, 1977). There is need for further study of the relationship of temperature and humidity with the aggravatiQn of symptoms to a degree that these children seek medical help, although the stones have been present for a long time.
Many workers have reported a similar over all pattern of presenting symptoms (table 1) as shown in the present study with painful micturition being the commonest (Aurora et aI.,1970; Gharib, 1970; Khan, 1977; Teotia and Teotia, 1977). In younger age group (0-6 years) milking of penis was significantly more frequent than in older children while the intermittent obstruction was also significantly more common in the group with lesser duration of symptoms (table 1 ). Thalut and associates (1981)also found pulling penis to be the commonest symptoms in male children. It is probable that irritation of trigone by the smaller calculi together with its ball-valve action causes obstruction to the flow of urine and the child pulls at the penis to relieve both the obstruction and the irritation of the bladder neck.
Older children with larger stones are less likely to face this situation.
Haematuria was seen in 24.4% cases which is in agreement with reports from Thailand, Indonesia and India (Haistead and Valyasevi, 1967; Thalut et al., 1976; Teotia and Teotia, 1977). However, this is in contrast to childhood renal lithiasis where the frequency of haematuria ranges from 5 5-80% (Gaches et al., 1975; Puga et al., 1977; Noronaha et al., 1979). Whether this is due to the much richer blood supply of the kidney or greater area of mucosal contact of the stone in case of renal calculi needs further clarification.
Evidence of associated renal disease was seen in 20 (15.6%) patients. The Occurrence of upper tract calculi in childhood during the period of study was 23.5% and the cases of concomitant upper and lower tract calculi were 10% of all upper tract calculi. The probability that these concomitant cases are incidental overlap is quite low (P < 0.01 > 0.05). Thus the view that most of the bladder calculi have renal origin cannot be ruled out and there is still a need to consider BSD in the broader frame work of urolithiasis.
Majority of BSD cases (61.1%) in the present study showed no attributable cause for stone formation which agrees well with reports of idiopathic calculi in children from developing countries (Haistead and Valyasevi, 1967; Sadre and Ziai, 1977; Singh, 1977; Rahman and Van Reen, 1981; Brockis et al., 1981). In the present study stasis was shown to be a possible etiological factor only in 5% children, whereas some workers reported a higher percentage (Aurora et al., 1970; Taneja et al., 1970; DuPreez arid Cremin, 1973; Loutfi et al., 1974).. This may be because intravenous pyelography was done only in equivocal cases where plain x-ray despite presumptive symptoms was negative for bladder stone. In the present study 52 (28.9%) patients showed some metabolic’ disorder which could predispose to stone formation. This is in contrast to low reported incidence of metabolic causes for vesical calculi in Indian children (Aurora et al., 1970). There is a need for an indepth investigation of metabolic causes in these children in our region.
There was a significantly higher frequency of post-operative complication in the presence of urinary tract infections. In view of this a preoperative urine culture and appropriate treatment is strongly advocated to avoid this situation. It is also important to note that a stone needs to be removed suprapubically because of the complications that ensues on its impaction in the urethra (Malek, 1976; Drach, 1978). Some workers (Loutfi 1977; Singh et aL, 1968) have recommended closure of bladder leaving no uretheral catheter postoperatively. However, in our experience a catheter in the immediate postoperative period (12-24 hours) was beneficial as the child was likely to retain urine due to postoperative pain. This increased the likelihood of producing pressure on bladder repair thereby increasing the frequency of suprapubic leakage of urine.
Low recurrence rate following surgery (1 .2%) in the present study agrees well with other workers who have studied the problem of bladder stone disease in children (Valyasevi and Van Reen, 1968; Aurora et al., 1970; Loutfi, 1977; Brockis et al., 1981). This is in contrast to a recurrence rate of upto 30% for renal calculi in children (Deaschner et aL, 1960; Gaches et al., 1975; Malek and Kelalis, 1975). The low recurrence rate in childhood BSD appears to be attributable to some stone promoting events which have occurred in the remote past as an episode. Since the underlying factors do not persist, unlike renal stones, the stone forming process does not show the same activity as in upper tract calculi.

Acknowledgements

We wish to thank all the members of urology unit for theft help in the management of these cases and Mr. Rafiullah and Miss Cassie for typing the manuscript.

References

1. Andersen, DA. (1962) The nutritional significance of primary bladder stone. Br. J. Urol., 34:160.
2. Andersen, D.A. (1972) cited by Van Reen, R. Geographical and nutritional aspects of endemic stone, in urinary calculus; international urinary conference. Edited By J. Gwynne Brockis and Birdwell Finlayson. Littleton, PSG Publishing, 1981, p. 177.
3. Aurora, A.L. Vesical calculus disease of childhood, in idiopathic urinary bladder stone disease. Sponsored by the Joint E. Fogarty International Center. Edited by Robert Van Reen. Washington, DHEW Publication, 1977, p. 215.
4. Aurora, A.L., Taneja, O.P. and Gupta, D.N. (1970) Bladder stone disease of childhood. I. An epidemiological study. Acta Paediatr. Scand., 59: 177.
5. Barker, J.P. and Donnan, S.P.B. (1978) Regional variation in the incidence of upper urinary tract stones in England and Wales. Br. Med. J., 1:67.
6. Bateson, E.M. (1973) Renal tract calculi and climate. Med. J. Aust., 2:111.
7. Baner, J. D., Toro, G. and Ackermann, F.C. Bray’s Clinical Laboratory methods. 6th ed. St. Louis, Mosley, 1962. P. 310.
8. Blacklock, N.J. Urolithiasis; epidemiology, in scientific foundation of urology. Edited by Geoffrey D. Chisholm and David Innes Williams. 2nd ed. London, Heineinann, 1982, p. 251.
9. Brockis, J.G., Bowyer, R.C., McCulloch, R.K., Taylor, TA., Wjsniewshi, Z.S., Kamardi, T. and Rizal, A. Physiopathology of endemic bladder stones in urinary calculus, international urinary stone conference. Edited by J. Gwynne Brockis and Birdwell Finlayson. Littleton, PSG publishing, 1981, p. 225.
10. Churchifi, D.N., Maloney, C.M., Nolan, R., Gault, M.H. and Winsor, G. (1980) Pediatric urolithiasis in the 1970s. J.Urol., 123:237.
11. Cummings, N.B. Overview of bladder stone disease, in idiopathic urinary bladder stone disease. Sponsored by John F. Fogarty International Center. Edited by Robert Van Reen. Washington, DHEW Publication, 1977, p.1.
12. Daeschner, C.W., Singleton, E.B. and Curtis, J.C. (1960) Urinary tract culculi and nephrocalcinosis in infants and children. J. Pediatr., 57: 712.
13. Dajani, A.M., Bjornesjo, K.B. and Shehabi, A.A. Urinary stone disease in Jordan, in urinary calculus; international urinary stone conference. Edited J. Gwynne Brockis and Birdwell Finlayson. Littleton, PSG Publishing, 1981, P. 35.
14. Drach, G.W. Urinary lithiasis, in Campbell’s urology. Edited by J. llartwell Hanson et al. 4th ed. Philadelphia, Saunders, 1978, vol. l,p. 779.
15. DuPreez, H.M. and Cremin, B.J. (1973) Urinary calculi in childhood; a clinical and radiological study. South African Med. J., 47:1025.
16. Eckstein, H.B. (1961) Endemic urinary lithiasis in Turkish children a clinical study of 119 .cases. Arch. Dis. Child., 36: 137.
17. Elliott, J.P. Jr., Gordon, J.O., Evans, J.W. and Platt, L. (1975) A stone season; a 10year retrospective study of 768 surgical stone cases with respect to seasonal variation. J. Urol., 114: 574.
18. Finlayson, B. Where and how does urinary stone disease start? An essay on the expectation on free-and fixed-particle urinary stone disease, in idiopathic urinary bladder stone disease. Sponsored by John E. Fogarty International Center. Edited by Robert Van Reen. Washington, DHEW Publication. 1977, p.7.
19. Fujita, K. (1979) Weather and the incidence of urinary stone colic. J. Urol., 121: 318.
20. Gaches, C.G.C., Gordon, I.R.S., Shore, D.F. and Roberts, J.B.M. (1975) Urinary lithiasis in childhood in the Bristol clinical area. Br. J. Urol., 47: 109.
21. Gharib, R. (1970) Lithiasis in the urinary tract of children. Chin. Pediatr., 9: 157.
22. Ghazali, S., Barratt, T.M. and Williams, D.I. (1973) Childhood urolithiasis in Britain. Arch. Dis. Child., 48: 291.
23. Halim, A., Vaezzadeh, K. and Makarem, E. Natural history of renal stone in Iranian children, in urinary calculus; international urinary stone conference. Edited J. Gwynne Brockis and Birdwell Finlayson. Littleton, PSG Publishing, 1981, p. 71.
24. Haistead, S.B. Studies on the epidemiology of idiopathic bladder stone disease, in idiopathic urinary bladder stone disease. Sponsored by John F. Fogarty International Center. Edited by Robert Van Reen. Washington, DHEW Publication, 1977, P. 121.
25. Halstead, S.B. and Valyasevi, A. (1967) Studies of bladder stone disease in Thialand. II. Epidemiologic studies in Ubol province. Am. J. Chin. Nutr., 20: 1329.
26. Illahi, M.A. (1967) Urinary calculi - their incidence and distribution in the urinary tract. Medicus, 34 : 149.
27. flan, F.A. Idiopathic bladder stones in Pakistan; a clinical study of 124 patients, in idiopathic urinary bladder stone disease, Sponsored by John E. Fogarty International Center. Edited by Robert Van Reen. Washington, DHEW Publication, 1977, p. 187.
28. Loutfi, A.H. Vesical lithiasis; etiology and management, in idiopathic urinary bladder stone disease. Sponsored by John E. Fogurty International Center. Edited by Robert Van Reen. Washington, DHEW Publication, 1977, p. 335.
29. Loutfi, A.H. and Abdel-Hamid, G. Research report on idiopathic urinary bladder stone disease in Egypt. Sponsored by John E. Fogarty International Center. Edited by Robert Van Reen. DHEW Publication, 1977, p.l77.
30. Loutfi, A.H., Van Reen, R. and Abdel-Hamid, G. (1974) Studies on bladder stone disease in Egyptian children.II. Methodology and general aspects of the disease. J. Egypt. Med. Assoc., 57 : 96.
31. Malek, R.S. Urolithiasis, in clinical pediatric urology. Edited by Panayotis P. Kelalis et al. Philadelphia, Saunders, 1976, v.2, p. 865.
32. Malek, R.S. and Kelalis, P. (1975) Pediatric nephrohithiasis. J. Urol., 113:545.
33. McCarrison, R. (1931) The causation of stone in India. Br. Med. J., 1:1009.
34. Mclaren, D.S. (1963) Nutritional factors in urinary lithiasis. East African Med. J., 40:178.
35. Myers, N.A.A. (1957) Urolithiasis in childhood. Arch. Dis. Child., 32:48.
36. Noronaha, R.F.X., Gregory, J.G. and Duke, J.J. (1979)
37. Urolithiasis in children. J. UroL, 121 : 478.
38. Prince, C.L. and Scardino, P.L. (1960) A statistical analysis of ureteral calculi. J. Urol., 83:561.
39. Puga, F., Paredes, S., Maguire, H., Morey, A., Izzo, C. and Kumsack, H. (1977) Urinary lithiasis in children. Ann. Nestle, 38:70.
40. Ralunan, M.A. and Van Reen, R. Studies on urinary bladder stone disease in Pakistani children, in urinary calculus; international urinary stone conference. Edited by J. Gwynne Brockis and Birdwell Finlayson. Littleton, PSG Publishing, 1981, P. 205.
41. Remzi, D., Cakmak, F. and Erkan, I. (1980) A study on the urolithiasis incidence in Turkish school-age children. J.Urol., 123:608.
42. Rizvi, S.A. (1975) Calculous disease; a survey of 400 patients. JPMA., 25:268.
43. Sadie, M. and Ziai, M. Urinary calculi in ban; urolithiasis in childhood, in idiopathic urinary bladder stone disease. Sponsored by John E. Fogarty International Center. Edited by Robert Van Reen. Washington, DHEW Publication, 1977, p. 199.
44. Sadre, M., Bastanfar, M. and Ziai, M. (1973) Urinary calculi in Iran; hospital experience over 93 years period with special reference to bladder stones in children. Trans R. Soc. Trop. Med. Hyg., 67:374.
45. Sastroamidjoju, S. Incidence of urinary calculi at the puskesmas (health center) kecamatan (district) cengkareng, Indonesia, in 1975, idiopathic urinary bladder stone disease. Sponsored by John E. Fogarty International Center. Edited by Robert Van Reen. Washington, DHEW Publication, 1977, p. 173.
46. Scott, R., Freeland, R., Mowat, W., Paterson, P.J., Orr, P.S., Yates, A.J. and Mills, E.A. The prevalence of renal stones in a random population and volunteer population, in urinary calculus; international urinary stone conference. Edited by J. Gwynne Brockis and Birdwell Finlayson. Littleton, PSG Publishing, 1981, p. 65.
47. Shahjehan, S. and Rahman, M.A. (1971) Studies on the etiology of urolithiasis in Karachi. Am. J. Clin. Nutr., 24:32.
48. Singh, J., Phogal, AC. and Singh, W. (1968) Bladder stone in children; comparative results of cystolithotomy with and without drainage. Br. J. Urol., 40 :472. Singh, F.P., Singh, L.B.K., Prasad, S.N. and Singh, M.G. (1978) Urolithiasis in Maninpur (North eastern region of India) incidence and chemical composition of stones. Am. J. Clin. Nutr., 31:1519.
49. Singh, S.M. Idiopathic urinary bladder stone disease in India; historical aspects, geographical incidence, and clinical features, in idiopathic urinary bladder stone disease. Sponsored by John E. Fogarty International Center. Edited by Robert Van Reen. Washington, DHEW Publication, 1977, p. 209.
50. Sutor, D.J. Stones; epidemiology and composition, in urology; tutorials in postgraduate medicine. Edited by G.D. Chisholm. London, Heinemann, 1980, P. 95.
51. Taneja, O.P., Mall, M.P. and Mittal, K.P. (1970) Urological aspects of endemic bladder stones in children. Aust. N.Z. J. Surg., 40: 130.
52. Teotia, M. and Teotia, S.P. (1977) Kidney and bladder stones in India. Postgrad. Med. J., 53 : 41.
53. Thalut, K., Rizal, A., Brockis, J.G., Bowyer, R.C., Taylor, T.A. and Wisniewski, Z.W. (1976) The endemic bladder stones of Indonesia; epidemiology and clinical features. Br. J. Urol., 48:6 17..
54. Thalut, K., Soemanto, Rizal, A., Brockis, J.G., Wisniewski, Z.S. and Taylor, T.A. Epidemiology of bladder stones in West Sumatra, in urinary calculus; international urinary stone conference. Edited by J. Gwynne Brockis and Birdwell Finlayson. Littleton, PSG Publishing, 1981, p. 195.
55. Valyasevi, A. and Van Reen, R. (1968) Pediatric bladder stone disease; current status of research. J. Pediatr., 72:546.
56. Van Reen, R. Geographical and nutritional aspects of endemic stones, in urinary calculus international urinary stone conference. Edited by J. Gwynne Brockis and Birdwell Finlayson. Littleton, PSG Publishing, 1981, p.177.
57. Wooton, I.D.P. Microanalysis in medical biochemistry, by Earal J. King, 5th ed. Edinburgh, Churchill Living-stone, 1974.
58. Williams, B. (1978) Regional variations in the incidence of urinary stones. Br. Med. J., 1:233.
59. Varley, H. Practical Clinical biochemistry 4th ed. New York, Inter Science, 1969.
60. Yelloly, J. (1829) Remarks on the tendency to calculus disease; with observations on the nature of urinary concretions and an analysis of a large part of the collection belonging to the Norfolk and Norwich Hospital. Phil. Trans. R. Soc., 119:55.

Journal of the Pakistan Medical Association has agreed to receive and publish manuscripts in accordance with the principles of the following committees: