renal biopsy and amyloid disease

1
967 1. Heptinstall, R. H., Joekes, A. M. Ann. rheum. Dis. 1960, 19, 126. 2. Werther, J. L., Schapira, A., Rubinstein, O., Janowitz, H. D. Amer. J. Med. 1960, 29, 416. with each other and with people in public health. " Surely the senior physicians and surgeons of our general hospitals are the persons to take the lead in forming such a partner- ship, each for its own community. Regular meetings of representatives of the three divisions of the National Health Service, and perhaps of the clergy also, in the area would soon show how each can best help the others and how the hospital and local-authority services can utilise the peculiar experiences of family doctors to supplement their own restricted and specialised training." RENAL BIOPSY AND AMYLOID DISEASE IMPORTANT points about renal amyloid disease are underlined by Heptinstall and Joekes 1 in an account of 11 cases proved by renal biopsy. These cases were found in a series of 220 biopsies; and Heptinstall and Joekes question the prevalent belief that amyloid disease is now rare. There was a history of osteomyelitis in 5, of pul- monary tuberculosis in 2, of chronic bronchiectasis in 2, and of rheumatoid arthritis in 1, leaving only 1 in which a presumptive diagnosis of primary amyloidosis was made. In the 2 cases of bronchiectasis and the case of rheumatoid arthritis, the primary disease had persisted and was active when the amyloid developed. In the 2 tuberculous cases there had been no activity for three and ten years. Of the 5 osteomyelitis cases 1 had been active up to a few months before the renal amyloidosis was proved, but in the other 4 there had been no evidence of activity for eight to forty years: 1 patient, with an interval of twenty- five years, had had ulcerative colitis for two years up to a year before the renal biopsy. (Does this suggest that amyloid may complicate ulcerative colitis ? Evidence of such an association is sparse; but Werther et al. have collected reports of 6 cases and also record an unex- pectedly high incidence in regional enteritis.) The patient with the forty-year interval had been admitted to hos- pital several times on account of minor illnesses, but proteinuria had not been found until some months before the renal biopsy. Heptinstall and Joekes remark that the apparent absence of proteinuria in some cases for a long time after the underlying lesions had become inactive cannot be taken as evidence against renal amyloid infil- tration in this interval; possibly, once started, amyloid deposition progresses very slowly in some cases and much more rapidly in others. Though in all cases proteinuria was found at the time of biopsy, only 4 patients had had oedema at any time, and in only 2 was this more than slight; none had been present in 2 patients with proteinuria for eight and three years. 2 patients had a much-reduced serum-albumin level, and in only 1 was the plasma-cholesterol over 300 mg. per 100 ml. On the other hand, hypertension was much commoner than in previous series: of the 11 patients, 7 had systolic blood-pressures of 150 or more mm. Hg. Heptinstall and Joekes suggest this may be due to their patients’ relatively good general condition; for in previous series the patients commonly had long- standing infection. Perhaps the most important finding was the good renal function despite the severe infiltration of the kidney, especially the glomeruli, with amyloid. In 9 of the 11 cases, every glomerulus in the biopsy specimen contained amyloid in the capillary tufts: even where the glomerular involvement was extensive the tubules were sometimes 3. Symmers, W. St. C. J. clin. Path. 1956, 9, 187 4. Lancet, 1958, i, 1378. not grossly abnormal, but in 3 cases tubular damage was also severe. In 1 of these renal function was so good as to cast doubt on the validity of the renal biopsy as repre- senting the total renal damage; but in this case three different pieces of kidney were taken at the same time and all showed the same changes. Other tests for amyloid, such as the congo-red and gum and liver biopsies, were negative in several of the cases after the onset of pro- teinuria ; and thus renal biopsy emerges as the most certain method of making the diagnosis when the full nephrotic syndrome is not present. Amyloid disease is a mimic 3 with many vagaries 4; and its insidiousness is again shown by this series. THE DEVELOPING CHILD ALTHOUGH there is now reliable information on the results of cross-sectional and serial studies of child popula- tions, regrettably little is known about the important variables in the development of the individual child. For the study of process rather than product, longitudinal investigations of individual children are required; and Prof. Herbert Birch, in a lecture at the Maudsley Hospital on Oct. 12, described some of the findings of his current work at the Albert Einstein College of Medicine, New York. The clash of views between genetecists and environ- mentalists is, he believes, being replaced by a more fruitful interest in the interaction between the biological substratum and environmental influence. He has studied the behavioural characteristics of 105 infants, mostly of middle-class, college-educated Americans-a socially homogeneous group being deliberately chosen for the better study of organismic variability. Information was sought on the child’s behaviour in natural surroundings: rather than from laboratory tests. Two independent trained observers each spent a day in the household, and their reports were compared with each other and also with that from the parents. There was significant agreement between the two trained observers but still greater agree- ment between the separate observers and the parents. Thus, provided attention was confined to actual behaviour described and parental interpretations of this were ignored, the parents’ reports were valid and reliable. From this information nine separate characteristics of behaviour could be identified in each child: activity level, rhythmicity of function or its absence, response to new stimuli (whether an " approacher " or " withdrawer "), adapta- bility, intensity of adaptable pattern reaction, threshold of responsiveness, quality of mood, distractability, and atten- tion span and persistence. Comparison of item analysis with protocol analysis showed that there was negligible " halo " effect in these assessments. Although they varied greatly from child to child, and at different ages related to different basic contents of activities, the formal characteristics remained remark- ably constant in each individual child; and after two years some 90% of the children retained their original position on a three-point scale (with an 001 level of reliability). This remarkable stability of behaviour seems to persist even after five years, but fewer children have been studied for this period. The effects on these characteristics of different stresses, such as parental death or separation or birth of sibs, have been studied as they occurred. Rather surprisingly, little effect was found; and, although the form of activity may

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Page 1: RENAL BIOPSY AND AMYLOID DISEASE

967

1. Heptinstall, R. H., Joekes, A. M. Ann. rheum. Dis. 1960, 19, 126.2. Werther, J. L., Schapira, A., Rubinstein, O., Janowitz, H. D. Amer. J.

Med. 1960, 29, 416.

with each other and with people in public health. " Surelythe senior physicians and surgeons of our general hospitalsare the persons to take the lead in forming such a partner-ship, each for its own community. Regular meetings ofrepresentatives of the three divisions of the National

Health Service, and perhaps of the clergy also, in the areawould soon show how each can best help the others andhow the hospital and local-authority services can utilisethe peculiar experiences of family doctors to supplementtheir own restricted and specialised training."

RENAL BIOPSY AND AMYLOID DISEASE

IMPORTANT points about renal amyloid disease are

underlined by Heptinstall and Joekes 1 in an account of11 cases proved by renal biopsy. These cases were foundin a series of 220 biopsies; and Heptinstall and Joekesquestion the prevalent belief that amyloid disease is nowrare. There was a history of osteomyelitis in 5, of pul-monary tuberculosis in 2, of chronic bronchiectasis in 2,and of rheumatoid arthritis in 1, leaving only 1 in which apresumptive diagnosis of primary amyloidosis was made.In the 2 cases of bronchiectasis and the case of rheumatoidarthritis, the primary disease had persisted and was

active when the amyloid developed. In the 2 tuberculouscases there had been no activity for three and ten years.Of the 5 osteomyelitis cases 1 had been active up to a fewmonths before the renal amyloidosis was proved, but inthe other 4 there had been no evidence of activity foreight to forty years: 1 patient, with an interval of twenty-five years, had had ulcerative colitis for two years up to a

year before the renal biopsy. (Does this suggest thatamyloid may complicate ulcerative colitis ? Evidence ofsuch an association is sparse; but Werther et al. havecollected reports of 6 cases and also record an unex-

pectedly high incidence in regional enteritis.) The patientwith the forty-year interval had been admitted to hos-pital several times on account of minor illnesses, butproteinuria had not been found until some months beforethe renal biopsy. Heptinstall and Joekes remark that theapparent absence of proteinuria in some cases for a longtime after the underlying lesions had become inactivecannot be taken as evidence against renal amyloid infil-tration in this interval; possibly, once started, amyloiddeposition progresses very slowly in some cases and muchmore rapidly in others.Though in all cases proteinuria was found at the time

of biopsy, only 4 patients had had oedema at any time,and in only 2 was this more than slight; none had beenpresent in 2 patients with proteinuria for eight and threeyears. 2 patients had a much-reduced serum-albuminlevel, and in only 1 was the plasma-cholesterol over300 mg. per 100 ml. On the other hand, hypertensionwas much commoner than in previous series: of the 11patients, 7 had systolic blood-pressures of 150 or moremm. Hg. Heptinstall and Joekes suggest this may be dueto their patients’ relatively good general condition; forin previous series the patients commonly had long-standing infection.Perhaps the most important finding was the good renal

function despite the severe infiltration of the kidney,especially the glomeruli, with amyloid. In 9 of the 11cases, every glomerulus in the biopsy specimen containedamyloid in the capillary tufts: even where the glomerularinvolvement was extensive the tubules were sometimes

3. Symmers, W. St. C. J. clin. Path. 1956, 9, 1874. Lancet, 1958, i, 1378.

not grossly abnormal, but in 3 cases tubular damage wasalso severe. In 1 of these renal function was so good asto cast doubt on the validity of the renal biopsy as repre-senting the total renal damage; but in this case threedifferent pieces of kidney were taken at the same timeand all showed the same changes. Other tests for amyloid,such as the congo-red and gum and liver biopsies, werenegative in several of the cases after the onset of pro-teinuria ; and thus renal biopsy emerges as the mostcertain method of making the diagnosis when the full

nephrotic syndrome is not present.Amyloid disease is a mimic 3 with many vagaries 4; and

its insidiousness is again shown by this series.

THE DEVELOPING CHILD

ALTHOUGH there is now reliable information on theresults of cross-sectional and serial studies of child popula-tions, regrettably little is known about the importantvariables in the development of the individual child. Forthe study of process rather than product, longitudinalinvestigations of individual children are required; andProf. Herbert Birch, in a lecture at the Maudsley Hospitalon Oct. 12, described some of the findings of his currentwork at the Albert Einstein College of Medicine, New York.The clash of views between genetecists and environ-

mentalists is, he believes, being replaced by a more

fruitful interest in the interaction between the biologicalsubstratum and environmental influence. He has studiedthe behavioural characteristics of 105 infants, mostly ofmiddle-class, college-educated Americans-a sociallyhomogeneous group being deliberately chosen for thebetter study of organismic variability. Information was

sought on the child’s behaviour in natural surroundings:rather than from laboratory tests. Two independenttrained observers each spent a day in the household, andtheir reports were compared with each other and also withthat from the parents. There was significant agreementbetween the two trained observers but still greater agree-ment between the separate observers and the parents.Thus, provided attention was confined to actual behaviourdescribed and parental interpretations of this were ignored,the parents’ reports were valid and reliable. From thisinformation nine separate characteristics of behaviourcould be identified in each child: activity level, rhythmicityof function or its absence, response to new stimuli

(whether an "

approacher " or " withdrawer "), adapta-bility, intensity of adaptable pattern reaction, threshold ofresponsiveness, quality of mood, distractability, and atten-tion span and persistence. Comparison of item analysiswith protocol analysis showed that there was negligible" halo " effect in these assessments.

Although they varied greatly from child to child, andat different ages related to different basic contents of

activities, the formal characteristics remained remark-

ably constant in each individual child; and after two

years some 90% of the children retained their originalposition on a three-point scale (with an 001 level of

reliability). This remarkable stability of behaviour seemsto persist even after five years, but fewer children havebeen studied for this period.The effects on these characteristics of different stresses,

such as parental death or separation or birth of sibs, havebeen studied as they occurred. Rather surprisingly, littleeffect was found; and, although the form of activity may