134 The basic Lord procedure was modified in thirteen of the patients by deliberate excision and immediate suture of prolapsing tissue. It was thought that in the same circumstances Lord would have treated such patients by clamping and excision of redundant tissue using his special
a difficult nursing problem preoperatively because of mental deterioration and was virtually incontinent of urine. The only reason for doing the operation was the complication of irreducibility, and this certainly was cured by the procedure.
clamp. The only painful time of the operation is that up till the removal of the foam pack. Subsequent to its removal only a very occasional dose of analgesic agent is needed. Patients are usually discharged on the second postoperative
day. Results Of the fifty patients two died of coronary-artery disease eighteen months and twenty-six months after operation; at the last follow-up before their death they were symptom-free and showed no evidence of hasmorrhoidal disease. Forty-eight patients have been followed up for four or more years; the longest follow-up is six years. Of these, thirty-six patients are symptom-free and have no complaints. Examination of these thirty-six patients shows that in nineteen there is still evidence of anal congestion but no distinct haemorrhoids. Of the remaining twelve patients, four have undergone a standard St. Mark’s type operation for persistent prolapse and bleeding. Four of the remaining eight have intermittent bleeding only when they become constipated; they state that this is considerably less than before the operation, and they have not elected to have any further treatment either by local injection The remaining four are symptom-free or operation. but on examination they have prolapsing haemorrhoidal tissue and their result is considered unsatisfactory. In reviewing the various stages of follow-up in these patients, it was seen that, of the twelve patients with an unsatisfactory result, seven already had symptoms or signs of returning disease at the twelve months’ follow-up and all twelve showed evidence of disease by eighteen months. It seems that the results at eighteen months will be the same as at four years, but that follow-up periods of less than a year are unsatis-
factory. Complications The complication which worries most surgeons is the induction of incontinence. Twenty out of the fifty patients had mild incontinence for four to twentysix days postoperatively. This incontinence was for flatus and mucus but there was no lack of control of fasces. However, there were two patients, not in this series, whom I had treated by the Lord method and who have claimed to have become incontinent after the operation. One patient, three months after dilatation, began to pass large quantities of blood-stained mucus intermittently, associated with diarrhcea.
This
was
by his general practitioner and However, sigmoidoscopy revealed
a a
termed incontinence consultant surgeon. very acute ulcerative
colitis and this was confirmed both by histological examination and by barium-enema studies. His ulcerative colitis is progressing, and he will require colectomy. The other patient apparently rendered incontinent by the operation was an elderly man who was treated by the Lord method rather than conventional heemorrhoidectomy for large, prolapsing irreducible hxmorrhoids. He had been
Discussion It would appear from this admittedly small series that the method of treatment advocated by Lord is successful in 75 % of patients. The same can be said of rubber-band ligation. Both methods have obvious advantages over more conventional hsemorrhoidectomy, particularly in freedom from operative and postand much shorter stay in hospital. in the series herein reported have used the Lord type dilator, and took normacol in sufficient
operative pain All patients
to produce one or two soft bulky bowel motions per day. However, as time has gone by I have shortened the period of use of the dilator and over the past year have abandoned its use completely. This change does not seem to have influenced results. amounts
REFERENCES 1. 2.
3. 4. 5. 6. 7. 8.
Lord, P. H. Proc. R. Soc. Med. 1968, 61, 935. Lord, P. H. Prog. Surg. 1972, 10, 109. MacIntyre, I. M. C., Balfour, T. W. Lancet, 1972, i, 1094. Georgoulis, B. Dis. Colon Rectum, 1971, 14, 147. Hood, T. R., Williams, J. A. Am. J. Surg. 1971, 122, 545. Bennett, R. C., Friedman, M. H., Goligher, J. C. Br. med. J. 1963, ii, 216. Levitt, S. Proceedings of the 46th General Scientific Meeting of the Royal Australasian College of Surgeons, 1973, p. 583. Cormie, J., McNair, T. J. Scott. med. J. 1959, 4, 571.
URINARY-TRACT INFECTION: LOCALISATION AND VIRULENCE OF ESCHERICHIA COLI G. M. KALMANSON M. TURCK
H. J. HARWICK L. B. GUZE
Medical and Research Services, Wadsworth V. A. Hospital, Los Angeles, Harbor Hospital, Torrance, and Harborview Medical Center, Seattle, Washington, U.S.A.
Virulence of 15 strains of Escherichia coli from the human upper urinary tract was compared with that of 16 strains from the lower urinary tract, using an ascending infection in the mouse. No significant difference was found. There was no significant difference in frequency of K antigen and ability to ferment dulcitol between 32 lower strains and 31 upper strains. However, 22 strains containing K antigen, regardless of anatomical site of localisation, were more significantly likely to cause infection than 9 strains with no antigen. Similarly, 23 dulcitolfermenting strains, regardless of site of localisation, were significantly more likely to cause infection than
Sum ary
8
non-fermenting
strains.
Introduction LOCALISATION of the site of infection to the upper or lower genitourinary tract by clinical methods alone is often difficult. For this reason, a variety of other approaches have been used, including separate culture
135
of bladder and renal urine. Stamey et al 1 described a technique whereby the bladder urine is first cultured, the bladder is then washed, and ureteral catheters are inserted to sample urine from the upper urinary tract. The question then arises whether bacteria from the kidney are more virulent than those confined to the bladder or whether host factors have the major role in determining whether bacteria will infect the upper urinary tract. We have investigated whether upperurinary-tract isolates are more virulent than those from the lower urinary tract alone. The experimental model of virulence we used was an ascending infection with Escherichia coli in diuresed mice. This was originally described by Keane and Freedman2 and was extended TABLE I-RELATION OF SITE OF ORIGIN OF E. COLI AND VIRULENCE FOR THE MOUSE
Log number bacteria per gramme kidney tissue and number of kidneys from which data derived in parentheses. t Number of kidneys infected (any E. coli present)/number examined.
by us.’3 We found
that possession of K antigen and fermentation of dulcitol correlated with mouse virulence judged by renal microbial population and proportion of kidneys that became infected. We report here a study of 31 strains of E. coli-16 from lower and 15 from upper urinary-tract infection-for virulence in mice. These and an additional 32 strains were studied for (1) possession of K antigen, and (2) fermentation of dulcitol.
TABLE II-PRESENCE OF K ANTIGEN AND FERMENTATION OF DULCITOL IN STRAINS OF E. COLI DERIVED FROM UPPER AND LOWER URINARYTRACT INFECTIONS
16 from the lower tract were studied. Data are shown in table i. Renal microbial population is shown as log per gramme kidney tissue. The numbers in parentheses are the numbers of kidneys from which data were derived. Proportion of infected kidneys is shown as a fraction, the numerator representing infected kidneys, the denominator total number of kidneys examined. The results demonstrate clearly that there was no relation between site of origin and virulence for the mouse. Neither the log number of renal bacteria nor the proportion of infected kidneys differed when mice were infected with upper or lower strains. Relation ofK Antigen and Dulcitol Fermentation to Site of Origin All 63 strains were studied for presence of K antigen and dulcitol fermentation. Table 11 compares findings for K antigen, dulcitol fermentation, and both together in 31 upper versus 32 lower urinary-tract isolates. No significant differences were found.
Presence ofK Antigen and Virulence for Mouse Data concerning the relation of virulence to K antigen are presented in table in. It can be seen that, if renal microbial population including all kidneys and TABLE III-RELATION OF K ANTIGEN IN E. COLI AND VIRULENCE FOR THE MOUSE
Materials and Methods Strains of E. coli
were isolated from 63 women with well-documented recurrent infections of the urinary tract. The site of infection was established by bilateral ureteral catheterisation employing methods described previously.4 31 strains were from the upper urinary tract, and 32 from the lower urinary tract. The method of cultivation of bacteria, media used, production of ascending pyelonephritis in mice diuresed by ingestion of 5% glucose as sole fluid source, and determination of renal microbial population have been described.5 Mice were killed 2 weeks after infection. Presence of K antigen was determined by the method of Glynn.6 K antigen was measured
four times in each of the 63 strains to demonstrate its Dulcitol was presence at a confidence level of 0’05. fermented in phenol-red broth base (Difco) with 1% dulcitol added. Final readings were at 72 hours.
*
Log number bacteria per gramme kidney tissue and number of kidneys from which data derived in parentheses. t Number of kidneys infected (any E. coli present)/number examined. TABLE IV-RELATION OF FERMENTATION OF DULCITOL BY E. COLI AND VIRULENCE FOR THE MOUSE
Results Relation
ofVirulence for Mouse to Site ofOrigin Relationship of site of origin to virulence for
the evaluated in three ways: renal microbial population, including all kidneys; including only infected kidneys (a kidney with any number of E. coli was considered infected); and proportion of kidneys infected. 15 strains from the upper urinary tract and
mouse was
*
Log number bacteria
per gramme kidney tissue and number of kidneys from which data derived. t Number of kidneys infected (any E. coli present)/number examined.
136
proportion of infected kidneys are compared, strains possessing K antigen are significantly more virulent than those without K antigen. If only infected kidneys are considered, there is no significant difference in renal microbial population. the
Fermentation of Dulcitol and Virulence for Mouse Virulence of dulcitol fermenting and non-fermenting strains is compared in table iv. Dulcitol-fermenting strains were significantly more virulent than nonfermenting strains as judged by renal microbial population, all kidneys included and proportion of infected kidneys. When infected kidneys only are considered, no difference in renal microbial population is found. Discussion has shown that strains of B. coli isolated
This study from the upper urinary tract are not significantly more virulent for the mouse, as determined by production of a retrograde pyelonephritis, than strains isolated from the bladder. It is of course possible that this does not correspond to virulence in man. However, no other approach is available currently. Anatomical localisation studies only demonstrate presence of bacteria in the upper urinary tract. Exactly where the bacteria are may vary. They may be in the parenchyma or the pelvic urothelium, or they may only be growing in pelvic urine. To diagnose pyelonephritis, presence of bacteria in the upper urinary tract is not sufficient: some evidence of kidney damage must be demonstrated. Decrease in urinary concentrating ability may be an early sign of such damage.7 Circulating antibody against B. coli generally correlates with parenchymal disease, but may not be helpful in an individual patient 8 Furthermore, it has been shown that putting bacteria in a bladder pouch can lead to antibody production without any possibility of renal
invasion.9 In this study, incidence of K antigen was no different between upper and lower tract isolates. This is contrary to the results of Glynn et al.6 However, animal virulence was positively related to presence of K antigen as was reported before 3 The data in mice suggest that K-antigen-containing strains were significantly more likely to cause renal infection, but, once infection occurred, renal microbial population of K antigen positive and negative strains was not different. The present
study confirms and extends our previous
investigation, which demonstrated a correlation between ability to ferment dulcitol and mouse virulence.a Here also, as with K antigen, it was the likelihood of infection that was increased. Thus host factors, rather than intrinsic parasite virulence, may determine whether a strain of B. coli will establish itself in the upper urinary tract. It is probable that reflux plays a role. The ability to elicit and react to local antibody or other defence factors of the urothelium may be pertinent. Other, unknown host factors may determine localisation of the bacteria. This work 4830-01.
was
supported
in part by V.A.
project
no.
Requests for reprints should be addressed to L. B. G., 691/151, Veterans Administration Wadsworth Hospital Center,
Wilshire and Sawtelle Boulevards, Los
Angeles, California
90073, U.S.A. REFERENCES 1.
2. 3. 4.
5. 6. 7. 8. 9.
T.
A., Govan, D. E., Palmer, J. M. Medicine, Baltimore, Stamey, 1965, 44, 1. Keane, W. F., Freedman, L. R. Yale J. Biol. Med. 1967, 40, 231. Guze, L. B., Montgomerie, J. Z., Potter, C. S., Kalmanson, G. M. ibid. 1973, 46, 203. Turck, M., Ronald, A. R., Petersdorf, R. G. New Engl. J. Med. 1968, 278, 422. Kalmanson, G. M., Montgomerie, J. Z., Hubert, E. G., Barajas, L., Guze, L. B. Yale J. Biol. Med. 1973, 46, 196. Glynn, A. A., Brumfitt, W., Howard, C. J. Lancet, 1971, i, 514. Kleeman, C. R., Hewitt, W. L., Guze, L. B. Medicine, Baltimore, 1960, 39, 3. Clark, H., Ronald, A. R., Turck, M. J. infect. Dis. 1971, 123, 539. Agarwal, M. K., Darwish, M. E., Staubitz, W. J., Neter, E. Invest. Urol. 1970, 8, 153.
THE SMALL-INTESTINAL MUCOSA IN COW’S MILK ALLERGY
MARGOT SHINER
JANET BALLARD MARGUERITE E. SMITH Medical Research Council Gastroenterology Unit and Department of Pœdiatrics, Central Middlesex Hospital, Park Royal, London NW10 7NS Two infants investigated for allergy to cow’s milk proteins exhibited a local reaginic reaction in the small intestine after ingesting cow’s milk, as shown by increased mucosal IgE plasmacells and degranulation of mast cells. IgM plasma-cells and the staining of connective tissue and basement membranes with antisera to IgG and C3 complement were also increased, indicating several simultaneous immune reactions in the intestinal mucosa. These findings may provide a sound basis for diagnosis of such an allergy and for the treatment of similar patients with disodium cromoglycate. Sum ary
Introduction ALTHOUGH allergy to cow’s milk proteins in infancy is well recognised,l2 it may be difficult to diagnose. In acute cases symptoms appear shortly after exposure to cow’s milk and are characterised by vomiting and diarrhoea.- Chronic ill health and failure to thrive may also be the presenting symptoms of a less acute intolerance in infancy. Hitherto the diagnosis has been suspected in patients with an appropriate history and indications such. as eosinophilia and occult blood in the stools. Improvement of symptoms generally follows the exclusion of cow’s milk protein from the feeds, and reintroduction of the cow’s milk often leads
relapses. high titres of serum-antibodies to cow’s milk protein in affected infants suggest a leakage of protein through the intestinal mucosal barrier, and the eosinophilia indicates that a reaginic immune response is involved in the pathogenesis of this .condition. Activation of serum-complement shortly after milk challenge has been reported3 indicates that more than one type to severe
The
of immune response is involved. The small-intestinal mucosa is probably the primary seat of a reaginic reaction after ingestion of cow’s milk, but nothing is known about the sequence or the nature of such a reaction.
a difficult nursing problem preoperatively because of mental deterioration and was virtually incontinent of urine. The only reason for doing the operation was the complication of irreducibility, and this certainly was cured by the procedure.
clamp. The only painful time of the operation is that up till the removal of the foam pack. Subsequent to its removal only a very occasional dose of analgesic agent is needed. Patients are usually discharged on the second postoperative
day. Results Of the fifty patients two died of coronary-artery disease eighteen months and twenty-six months after operation; at the last follow-up before their death they were symptom-free and showed no evidence of hasmorrhoidal disease. Forty-eight patients have been followed up for four or more years; the longest follow-up is six years. Of these, thirty-six patients are symptom-free and have no complaints. Examination of these thirty-six patients shows that in nineteen there is still evidence of anal congestion but no distinct haemorrhoids. Of the remaining twelve patients, four have undergone a standard St. Mark’s type operation for persistent prolapse and bleeding. Four of the remaining eight have intermittent bleeding only when they become constipated; they state that this is considerably less than before the operation, and they have not elected to have any further treatment either by local injection The remaining four are symptom-free or operation. but on examination they have prolapsing haemorrhoidal tissue and their result is considered unsatisfactory. In reviewing the various stages of follow-up in these patients, it was seen that, of the twelve patients with an unsatisfactory result, seven already had symptoms or signs of returning disease at the twelve months’ follow-up and all twelve showed evidence of disease by eighteen months. It seems that the results at eighteen months will be the same as at four years, but that follow-up periods of less than a year are unsatis-
factory. Complications The complication which worries most surgeons is the induction of incontinence. Twenty out of the fifty patients had mild incontinence for four to twentysix days postoperatively. This incontinence was for flatus and mucus but there was no lack of control of fasces. However, there were two patients, not in this series, whom I had treated by the Lord method and who have claimed to have become incontinent after the operation. One patient, three months after dilatation, began to pass large quantities of blood-stained mucus intermittently, associated with diarrhcea.
This
was
by his general practitioner and However, sigmoidoscopy revealed
a a
termed incontinence consultant surgeon. very acute ulcerative
colitis and this was confirmed both by histological examination and by barium-enema studies. His ulcerative colitis is progressing, and he will require colectomy. The other patient apparently rendered incontinent by the operation was an elderly man who was treated by the Lord method rather than conventional heemorrhoidectomy for large, prolapsing irreducible hxmorrhoids. He had been
Discussion It would appear from this admittedly small series that the method of treatment advocated by Lord is successful in 75 % of patients. The same can be said of rubber-band ligation. Both methods have obvious advantages over more conventional hsemorrhoidectomy, particularly in freedom from operative and postand much shorter stay in hospital. in the series herein reported have used the Lord type dilator, and took normacol in sufficient
operative pain All patients
to produce one or two soft bulky bowel motions per day. However, as time has gone by I have shortened the period of use of the dilator and over the past year have abandoned its use completely. This change does not seem to have influenced results. amounts
REFERENCES 1. 2.
3. 4. 5. 6. 7. 8.
Lord, P. H. Proc. R. Soc. Med. 1968, 61, 935. Lord, P. H. Prog. Surg. 1972, 10, 109. MacIntyre, I. M. C., Balfour, T. W. Lancet, 1972, i, 1094. Georgoulis, B. Dis. Colon Rectum, 1971, 14, 147. Hood, T. R., Williams, J. A. Am. J. Surg. 1971, 122, 545. Bennett, R. C., Friedman, M. H., Goligher, J. C. Br. med. J. 1963, ii, 216. Levitt, S. Proceedings of the 46th General Scientific Meeting of the Royal Australasian College of Surgeons, 1973, p. 583. Cormie, J., McNair, T. J. Scott. med. J. 1959, 4, 571.
URINARY-TRACT INFECTION: LOCALISATION AND VIRULENCE OF ESCHERICHIA COLI G. M. KALMANSON M. TURCK
H. J. HARWICK L. B. GUZE
Medical and Research Services, Wadsworth V. A. Hospital, Los Angeles, Harbor Hospital, Torrance, and Harborview Medical Center, Seattle, Washington, U.S.A.
Virulence of 15 strains of Escherichia coli from the human upper urinary tract was compared with that of 16 strains from the lower urinary tract, using an ascending infection in the mouse. No significant difference was found. There was no significant difference in frequency of K antigen and ability to ferment dulcitol between 32 lower strains and 31 upper strains. However, 22 strains containing K antigen, regardless of anatomical site of localisation, were more significantly likely to cause infection than 9 strains with no antigen. Similarly, 23 dulcitolfermenting strains, regardless of site of localisation, were significantly more likely to cause infection than
Sum ary
8
non-fermenting
strains.
Introduction LOCALISATION of the site of infection to the upper or lower genitourinary tract by clinical methods alone is often difficult. For this reason, a variety of other approaches have been used, including separate culture
135
of bladder and renal urine. Stamey et al 1 described a technique whereby the bladder urine is first cultured, the bladder is then washed, and ureteral catheters are inserted to sample urine from the upper urinary tract. The question then arises whether bacteria from the kidney are more virulent than those confined to the bladder or whether host factors have the major role in determining whether bacteria will infect the upper urinary tract. We have investigated whether upperurinary-tract isolates are more virulent than those from the lower urinary tract alone. The experimental model of virulence we used was an ascending infection with Escherichia coli in diuresed mice. This was originally described by Keane and Freedman2 and was extended TABLE I-RELATION OF SITE OF ORIGIN OF E. COLI AND VIRULENCE FOR THE MOUSE
Log number bacteria per gramme kidney tissue and number of kidneys from which data derived in parentheses. t Number of kidneys infected (any E. coli present)/number examined.
by us.’3 We found
that possession of K antigen and fermentation of dulcitol correlated with mouse virulence judged by renal microbial population and proportion of kidneys that became infected. We report here a study of 31 strains of E. coli-16 from lower and 15 from upper urinary-tract infection-for virulence in mice. These and an additional 32 strains were studied for (1) possession of K antigen, and (2) fermentation of dulcitol.
TABLE II-PRESENCE OF K ANTIGEN AND FERMENTATION OF DULCITOL IN STRAINS OF E. COLI DERIVED FROM UPPER AND LOWER URINARYTRACT INFECTIONS
16 from the lower tract were studied. Data are shown in table i. Renal microbial population is shown as log per gramme kidney tissue. The numbers in parentheses are the numbers of kidneys from which data were derived. Proportion of infected kidneys is shown as a fraction, the numerator representing infected kidneys, the denominator total number of kidneys examined. The results demonstrate clearly that there was no relation between site of origin and virulence for the mouse. Neither the log number of renal bacteria nor the proportion of infected kidneys differed when mice were infected with upper or lower strains. Relation ofK Antigen and Dulcitol Fermentation to Site of Origin All 63 strains were studied for presence of K antigen and dulcitol fermentation. Table 11 compares findings for K antigen, dulcitol fermentation, and both together in 31 upper versus 32 lower urinary-tract isolates. No significant differences were found.
Presence ofK Antigen and Virulence for Mouse Data concerning the relation of virulence to K antigen are presented in table in. It can be seen that, if renal microbial population including all kidneys and TABLE III-RELATION OF K ANTIGEN IN E. COLI AND VIRULENCE FOR THE MOUSE
Materials and Methods Strains of E. coli
were isolated from 63 women with well-documented recurrent infections of the urinary tract. The site of infection was established by bilateral ureteral catheterisation employing methods described previously.4 31 strains were from the upper urinary tract, and 32 from the lower urinary tract. The method of cultivation of bacteria, media used, production of ascending pyelonephritis in mice diuresed by ingestion of 5% glucose as sole fluid source, and determination of renal microbial population have been described.5 Mice were killed 2 weeks after infection. Presence of K antigen was determined by the method of Glynn.6 K antigen was measured
four times in each of the 63 strains to demonstrate its Dulcitol was presence at a confidence level of 0’05. fermented in phenol-red broth base (Difco) with 1% dulcitol added. Final readings were at 72 hours.
*
Log number bacteria per gramme kidney tissue and number of kidneys from which data derived in parentheses. t Number of kidneys infected (any E. coli present)/number examined. TABLE IV-RELATION OF FERMENTATION OF DULCITOL BY E. COLI AND VIRULENCE FOR THE MOUSE
Results Relation
ofVirulence for Mouse to Site ofOrigin Relationship of site of origin to virulence for
the evaluated in three ways: renal microbial population, including all kidneys; including only infected kidneys (a kidney with any number of E. coli was considered infected); and proportion of kidneys infected. 15 strains from the upper urinary tract and
mouse was
*
Log number bacteria
per gramme kidney tissue and number of kidneys from which data derived. t Number of kidneys infected (any E. coli present)/number examined.
136
proportion of infected kidneys are compared, strains possessing K antigen are significantly more virulent than those without K antigen. If only infected kidneys are considered, there is no significant difference in renal microbial population. the
Fermentation of Dulcitol and Virulence for Mouse Virulence of dulcitol fermenting and non-fermenting strains is compared in table iv. Dulcitol-fermenting strains were significantly more virulent than nonfermenting strains as judged by renal microbial population, all kidneys included and proportion of infected kidneys. When infected kidneys only are considered, no difference in renal microbial population is found. Discussion has shown that strains of B. coli isolated
This study from the upper urinary tract are not significantly more virulent for the mouse, as determined by production of a retrograde pyelonephritis, than strains isolated from the bladder. It is of course possible that this does not correspond to virulence in man. However, no other approach is available currently. Anatomical localisation studies only demonstrate presence of bacteria in the upper urinary tract. Exactly where the bacteria are may vary. They may be in the parenchyma or the pelvic urothelium, or they may only be growing in pelvic urine. To diagnose pyelonephritis, presence of bacteria in the upper urinary tract is not sufficient: some evidence of kidney damage must be demonstrated. Decrease in urinary concentrating ability may be an early sign of such damage.7 Circulating antibody against B. coli generally correlates with parenchymal disease, but may not be helpful in an individual patient 8 Furthermore, it has been shown that putting bacteria in a bladder pouch can lead to antibody production without any possibility of renal
invasion.9 In this study, incidence of K antigen was no different between upper and lower tract isolates. This is contrary to the results of Glynn et al.6 However, animal virulence was positively related to presence of K antigen as was reported before 3 The data in mice suggest that K-antigen-containing strains were significantly more likely to cause renal infection, but, once infection occurred, renal microbial population of K antigen positive and negative strains was not different. The present
study confirms and extends our previous
investigation, which demonstrated a correlation between ability to ferment dulcitol and mouse virulence.a Here also, as with K antigen, it was the likelihood of infection that was increased. Thus host factors, rather than intrinsic parasite virulence, may determine whether a strain of B. coli will establish itself in the upper urinary tract. It is probable that reflux plays a role. The ability to elicit and react to local antibody or other defence factors of the urothelium may be pertinent. Other, unknown host factors may determine localisation of the bacteria. This work 4830-01.
was
supported
in part by V.A.
project
no.
Requests for reprints should be addressed to L. B. G., 691/151, Veterans Administration Wadsworth Hospital Center,
Wilshire and Sawtelle Boulevards, Los
Angeles, California
90073, U.S.A. REFERENCES 1.
2. 3. 4.
5. 6. 7. 8. 9.
T.
A., Govan, D. E., Palmer, J. M. Medicine, Baltimore, Stamey, 1965, 44, 1. Keane, W. F., Freedman, L. R. Yale J. Biol. Med. 1967, 40, 231. Guze, L. B., Montgomerie, J. Z., Potter, C. S., Kalmanson, G. M. ibid. 1973, 46, 203. Turck, M., Ronald, A. R., Petersdorf, R. G. New Engl. J. Med. 1968, 278, 422. Kalmanson, G. M., Montgomerie, J. Z., Hubert, E. G., Barajas, L., Guze, L. B. Yale J. Biol. Med. 1973, 46, 196. Glynn, A. A., Brumfitt, W., Howard, C. J. Lancet, 1971, i, 514. Kleeman, C. R., Hewitt, W. L., Guze, L. B. Medicine, Baltimore, 1960, 39, 3. Clark, H., Ronald, A. R., Turck, M. J. infect. Dis. 1971, 123, 539. Agarwal, M. K., Darwish, M. E., Staubitz, W. J., Neter, E. Invest. Urol. 1970, 8, 153.
THE SMALL-INTESTINAL MUCOSA IN COW’S MILK ALLERGY
MARGOT SHINER
JANET BALLARD MARGUERITE E. SMITH Medical Research Council Gastroenterology Unit and Department of Pœdiatrics, Central Middlesex Hospital, Park Royal, London NW10 7NS Two infants investigated for allergy to cow’s milk proteins exhibited a local reaginic reaction in the small intestine after ingesting cow’s milk, as shown by increased mucosal IgE plasmacells and degranulation of mast cells. IgM plasma-cells and the staining of connective tissue and basement membranes with antisera to IgG and C3 complement were also increased, indicating several simultaneous immune reactions in the intestinal mucosa. These findings may provide a sound basis for diagnosis of such an allergy and for the treatment of similar patients with disodium cromoglycate. Sum ary
Introduction ALTHOUGH allergy to cow’s milk proteins in infancy is well recognised,l2 it may be difficult to diagnose. In acute cases symptoms appear shortly after exposure to cow’s milk and are characterised by vomiting and diarrhoea.- Chronic ill health and failure to thrive may also be the presenting symptoms of a less acute intolerance in infancy. Hitherto the diagnosis has been suspected in patients with an appropriate history and indications such. as eosinophilia and occult blood in the stools. Improvement of symptoms generally follows the exclusion of cow’s milk protein from the feeds, and reintroduction of the cow’s milk often leads
relapses. high titres of serum-antibodies to cow’s milk protein in affected infants suggest a leakage of protein through the intestinal mucosal barrier, and the eosinophilia indicates that a reaginic immune response is involved in the pathogenesis of this .condition. Activation of serum-complement shortly after milk challenge has been reported3 indicates that more than one type to severe
The
of immune response is involved. The small-intestinal mucosa is probably the primary seat of a reaginic reaction after ingestion of cow’s milk, but nothing is known about the sequence or the nature of such a reaction.
