1309 MULTIPLE SCLEROSIS AND VILLOUS ATROPHY
SIR,-In their report of
of malabsorption associated with multiple sclerosis Dr Fantelli and colleagues (May 13, p. 1039) describe villous atrophy in three separate jejunal-biopsy specimens and the entire small intestine at necropsy. With all this material available Fantelli et al. chose to illustrate their letter with a section of jejunal mucosa which has been cut transversely and is totally unsuitable for the assessment of villous architecture. While jejunal biopsy remains the central investigation in patients with malabsorption it is imperative that the biopsy be correctly oriented, fixed, and sectioned so that vertical sections of good quality are obtained. Incorrect orientation and sectioning can lead to artefactual subtotal villous atrophy when the mucosa is completely normal.’ Unless the illustrations show correctly oriented material one must treat reports of the multiplicity of conditions said to be associated with villous atrophy with scepticism.
P. ISAACSON
**This letter has been shown lows.-ED.L.
to
Dr
Fantelli, whose reply fol-
S:R,—The point raised by Dr Isaacson is an important one. must assume, however, that Isaacson is referring to tan-
We
gential sectioning sectioning, for the following reasons: (1) not many would conceive that the diagnosis of lesions compatible with malabsorption would be more difficult on a transverse section of intestine rather than a longitudinal one; (2) the importance of biopsy interpretation lies in the perpendicularity to the muscularis mucosa; and not whether it is transverse or longitudinal; (3) no mention of transverse sectioning is made in Perera’s excellent article,’ but he does deal in detail with tangential artifacts. The recognition of tangential artifacts is crucial in smallbowel biopsy interpretation since it is one of the main sources of misinterpretation. Perera describes several helpful hints for the recognition of tangential artifact. One common artifact produces multiple rows of circular acinar profiles which frequently have no muscularis mucosae present. Our photograph demonstrates at most, two rows of circular acini with an intact muscularis clearly present at the bottom of the photograph. If the specimen were tangential, one might expect either more rows of acini or the lack of muscularis. Our illustration demonstrated a narrow lamina propria. It is difficult to imagine tangential sectioning producing a narrowing of the lamina propria. In fact, Perera mentions expansion of the lamina propria as a product of tangential sectioning. A multilayered surface epithelium is also frequently seen in tangential sections (our photo has a monolayered surface). And finally, Perera describes a warning sign of tangential sectioning-namely, elliptical profiles of cross sectioned crypts. All acini are circular in our
not transverse
photo.
We chose a pre-mortem specimen obtained from our institution because of uniform handling, processing, and staining as well as the almost universal presence of superficial autolysis in post mortem specimens, that, while diagnostically suitable, is not aesthetically suitable for publication. Our illustration demonstrates surface epithelium, absent villi, intact muscularis mucosse, and a narrowed lamina propria with an intense round-cell infiltrate of lymphocytes and plasma cells. We considered these findings sufficient for the diagnosis of an intestinal lesion compatible with malabsorption (which our patient clearly had on clinical and chemical
grounds). Cleveland Clinic, Cleveland, Ohio 44106, U S.A.
1.
Perera, D. R., Weinstein,
ENTEROPATHOGENIC ESCHERICHIA COLI
a case
Department of Pathology, University of Southampton, Southampton General Hospital, Southampton SO9 4XY
and
NON-ENTEROTOXIN-PRODUCING, NON-INVASIVE
W. M.,
SIR,-The article by Dr Levine and his colleagues (May 27, 1119) was of great interest since it provided follow-up infor-
p. mation
on an enteropathogenic E. coli which caused some havoc in the West of Scotland seven and eight years ago.1.2 Since this particular strain (0142:K86:H6) has now been classified as non-invasive and not productive of heat labile or heat stable enterotoxins, on the basis of the tests described in Levine’s paper, I should now like to raise the question of the efficacy of the guineapig eye test3 as an indicator of invasiveness for the human small intestine mucosa in most infective situations. Several workers have implied that the results of the guineapig eye test are applicable to the human small intestine. The histology of the two fatal cases investigated post mortem in 1972 showed well-advanced mucosal repair and persisting crypt abscesses in the small intestine.2 These features suggest to me that the small-intestine mucosa had been invaded. There are other publications which report even more severe findings in the small intestine. This limited experience suggests that an enteropathogenic E. coli may be invasive in the infant human small intestine but non-invasive in the guineapig eye test. If more correlations of this variety could be accomplished the applicability of the guineapig eye test to clinical medicine might be assessed once and for all.
Brownlee Laboratory, Ruchill Hospital, and Pathology Department, Western Infirmary,
JAMES F. BOYD
Glasgow
PITUITARY HORMONES IN DIABETIC KETOACIDOSIS p. 1171) draw the importance of the pituitary hormones in the development of diabetic ketoacidosis. The following casereport emphasises this. A 53-year-old woman with acromegaly and a diabetic glucose-tolerance curve (fasting 7.2, peak, 11-7, 2 h 10.00 mmol/1) received pituitary irradiation (4500 rad) in December, 1976, and was then maintained on bromocriptine 20 mg/day. Her growth hormone fell from more than 200 mU/1 to 34 mU/1 (normal less than 10 mU/1). Prolactin fell to 30 mU/1 (normal 100-400). Random glucose levels were normal. To assess the effect of irradiation bromocriptine was stopped on Jan. 6, 1978. 6 weeks later the patient was admitted as an emergency in diabetic ketoacidosis with a blood-glucose of 42 mmol/1 and heavy ketonuria. After initial stabilisation, bromocriptine was reintroduced at 7.5mg/day, and it was possible to withdraw insulin after one week. Her blood-glucose returned to normal and the subsequent glucose-tolerance curve was non-diabetic (fasting 4-7, peak 8-6, 2 h 5-5mmol/1). Diurnal variation of cortisol was normal (midnight 70,9 A.M. 485nmol/1). 2 weeks before this admission her growth hormone had risen to 138 mU/1 and her prolactin to 555 mU/1. Recent growth hormone on bromocriptine was 40 mU/1. In this patient diabetic ketoacidosis occurred at a time of resurgence of growth hormone and prolactin, without evidence of intercurrent infection or other change in treatment.
SiR,-Dr Barnes and colleagues (June 3,
attention
to
We thank Dr C.
Symons
for
permission
to
Royal Free Hospital, London NW3 2QG
report this
R. M. BERNSTEIN M. C. COLQUHOUN
FLOYD J. FANTELLI Ruben, C. E. Hum. Path. 1975, 6, 157.
1. 2. 3.
Love,
W.
case.
C., and others. Lancet, 1972, ii, 355.
Kennedy, D. H., and others. J. clin. Path. 1973, 26, 731. Sereny, B. Acta microbiol. hung. 1957, 4, 367.
SIR,-In their report of
of malabsorption associated with multiple sclerosis Dr Fantelli and colleagues (May 13, p. 1039) describe villous atrophy in three separate jejunal-biopsy specimens and the entire small intestine at necropsy. With all this material available Fantelli et al. chose to illustrate their letter with a section of jejunal mucosa which has been cut transversely and is totally unsuitable for the assessment of villous architecture. While jejunal biopsy remains the central investigation in patients with malabsorption it is imperative that the biopsy be correctly oriented, fixed, and sectioned so that vertical sections of good quality are obtained. Incorrect orientation and sectioning can lead to artefactual subtotal villous atrophy when the mucosa is completely normal.’ Unless the illustrations show correctly oriented material one must treat reports of the multiplicity of conditions said to be associated with villous atrophy with scepticism.
P. ISAACSON
**This letter has been shown lows.-ED.L.
to
Dr
Fantelli, whose reply fol-
S:R,—The point raised by Dr Isaacson is an important one. must assume, however, that Isaacson is referring to tan-
We
gential sectioning sectioning, for the following reasons: (1) not many would conceive that the diagnosis of lesions compatible with malabsorption would be more difficult on a transverse section of intestine rather than a longitudinal one; (2) the importance of biopsy interpretation lies in the perpendicularity to the muscularis mucosa; and not whether it is transverse or longitudinal; (3) no mention of transverse sectioning is made in Perera’s excellent article,’ but he does deal in detail with tangential artifacts. The recognition of tangential artifacts is crucial in smallbowel biopsy interpretation since it is one of the main sources of misinterpretation. Perera describes several helpful hints for the recognition of tangential artifact. One common artifact produces multiple rows of circular acinar profiles which frequently have no muscularis mucosae present. Our photograph demonstrates at most, two rows of circular acini with an intact muscularis clearly present at the bottom of the photograph. If the specimen were tangential, one might expect either more rows of acini or the lack of muscularis. Our illustration demonstrated a narrow lamina propria. It is difficult to imagine tangential sectioning producing a narrowing of the lamina propria. In fact, Perera mentions expansion of the lamina propria as a product of tangential sectioning. A multilayered surface epithelium is also frequently seen in tangential sections (our photo has a monolayered surface). And finally, Perera describes a warning sign of tangential sectioning-namely, elliptical profiles of cross sectioned crypts. All acini are circular in our
not transverse
photo.
We chose a pre-mortem specimen obtained from our institution because of uniform handling, processing, and staining as well as the almost universal presence of superficial autolysis in post mortem specimens, that, while diagnostically suitable, is not aesthetically suitable for publication. Our illustration demonstrates surface epithelium, absent villi, intact muscularis mucosse, and a narrowed lamina propria with an intense round-cell infiltrate of lymphocytes and plasma cells. We considered these findings sufficient for the diagnosis of an intestinal lesion compatible with malabsorption (which our patient clearly had on clinical and chemical
grounds). Cleveland Clinic, Cleveland, Ohio 44106, U S.A.
1.
Perera, D. R., Weinstein,
ENTEROPATHOGENIC ESCHERICHIA COLI
a case
Department of Pathology, University of Southampton, Southampton General Hospital, Southampton SO9 4XY
and
NON-ENTEROTOXIN-PRODUCING, NON-INVASIVE
W. M.,
SIR,-The article by Dr Levine and his colleagues (May 27, 1119) was of great interest since it provided follow-up infor-
p. mation
on an enteropathogenic E. coli which caused some havoc in the West of Scotland seven and eight years ago.1.2 Since this particular strain (0142:K86:H6) has now been classified as non-invasive and not productive of heat labile or heat stable enterotoxins, on the basis of the tests described in Levine’s paper, I should now like to raise the question of the efficacy of the guineapig eye test3 as an indicator of invasiveness for the human small intestine mucosa in most infective situations. Several workers have implied that the results of the guineapig eye test are applicable to the human small intestine. The histology of the two fatal cases investigated post mortem in 1972 showed well-advanced mucosal repair and persisting crypt abscesses in the small intestine.2 These features suggest to me that the small-intestine mucosa had been invaded. There are other publications which report even more severe findings in the small intestine. This limited experience suggests that an enteropathogenic E. coli may be invasive in the infant human small intestine but non-invasive in the guineapig eye test. If more correlations of this variety could be accomplished the applicability of the guineapig eye test to clinical medicine might be assessed once and for all.
Brownlee Laboratory, Ruchill Hospital, and Pathology Department, Western Infirmary,
JAMES F. BOYD
Glasgow
PITUITARY HORMONES IN DIABETIC KETOACIDOSIS p. 1171) draw the importance of the pituitary hormones in the development of diabetic ketoacidosis. The following casereport emphasises this. A 53-year-old woman with acromegaly and a diabetic glucose-tolerance curve (fasting 7.2, peak, 11-7, 2 h 10.00 mmol/1) received pituitary irradiation (4500 rad) in December, 1976, and was then maintained on bromocriptine 20 mg/day. Her growth hormone fell from more than 200 mU/1 to 34 mU/1 (normal less than 10 mU/1). Prolactin fell to 30 mU/1 (normal 100-400). Random glucose levels were normal. To assess the effect of irradiation bromocriptine was stopped on Jan. 6, 1978. 6 weeks later the patient was admitted as an emergency in diabetic ketoacidosis with a blood-glucose of 42 mmol/1 and heavy ketonuria. After initial stabilisation, bromocriptine was reintroduced at 7.5mg/day, and it was possible to withdraw insulin after one week. Her blood-glucose returned to normal and the subsequent glucose-tolerance curve was non-diabetic (fasting 4-7, peak 8-6, 2 h 5-5mmol/1). Diurnal variation of cortisol was normal (midnight 70,9 A.M. 485nmol/1). 2 weeks before this admission her growth hormone had risen to 138 mU/1 and her prolactin to 555 mU/1. Recent growth hormone on bromocriptine was 40 mU/1. In this patient diabetic ketoacidosis occurred at a time of resurgence of growth hormone and prolactin, without evidence of intercurrent infection or other change in treatment.
SiR,-Dr Barnes and colleagues (June 3,
attention
to
We thank Dr C.
Symons
for
permission
to
Royal Free Hospital, London NW3 2QG
report this
R. M. BERNSTEIN M. C. COLQUHOUN
FLOYD J. FANTELLI Ruben, C. E. Hum. Path. 1975, 6, 157.
1. 2. 3.
Love,
W.
case.
C., and others. Lancet, 1972, ii, 355.
Kennedy, D. H., and others. J. clin. Path. 1973, 26, 731. Sereny, B. Acta microbiol. hung. 1957, 4, 367.
