- Email: [email protected]
DIETARY FIBRE AND EXPERIMENTAL COLON CANCER
843
period at the time of investigation. By contrast, the of patients Cooper et al. had been on a .F.D..for 1-10 (mean 4) years. Whether or not a G.F.D. influences cutaneous IgA deposition in D.H. is controversia1.8.9 However, Harrington and Read8 have stressed that nothing less than complete removal of dietary gluten can be expected to result in disappearance of IgA. Full individual details of the IgA-negative Birmingham patients are not given, but the results of post-G.F.D. small-intestinal biopsies suggest that elimination of dietary gluten was not complete. In no patient had the mucosal abnormality returned completely to normal, and in 1 case the abnormality remained in the severest grade. We think it is wrong to imply, without qualification, that the characteristic cutaneous IgA deposits are not helpful in the diagnosis of D.H. and that they are frequently found in other diseases. To summarise our own experience and views: (1) IgA is not present in the skin in patients with C.D. who do not also have D.H.;2 (2) similar IgA deposits have been found in only 4 of approximately 1300 skin-biopsy specimens of non-D.H. dermatoses;2 (3) demonstration of IgA in the skin remains a very useful diagnostic feature of D.H., and the absence of such deposits is strong evidence against the diagnosis. However, neither criterion should be regarded as absolute, and the possibility (as yet unresolved) that a prolonged G.F.D. may influence IgA deposition in some D.H. patients must be considered. for
a
short
University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE 1 4LP
M. G. C. DAHL JANET M. MARKS
PENICILLIN-ASSOCIATED COLITIS
SIR,-Dr Toffler and colleagues (Sept. 30, p. 707) describe cases of penicillin-associated transient colitis; we have seen
five
two
such cases lately.
24-year-old woman presented after one day of severe colicky abdominal pain and profuse watery diarrhoea which had become bloody. 3 days previously she had started taking oral penicillin V after a dental extraction. She was not taking oral contraceptives. Physical examination was normal apart from mild pyrexia (37-5°C) and bilateral flank tenderness. Sigmoidoscopy revealed liquid bloody stool in the rectal lumen, but the mucosa was normal. Investigations included Hb 15 2 g/dl ; white blood-cells 156x109/1 (neutrophils 83%); E.S.R. 20 mm/h; blood cultures (x3) negative; stool culture (x3), no pathogens. Barium enema examination on the day after admission showed spasm and thumb-printing of the cae cum and ascending colon which had disappeared by the time of a barium follow-through examination 5 days later. The patient’s initial treatment consisted of fluids and oral loperamide only. Within 3 days of admission she was afebrile, pain-free, and passing normal stools, and she has remained symptom-free over 5 months of follow-up. A 21-year-old woman was admitted with 24 h of anorexia followed by profuse vomiting, sharp central abdominal pain, and the passage of loose stools turning to bright blood per rectum. She had been taking oral penicillin for 3 day s for a sore throat, and had been on a low-oestrogen oral contraceptive for 18 months. She was febrile (38 °C) and was very tender suprapubically and in both iliac fossse. Sigmoidoscopy showed blood in the rectum, but the mucosa was normal both visually and on biopsy. Investigations were: Hb 15.9 g/dl; w.B.c. 26-3xlO"/I (neutrophils 86%); E.S.R. 5 mm/h; stool cultures (x3) negative for pathogens. On the second day of her illness A
.
barium enema examination revealed spasm and a coarse sawtooth appearance from the caecum to the mid descending colon. There was no obvious ulceration and the distal colon appeared normal. Her symptoms and signs settled completely without specific treatment in 4 days, when a barium follow-through a
8. 9.
Harringion, C. I., Read, N. W. Br. med. J. 1977, i, 872. Fry, L., Haffenden, G., Wojnarowska, F., Thompson, J. Derm 1978, 99, 31.
showed a normal ileum and a contracted nodular caecum. She has remained well, and a barium enema repeated 3 months after her acute illness was normal. These two cases ran a strikingly similar course with an acute onset suggesting possible intussusception. The distribution and nature of the radiological changes closely resembled those described by Toffler et al. In the second case the contraceptive pill may have been a contributory factor to the development of an acute transient right-sided colitis, but the immediate association in both cases was the administration of oral penicillin for 3 days. A history of intake of this class of antibiotics, the acute onset of painful bloody diarrhoea and fever, combined with negative stool cultures and negative sigmoidoscopy should prompt an early ("instant") barium enema. The characteristic findings here should spare the patient needless steroid therapy or even a
diagnostic laparotomy.
Department of Gastroenterolology, West Middlesex Hospital, Isleworth, Middlesex TW7 6AF
Seah,
P. P. Br.
STEPHEN P. KANE
DIETARY FIBRE AND EXPERIMENTAL COLON CANCER
Sin,—The paper by Dr Fleiszer and others (Sept. 9,
p. 552), purporting to demonstrate the protective effects of dietary fibre against chemically induced rat colon cancer, is misleading
in several respects. Fleiszer et al. cite Wilson and others’ as having shown that "the incidence of bowel cancer in rats was reduced when fibre was added to defined diets". However, Wilson et al. in fact stated "There was no significant difference in the percentage of rats with malignant tumours of the colon with respect to the feeding of bran", and concluded that fibre may protect only against benign lesions. Fleiszer et al. are not justified in concluding that the fibre component of their diets was responsible for the protective effects when these diets differed from each other not only in type (solid or liquid), but also in relation to components other than fibre, such as fats and protein, factors which have previously been shown to exert independent effects on dimethylhydrazine colon carcinogenesis.2,3 In addition, as Dr Heaton and Mr Williamson have pointed out (Oct. 2, p. 784) there were significant caloric differences in the diets used. However, potentially their most misleading conclusion is that "the incidence of colonic carcinoma increased as the dietary fibre content decreased". The incidence of colon carcinoma to which they refer was that assessed at necropsy (no histological or statistical details are given) when the animals were killed at 28 weeks. As Peto4 has pointed out, the connection between such intercurrent death and tumour incidence is subtle. If an animal which would have developed a tumour at a certain time dies (e.g., because it is killed, before the tumour is large enough to be found at necropsy, then the killing of the animal has prevented the discovery of the tumour, resulting in a falsely low tumour incidence. Fleiszer et al. seem to have made this error. In support of these contentions, we recently presented the results of a year-long dietary fibre study similar in principle to that of Fleiszer and others. Dietary fibre, as the only experimental variable, did not significantly affect the time to tumour presentation nor survival of dimethylhydrazine-treated rats. Furthermore, the incidence of colon carcinoma (as proven by histology after necropsy) was 100% at one year in every dietary group, irrespective of the fibre content. Had Fleiszer et al. waited a similar length of time, it is probable that the inci1.
Wilson, R. B., Hutcheson, D. P., Wideman, L. Am. J. clin. Nutr. 1977, 30,
2.
Reddy,
176. B.
S., Nansawa, T., Weisburger, J. H. J. natn. Cancer Inst. 1976,
57, 567 3. Broitman, S. A., Vitale,
B. R.,
IAN G. BARRISON
J. J , Vavrousek-Jakuba, E., Gottlieb, 1977, 40, 2455. 4. Peto, R. Br. J. Cancer, 1974, 29, 101.
L. S. Cancer,
844 dence of colon cancer in their dietary fibre groups would also have approached 100%, thereby invalidating the central tenet of their argument. We contend that. their results do not provide support for the fibre theory. This work was presented to the British Society of Gastroenterology autumn meeting, m Edinburgh, on Sept. 19-23, 1978, and will be published in Gut. P. CRUSE M. R. LEWIN C. G. CLARK
J.
Surgical Unit, University College Hospital Medical School, London WC 1E 6JJ
NON-OCCUPATIONAL EXPOSURE TO ASBESTOS
SiR,—Imake no apology for dismissing, in my letter of Sept. 2, the definition of asbestos-related occupations offered by Hamilton and Hardy.’ They give thirteen such occupations when a full list would run into thousands. Incredibly, they do not list the manufacture of asbestos-cement pipe which accounts for about 40% of all asbestos used in Australia and, I am told, probably a higher proportion.in the United States. My dismissal of this list is described by Dr Vianna and Adele Polan (Sept. 2) as "nihilistic" but then that is what this list is worth-nihil. It is reassuring to know that the "milliner" in Vianna and Polan’s study was in fact a "miller"-who milled talc containing asbestos. But to describe a person so employed simply as a "miller" is not good enough. Most millers mill grains of one sort or another, but if a miller happens to be milling an asbestos-containing talc the matter is of some importance. Likewise, few textile workers are engaged in the manufacture of asbestos-textiles but if that is what a textile worker is doing some interest attaches to the matter. I must still ask exactly what a heat-electric wire worker does and how an elevator insulation worker goes about his work. On the "shoemaker", I remain unrepentant. The reference cited by Vianna and Polan is irrelevant: "Asbestos is another material used as a filler, resulting in generation of dust from sawing and grinding in finishing processes."2 True, but there is no mention of shoes or shoemakers. Why would anyone incorporate asbestos as a filler in a shoe? Inquiry in Australia has discovered no-one in the trade who has ever heard of the practice ; two felt fillers used here in shoe manufacture have been examined and found to contain no asbestos. James Hardie and Co. Ltd, Camellia, New South Wales 2142, Australia
S. F. MCCULLAGH Chief Medical Officer
ENDOCARDITIS WITH ACID-FAST ORGANISM AFTER PORCINE HEART-VALVE REPLACEMENT
SIR The failure by Dr O’Rourke and colleagues (Sept. 23, to isolate mycobacteria from the porcine valve in their patient with infective endocarditis after valve replacement leads us to suggest that the addition of mycobactin to the culture media used for the isolation of mycobacteria in medical
p.686)
laboratories might be considered. Mycobacterial disease in pigs is usually associated with the Mycobacterium am’um/M. intracellulare complex, and it would seem feasible that one of these organisms was involved in this instance. We have found that some M. avium strains, when present in numbers less than 107 vi ible units, require the addition of mycobactin3 for initial growth, and we have obtained a 14-0% increased isolation-rate of M. avium from pig-head lymph-nodes by adding mycobactin to the medium.4 1. Hamilton, A., Hardy, H I.. Industrial Toxicology, setts, 1974. 2 Beliczky, I.. S., Zenz, C Occupational Medicine Applications; p. 788. Chicago, 1975
p. 421. Acton, Massachu-
Principles
3. Matthews, P. R. J., McDiarmid, A., Collins, P., Brown, robiol. 1978, 11, 53. 4. Matthews, P. R. J. Res vet. Sci. 1969, 10, 104
and Practical
Anne, J
med. Mic-
We appreciate your correspondents’ cause for concern that methods used in certain medical laboratories are not always adequate for the isolation of these organisms and suggest that the addition of 3.0 1J.g/ml of mycobactin to the medium and prolonged incubation, up to six months, might have resulted in the isolation of the causal mycobacteria in this instance. It might also have been helpful if the inoculated laboratory animals had been kept for a longer period. The guineapigs might well have reacted to avian P.P.D. tuberculin, although no obvious pathological changes were present. We have also found that C57 mice will usually show some pathological changes, particularly an increase in the size of the spleen after 3-4 months, if infected by these atypical mycobacteria. Research Council Institute for Research on Animal Diseases,
Agricultural
Compton,Newbury, Berkshire,
P. R. J. MATTHEWS A. MCDIARMID
CRYOPRECIPITATE PREPARATION
SIR,—Having read Mr Mason’s paper (July 1, p. 15) and subsequent correspondence we now report some negative findings in our continuing programme to improve the quality of the cryoprecipitate we prepare. Fast-thaw methods are better than air thaw (which takes about 18 h). Introducing a fast water-bath thaw at 4°C improved our factor-vi!! recovery by 20’,(. Thawing takes 12-2 h. Dr Das and Dr Sibinga (July 29, p. 273) imply that the original thaw-syphon method must be adapted before it can be used on a large scale, and our experience confirms this. Further improvement is possible if very thin plasma wafers are used (large bag method)’ or by scaling down and using very small samples.2 . Dr J. F. Davidson and colleagues (personal communication) showed that factor-vin recovery fell if a thawing temperature substantially above 4°C was used. We have been looking at methods of applying energy to the frozen plasma which will result in heat being generated throughout the thickness of the wafer of plasma. Highly penetrating electromagnetic radiation might be suitable, and a domestic microwave oven was obtained. This appliance generates radiation at 42 GHz and the energy output is a little under 3 kW. Mollison3 has reservations about the use of radiofrequency blood warmers but Sherman and Dorner4used a microwave oven to thaw fresh frozen plasma for transfusion. We found that the outside of the plastic bag was heated to nearly 500C and protein denaturation was produced even by exposure-times (90-120 s) so slow that sizeable lumps of frozen plasma were still present. For every millimetre it travels through the target a highly penetrating radiation leaves a very small proportion of its total energy to be converted into heat. Thus the target is affected almost uniformly along the path of the rays. Unfortunately, 4.2 GHz radiation is almost entirely converted into heat by as little as 5 mm of ice. Thus the energy was concentrated on the top 5 mm of the plasma wafer. As the thawed plasma absorbs the radiation even more than the solid phase, proteins are denatured even when lumps of ice are still
present. We are now investigating other methods of ergy to frozen plasma. and West of Scotland Blood Transfusion Service,
Glasgow
Law Hospital, Carluke ML8 5FS, Lanarkshire
delivering
en-
R.
J. CRAWFORD A. BARR R. MITCHELL
Slichter, S. J., Counts, R. B., Henderson, R., Harker, L. A., Transfusion, 1976, 16, 616. 2. Kasper, C. K., Myhre, B. A., McDonald, J. D., Nakasako, Y., Feinstein, D.I. Ibid. 1975, 15, 312. 3. Mollison, P. L. Blood Transfusion in Clinical Medicine; p. 581. Oxford 1.
1972. 4. Sherman, L
A., Dorner, I. M. Transfusion, 1974, 14, 595.
period at the time of investigation. By contrast, the of patients Cooper et al. had been on a .F.D..for 1-10 (mean 4) years. Whether or not a G.F.D. influences cutaneous IgA deposition in D.H. is controversia1.8.9 However, Harrington and Read8 have stressed that nothing less than complete removal of dietary gluten can be expected to result in disappearance of IgA. Full individual details of the IgA-negative Birmingham patients are not given, but the results of post-G.F.D. small-intestinal biopsies suggest that elimination of dietary gluten was not complete. In no patient had the mucosal abnormality returned completely to normal, and in 1 case the abnormality remained in the severest grade. We think it is wrong to imply, without qualification, that the characteristic cutaneous IgA deposits are not helpful in the diagnosis of D.H. and that they are frequently found in other diseases. To summarise our own experience and views: (1) IgA is not present in the skin in patients with C.D. who do not also have D.H.;2 (2) similar IgA deposits have been found in only 4 of approximately 1300 skin-biopsy specimens of non-D.H. dermatoses;2 (3) demonstration of IgA in the skin remains a very useful diagnostic feature of D.H., and the absence of such deposits is strong evidence against the diagnosis. However, neither criterion should be regarded as absolute, and the possibility (as yet unresolved) that a prolonged G.F.D. may influence IgA deposition in some D.H. patients must be considered. for
a
short
University Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE 1 4LP
M. G. C. DAHL JANET M. MARKS
PENICILLIN-ASSOCIATED COLITIS
SIR,-Dr Toffler and colleagues (Sept. 30, p. 707) describe cases of penicillin-associated transient colitis; we have seen
five
two
such cases lately.
24-year-old woman presented after one day of severe colicky abdominal pain and profuse watery diarrhoea which had become bloody. 3 days previously she had started taking oral penicillin V after a dental extraction. She was not taking oral contraceptives. Physical examination was normal apart from mild pyrexia (37-5°C) and bilateral flank tenderness. Sigmoidoscopy revealed liquid bloody stool in the rectal lumen, but the mucosa was normal. Investigations included Hb 15 2 g/dl ; white blood-cells 156x109/1 (neutrophils 83%); E.S.R. 20 mm/h; blood cultures (x3) negative; stool culture (x3), no pathogens. Barium enema examination on the day after admission showed spasm and thumb-printing of the cae cum and ascending colon which had disappeared by the time of a barium follow-through examination 5 days later. The patient’s initial treatment consisted of fluids and oral loperamide only. Within 3 days of admission she was afebrile, pain-free, and passing normal stools, and she has remained symptom-free over 5 months of follow-up. A 21-year-old woman was admitted with 24 h of anorexia followed by profuse vomiting, sharp central abdominal pain, and the passage of loose stools turning to bright blood per rectum. She had been taking oral penicillin for 3 day s for a sore throat, and had been on a low-oestrogen oral contraceptive for 18 months. She was febrile (38 °C) and was very tender suprapubically and in both iliac fossse. Sigmoidoscopy showed blood in the rectum, but the mucosa was normal both visually and on biopsy. Investigations were: Hb 15.9 g/dl; w.B.c. 26-3xlO"/I (neutrophils 86%); E.S.R. 5 mm/h; stool cultures (x3) negative for pathogens. On the second day of her illness A
.
barium enema examination revealed spasm and a coarse sawtooth appearance from the caecum to the mid descending colon. There was no obvious ulceration and the distal colon appeared normal. Her symptoms and signs settled completely without specific treatment in 4 days, when a barium follow-through a
8. 9.
Harringion, C. I., Read, N. W. Br. med. J. 1977, i, 872. Fry, L., Haffenden, G., Wojnarowska, F., Thompson, J. Derm 1978, 99, 31.
showed a normal ileum and a contracted nodular caecum. She has remained well, and a barium enema repeated 3 months after her acute illness was normal. These two cases ran a strikingly similar course with an acute onset suggesting possible intussusception. The distribution and nature of the radiological changes closely resembled those described by Toffler et al. In the second case the contraceptive pill may have been a contributory factor to the development of an acute transient right-sided colitis, but the immediate association in both cases was the administration of oral penicillin for 3 days. A history of intake of this class of antibiotics, the acute onset of painful bloody diarrhoea and fever, combined with negative stool cultures and negative sigmoidoscopy should prompt an early ("instant") barium enema. The characteristic findings here should spare the patient needless steroid therapy or even a
diagnostic laparotomy.
Department of Gastroenterolology, West Middlesex Hospital, Isleworth, Middlesex TW7 6AF
Seah,
P. P. Br.
STEPHEN P. KANE
DIETARY FIBRE AND EXPERIMENTAL COLON CANCER
Sin,—The paper by Dr Fleiszer and others (Sept. 9,
p. 552), purporting to demonstrate the protective effects of dietary fibre against chemically induced rat colon cancer, is misleading
in several respects. Fleiszer et al. cite Wilson and others’ as having shown that "the incidence of bowel cancer in rats was reduced when fibre was added to defined diets". However, Wilson et al. in fact stated "There was no significant difference in the percentage of rats with malignant tumours of the colon with respect to the feeding of bran", and concluded that fibre may protect only against benign lesions. Fleiszer et al. are not justified in concluding that the fibre component of their diets was responsible for the protective effects when these diets differed from each other not only in type (solid or liquid), but also in relation to components other than fibre, such as fats and protein, factors which have previously been shown to exert independent effects on dimethylhydrazine colon carcinogenesis.2,3 In addition, as Dr Heaton and Mr Williamson have pointed out (Oct. 2, p. 784) there were significant caloric differences in the diets used. However, potentially their most misleading conclusion is that "the incidence of colonic carcinoma increased as the dietary fibre content decreased". The incidence of colon carcinoma to which they refer was that assessed at necropsy (no histological or statistical details are given) when the animals were killed at 28 weeks. As Peto4 has pointed out, the connection between such intercurrent death and tumour incidence is subtle. If an animal which would have developed a tumour at a certain time dies (e.g., because it is killed, before the tumour is large enough to be found at necropsy, then the killing of the animal has prevented the discovery of the tumour, resulting in a falsely low tumour incidence. Fleiszer et al. seem to have made this error. In support of these contentions, we recently presented the results of a year-long dietary fibre study similar in principle to that of Fleiszer and others. Dietary fibre, as the only experimental variable, did not significantly affect the time to tumour presentation nor survival of dimethylhydrazine-treated rats. Furthermore, the incidence of colon carcinoma (as proven by histology after necropsy) was 100% at one year in every dietary group, irrespective of the fibre content. Had Fleiszer et al. waited a similar length of time, it is probable that the inci1.
Wilson, R. B., Hutcheson, D. P., Wideman, L. Am. J. clin. Nutr. 1977, 30,
2.
Reddy,
176. B.
S., Nansawa, T., Weisburger, J. H. J. natn. Cancer Inst. 1976,
57, 567 3. Broitman, S. A., Vitale,
B. R.,
IAN G. BARRISON
J. J , Vavrousek-Jakuba, E., Gottlieb, 1977, 40, 2455. 4. Peto, R. Br. J. Cancer, 1974, 29, 101.
L. S. Cancer,
844 dence of colon cancer in their dietary fibre groups would also have approached 100%, thereby invalidating the central tenet of their argument. We contend that. their results do not provide support for the fibre theory. This work was presented to the British Society of Gastroenterology autumn meeting, m Edinburgh, on Sept. 19-23, 1978, and will be published in Gut. P. CRUSE M. R. LEWIN C. G. CLARK
J.
Surgical Unit, University College Hospital Medical School, London WC 1E 6JJ
NON-OCCUPATIONAL EXPOSURE TO ASBESTOS
SiR,—Imake no apology for dismissing, in my letter of Sept. 2, the definition of asbestos-related occupations offered by Hamilton and Hardy.’ They give thirteen such occupations when a full list would run into thousands. Incredibly, they do not list the manufacture of asbestos-cement pipe which accounts for about 40% of all asbestos used in Australia and, I am told, probably a higher proportion.in the United States. My dismissal of this list is described by Dr Vianna and Adele Polan (Sept. 2) as "nihilistic" but then that is what this list is worth-nihil. It is reassuring to know that the "milliner" in Vianna and Polan’s study was in fact a "miller"-who milled talc containing asbestos. But to describe a person so employed simply as a "miller" is not good enough. Most millers mill grains of one sort or another, but if a miller happens to be milling an asbestos-containing talc the matter is of some importance. Likewise, few textile workers are engaged in the manufacture of asbestos-textiles but if that is what a textile worker is doing some interest attaches to the matter. I must still ask exactly what a heat-electric wire worker does and how an elevator insulation worker goes about his work. On the "shoemaker", I remain unrepentant. The reference cited by Vianna and Polan is irrelevant: "Asbestos is another material used as a filler, resulting in generation of dust from sawing and grinding in finishing processes."2 True, but there is no mention of shoes or shoemakers. Why would anyone incorporate asbestos as a filler in a shoe? Inquiry in Australia has discovered no-one in the trade who has ever heard of the practice ; two felt fillers used here in shoe manufacture have been examined and found to contain no asbestos. James Hardie and Co. Ltd, Camellia, New South Wales 2142, Australia
S. F. MCCULLAGH Chief Medical Officer
ENDOCARDITIS WITH ACID-FAST ORGANISM AFTER PORCINE HEART-VALVE REPLACEMENT
SIR The failure by Dr O’Rourke and colleagues (Sept. 23, to isolate mycobacteria from the porcine valve in their patient with infective endocarditis after valve replacement leads us to suggest that the addition of mycobactin to the culture media used for the isolation of mycobacteria in medical
p.686)
laboratories might be considered. Mycobacterial disease in pigs is usually associated with the Mycobacterium am’um/M. intracellulare complex, and it would seem feasible that one of these organisms was involved in this instance. We have found that some M. avium strains, when present in numbers less than 107 vi ible units, require the addition of mycobactin3 for initial growth, and we have obtained a 14-0% increased isolation-rate of M. avium from pig-head lymph-nodes by adding mycobactin to the medium.4 1. Hamilton, A., Hardy, H I.. Industrial Toxicology, setts, 1974. 2 Beliczky, I.. S., Zenz, C Occupational Medicine Applications; p. 788. Chicago, 1975
p. 421. Acton, Massachu-
Principles
3. Matthews, P. R. J., McDiarmid, A., Collins, P., Brown, robiol. 1978, 11, 53. 4. Matthews, P. R. J. Res vet. Sci. 1969, 10, 104
and Practical
Anne, J
med. Mic-
We appreciate your correspondents’ cause for concern that methods used in certain medical laboratories are not always adequate for the isolation of these organisms and suggest that the addition of 3.0 1J.g/ml of mycobactin to the medium and prolonged incubation, up to six months, might have resulted in the isolation of the causal mycobacteria in this instance. It might also have been helpful if the inoculated laboratory animals had been kept for a longer period. The guineapigs might well have reacted to avian P.P.D. tuberculin, although no obvious pathological changes were present. We have also found that C57 mice will usually show some pathological changes, particularly an increase in the size of the spleen after 3-4 months, if infected by these atypical mycobacteria. Research Council Institute for Research on Animal Diseases,
Agricultural
Compton,Newbury, Berkshire,
P. R. J. MATTHEWS A. MCDIARMID
CRYOPRECIPITATE PREPARATION
SIR,—Having read Mr Mason’s paper (July 1, p. 15) and subsequent correspondence we now report some negative findings in our continuing programme to improve the quality of the cryoprecipitate we prepare. Fast-thaw methods are better than air thaw (which takes about 18 h). Introducing a fast water-bath thaw at 4°C improved our factor-vi!! recovery by 20’,(. Thawing takes 12-2 h. Dr Das and Dr Sibinga (July 29, p. 273) imply that the original thaw-syphon method must be adapted before it can be used on a large scale, and our experience confirms this. Further improvement is possible if very thin plasma wafers are used (large bag method)’ or by scaling down and using very small samples.2 . Dr J. F. Davidson and colleagues (personal communication) showed that factor-vin recovery fell if a thawing temperature substantially above 4°C was used. We have been looking at methods of applying energy to the frozen plasma which will result in heat being generated throughout the thickness of the wafer of plasma. Highly penetrating electromagnetic radiation might be suitable, and a domestic microwave oven was obtained. This appliance generates radiation at 42 GHz and the energy output is a little under 3 kW. Mollison3 has reservations about the use of radiofrequency blood warmers but Sherman and Dorner4used a microwave oven to thaw fresh frozen plasma for transfusion. We found that the outside of the plastic bag was heated to nearly 500C and protein denaturation was produced even by exposure-times (90-120 s) so slow that sizeable lumps of frozen plasma were still present. For every millimetre it travels through the target a highly penetrating radiation leaves a very small proportion of its total energy to be converted into heat. Thus the target is affected almost uniformly along the path of the rays. Unfortunately, 4.2 GHz radiation is almost entirely converted into heat by as little as 5 mm of ice. Thus the energy was concentrated on the top 5 mm of the plasma wafer. As the thawed plasma absorbs the radiation even more than the solid phase, proteins are denatured even when lumps of ice are still
present. We are now investigating other methods of ergy to frozen plasma. and West of Scotland Blood Transfusion Service,
Glasgow
Law Hospital, Carluke ML8 5FS, Lanarkshire
delivering
en-
R.
J. CRAWFORD A. BARR R. MITCHELL
Slichter, S. J., Counts, R. B., Henderson, R., Harker, L. A., Transfusion, 1976, 16, 616. 2. Kasper, C. K., Myhre, B. A., McDonald, J. D., Nakasako, Y., Feinstein, D.I. Ibid. 1975, 15, 312. 3. Mollison, P. L. Blood Transfusion in Clinical Medicine; p. 581. Oxford 1.
1972. 4. Sherman, L
A., Dorner, I. M. Transfusion, 1974, 14, 595.