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PROSTACYCLIN IN PERIPHERAL VASCULAR DISEASE
40 intrinsic factor. The Schilling test measures the absorption of unbound cobalamin and thus does not detect patients whose only defect is malabsorption of dietary cobalamin. Such situationshave been reported after partial after vagotomy 3 , among patients with gastric ulcer, and during cimetidine therapy.5 The diagnosis of cobalamin deficiency in these cases is sometimes further complicated because achlorhydria-related malabsorption of dietary iron may obscure the morphological features of cobalamin deficiency.Most significant of all is cobalamin deficient anaemia associated with repeatedly normal Schilling test results and malabsorption of protein-bound cobalamin. 7,8 Other difficulties which occasionally arise with the Schilling test are apparent malabsorption due to incomplete urine collection, renal dysfunction, or inadequate flushing with non-radioactive cobalamin; apparent normal absorption due to a previous Schilling test or administration of other isotopes, and inappropriate low results when the test is repeated with an oral intrinsic factor supplement due to high concentrations of intrinsic factor antibodies in the patient’s gastric juice or to a "macrocytic" distal ileum in untreated
f astrectomy 2,
patients. We conclude that the Schilling test, like most clinically useful tests, is subject to a number of technical and interpretative errors. Thus neither the serum cobalamin alone nor the Schilling test alone will invariably indicate the presence or absence of cobalamin deficiency. In some circumstances a low serum cobalamin and a normal Schilling test result are consistent with cobalamin deficiency and can be reconciled if the protein-bound cobalamin absorption test is performed.
A. M. STREETER F. A. BATHUR General Hospital, Concord, New South Wales 2139, Australia
Repatriation
B. J. ARNOLD G. G. CRANE M. T. PHEILS
PROSTACYCLIN IN PERIPHERAL VASCULAR DISEASE
SIR,-Although I note with interest Dr Olsson’s observations (Nov. 15, p. 1076) on the use of prostacyclin (PGI2) in eight patients with peripheral vascular disease, it is difficult to appreciate what this adds to the observational studies performed on five9and subsequently thirtylo similar patients published by Szczeklik’s group. Such data as these are provocative when novel; however, repeated uncontrolled studies at best add little and at worst may serve to perpetuate an illusion. Although these statements are relevant to the evaluation of treatment in any disease they seem particularly apposite to peripheral vascular disease in which bed rest
alone may be of benefit.
Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, U. S.A.
GARRET A. FITZGERALD
K, Ripley D, Doscherholmen A. Vitamin B12 absorption tests: Their unreliability in postgastrectomy states. JAMA 1971, 216: 1167-71. Streeter AM, Duraiappah B, Boyle R, O’Neill BJ, Pheils MT Malabsorption of vitamin B12 after vagotomy Am J Surg 1974; 128: 340-43. Streeter AM, Duncombe VM, Boyle R, Pheils MT. A simple method of measuring the absorption of protein-bound vitamin B12 Aust NZ J Med 1975; 5: 382 Steinberg WM, King CE, Toskes PP. Malabsorption of protein-bound cobalamin but not unbound cobalamin during cimetidine administration. Dig Dis Sci 1980, 25:
2. Mahmud 3
4. 5.
188-92. 6. Chanarin I The megaloblastic anaemias. Oxford Blackwell Scientific Publications, 1979; 388 7. Streeter AM, Shum HY, Duncombe VM, Hewson JW, Thorpe MEC. Vitamin B12 malabsorption associated with a normal Schilling test result Med J Aust 1976, 1: 54-5. 8 King CE, Leibach J, Toskes PP. Clinically significant vitamin B12 deficiency secondary to malabsorption of protein-bound vitamin B12 . Dig Dis Sci 1979; 24: 397-402 9. Szczeklik
A, Skawinski S, Gluszko P, Nizankowski R, Szczeklik J, Gryglewski RJ. Successful therapy of advanced arteriosclerosis obliterans with prostacyclin, Lancet 1979; i: 1111-14. 10. Szczeklik A, Gryglewski RJ, Nizankowski R, Skawinski S, Gluszko P, Korbut R Prostacyclin therapy in peripheral arterial disease Thromb Res 1980; 19: 191-99.
BREAST ASPIRATION CYTOLOGY
SIR,-We agree with Dr Coleman (Nov. 15, p. 1083) that fine needle aspiration cytology should be used complementary to rapid "frozen" section in the diagnosis of breast cancer and not aspire to replace it. We base our experience on more than 4000 breast needle aspirates a year of which 90% are from solid tumours and include about 400 carcinomas. The needle aspirate service has had two major effects in this hospital. Firstly, increasing the accuracy of preoperative diagnosis so that, in conjunction with clinical examination and mammography, carcinomas are diagnosed and the patients investigated for metastases-i.e., replacing needle biopsy-and secondly, greatly reducing the number of excisions of benign disease in women with diffuse nodularity in whom there are debatable clinical reasons for biopsy. Frozen section is still needed to help decide the extent of surgical excision and we have seen a number of in-situ carcinomas that have had positive aspirates. We think that the science of breast needle aspiration cytology is still in a developing phase in this ,country and that recommendations to abandon frozen section are premature and could lead to mastectomy for benign breast disease. P. A. TROTT Breast Unit, J. A. MCKINNA Royal Marsden Hospital, London SW3 6JJ
PONTIAC
J.-C. GAZET
FEVER, AMOEBAE, AND LEGIONELLAE
SIR,-I should like to reply to the observations of Nagington and Smith! on my letter about Pontiac fever.2still prefer the hypothesis that the antibody to Legionella pneumophila seen in many cases of Pontiac fever3,4 arises mainly from a mild infection, rather than solely from exposure to dead legionellae or their antigenic debris. This is supported by the isolation of L. pneumophila from the sentinel guineapig exposed to the air of the Pontiac Health Department during investigation of the outbreak there,3 and the longer duration of symptoms seen in some cases of Pontiac fever compared with humidifier fever.2 Amoebae containing ingested legionellae may act as an immunising stimulus as Nagington and Smith suggest,1 but there are also epidemiological grounds for proor a vesicle of legionellae posing that an amoeba full of legionellae, 5 may be infective particles for man. Whether a legionella can infect an amoeba depends on the species, serogroup, strain, and fitness of the legionella, the species, strain and fitness of the amoeba, the ambient temperature,and other interacting factors. With some recent isolates of amoebae, the first amoebae to come into contact with suitable legionellae become infected, and numerous infected amoebae, and vesicles containing legionellae, can be seen at this time. Later observations indicated that amoebae digest legionellae and the remains of lysed amoebae, leaving little evidence that infection has occurred. This tends to happen particularly when large numbers of amoebae are used. It may be that extracellular bacteriolytic enzymes produced by amoebae, lysosomal enzymes released by lysis of infected amoebae, and enzymes produced by the growth of klebsiella forming the food of the amoebae, when present in sufficient concentrations, over a long enough period of time, so weaken the legionellae that they may no longer be infective. The amoebae may also become better equipped to counter infection. 250C is about the lowest temperature at which growth ofL. pneumophila occurs in vitro. 6,7 Philadelphia-I 1 2
3
4.
Nagington J, Smith DJ Pontiac fever and amoebae Lancet 1980, ii: 1241 Rowbotham TJ Pontiac fever explained? Lancet 1980, ii: 969 Glick TH, Gregg MB, Berman B, Mallison G, Rhodes Jr WW, Kassanoff I. Pontiac fever: an epidemic of unknown etiology in a health department: I Clinical and epidemiologic aspects. Am J Epidemiol 1978; 107: 149-60 Fraser DW, Deubner DC, Hill DL, Gilliam DK Non-pneumonic, short-incubation period legionellosis (Pontiac fever) in men who cleaned a steam turbine condenser
Science 1979; 205: 690-91 5 Rowbotham TJ Preliminary report on the pathogenicity of Legionella pneumophila for freshwater and soil amoebae J Clin Pathol 1980; 33: 1179-83 6. Feeley JC, Gorman GW, Weaver RE, Mackel DC, Smith HW Primary isolation media for Legionnaires’ disease bacterium J Clin Microbiol 1978; 8: 320-25. 7 Pine L, George JR, Reeves MW, Harrell WK Development ofa chemically defined liquid medium for growth of Logionella pnenmophila. J Clin Microbiol 1979; 9: 615-26
f astrectomy 2,
patients. We conclude that the Schilling test, like most clinically useful tests, is subject to a number of technical and interpretative errors. Thus neither the serum cobalamin alone nor the Schilling test alone will invariably indicate the presence or absence of cobalamin deficiency. In some circumstances a low serum cobalamin and a normal Schilling test result are consistent with cobalamin deficiency and can be reconciled if the protein-bound cobalamin absorption test is performed.
A. M. STREETER F. A. BATHUR General Hospital, Concord, New South Wales 2139, Australia
Repatriation
B. J. ARNOLD G. G. CRANE M. T. PHEILS
PROSTACYCLIN IN PERIPHERAL VASCULAR DISEASE
SIR,-Although I note with interest Dr Olsson’s observations (Nov. 15, p. 1076) on the use of prostacyclin (PGI2) in eight patients with peripheral vascular disease, it is difficult to appreciate what this adds to the observational studies performed on five9and subsequently thirtylo similar patients published by Szczeklik’s group. Such data as these are provocative when novel; however, repeated uncontrolled studies at best add little and at worst may serve to perpetuate an illusion. Although these statements are relevant to the evaluation of treatment in any disease they seem particularly apposite to peripheral vascular disease in which bed rest
alone may be of benefit.
Department of Pharmacology, School of Medicine, Vanderbilt University, Nashville, Tennessee 37232, U. S.A.
GARRET A. FITZGERALD
K, Ripley D, Doscherholmen A. Vitamin B12 absorption tests: Their unreliability in postgastrectomy states. JAMA 1971, 216: 1167-71. Streeter AM, Duraiappah B, Boyle R, O’Neill BJ, Pheils MT Malabsorption of vitamin B12 after vagotomy Am J Surg 1974; 128: 340-43. Streeter AM, Duncombe VM, Boyle R, Pheils MT. A simple method of measuring the absorption of protein-bound vitamin B12 Aust NZ J Med 1975; 5: 382 Steinberg WM, King CE, Toskes PP. Malabsorption of protein-bound cobalamin but not unbound cobalamin during cimetidine administration. Dig Dis Sci 1980, 25:
2. Mahmud 3
4. 5.
188-92. 6. Chanarin I The megaloblastic anaemias. Oxford Blackwell Scientific Publications, 1979; 388 7. Streeter AM, Shum HY, Duncombe VM, Hewson JW, Thorpe MEC. Vitamin B12 malabsorption associated with a normal Schilling test result Med J Aust 1976, 1: 54-5. 8 King CE, Leibach J, Toskes PP. Clinically significant vitamin B12 deficiency secondary to malabsorption of protein-bound vitamin B12 . Dig Dis Sci 1979; 24: 397-402 9. Szczeklik
A, Skawinski S, Gluszko P, Nizankowski R, Szczeklik J, Gryglewski RJ. Successful therapy of advanced arteriosclerosis obliterans with prostacyclin, Lancet 1979; i: 1111-14. 10. Szczeklik A, Gryglewski RJ, Nizankowski R, Skawinski S, Gluszko P, Korbut R Prostacyclin therapy in peripheral arterial disease Thromb Res 1980; 19: 191-99.
BREAST ASPIRATION CYTOLOGY
SIR,-We agree with Dr Coleman (Nov. 15, p. 1083) that fine needle aspiration cytology should be used complementary to rapid "frozen" section in the diagnosis of breast cancer and not aspire to replace it. We base our experience on more than 4000 breast needle aspirates a year of which 90% are from solid tumours and include about 400 carcinomas. The needle aspirate service has had two major effects in this hospital. Firstly, increasing the accuracy of preoperative diagnosis so that, in conjunction with clinical examination and mammography, carcinomas are diagnosed and the patients investigated for metastases-i.e., replacing needle biopsy-and secondly, greatly reducing the number of excisions of benign disease in women with diffuse nodularity in whom there are debatable clinical reasons for biopsy. Frozen section is still needed to help decide the extent of surgical excision and we have seen a number of in-situ carcinomas that have had positive aspirates. We think that the science of breast needle aspiration cytology is still in a developing phase in this ,country and that recommendations to abandon frozen section are premature and could lead to mastectomy for benign breast disease. P. A. TROTT Breast Unit, J. A. MCKINNA Royal Marsden Hospital, London SW3 6JJ
PONTIAC
J.-C. GAZET
FEVER, AMOEBAE, AND LEGIONELLAE
SIR,-I should like to reply to the observations of Nagington and Smith! on my letter about Pontiac fever.2still prefer the hypothesis that the antibody to Legionella pneumophila seen in many cases of Pontiac fever3,4 arises mainly from a mild infection, rather than solely from exposure to dead legionellae or their antigenic debris. This is supported by the isolation of L. pneumophila from the sentinel guineapig exposed to the air of the Pontiac Health Department during investigation of the outbreak there,3 and the longer duration of symptoms seen in some cases of Pontiac fever compared with humidifier fever.2 Amoebae containing ingested legionellae may act as an immunising stimulus as Nagington and Smith suggest,1 but there are also epidemiological grounds for proor a vesicle of legionellae posing that an amoeba full of legionellae, 5 may be infective particles for man. Whether a legionella can infect an amoeba depends on the species, serogroup, strain, and fitness of the legionella, the species, strain and fitness of the amoeba, the ambient temperature,and other interacting factors. With some recent isolates of amoebae, the first amoebae to come into contact with suitable legionellae become infected, and numerous infected amoebae, and vesicles containing legionellae, can be seen at this time. Later observations indicated that amoebae digest legionellae and the remains of lysed amoebae, leaving little evidence that infection has occurred. This tends to happen particularly when large numbers of amoebae are used. It may be that extracellular bacteriolytic enzymes produced by amoebae, lysosomal enzymes released by lysis of infected amoebae, and enzymes produced by the growth of klebsiella forming the food of the amoebae, when present in sufficient concentrations, over a long enough period of time, so weaken the legionellae that they may no longer be infective. The amoebae may also become better equipped to counter infection. 250C is about the lowest temperature at which growth ofL. pneumophila occurs in vitro. 6,7 Philadelphia-I 1 2
3
4.
Nagington J, Smith DJ Pontiac fever and amoebae Lancet 1980, ii: 1241 Rowbotham TJ Pontiac fever explained? Lancet 1980, ii: 969 Glick TH, Gregg MB, Berman B, Mallison G, Rhodes Jr WW, Kassanoff I. Pontiac fever: an epidemic of unknown etiology in a health department: I Clinical and epidemiologic aspects. Am J Epidemiol 1978; 107: 149-60 Fraser DW, Deubner DC, Hill DL, Gilliam DK Non-pneumonic, short-incubation period legionellosis (Pontiac fever) in men who cleaned a steam turbine condenser
Science 1979; 205: 690-91 5 Rowbotham TJ Preliminary report on the pathogenicity of Legionella pneumophila for freshwater and soil amoebae J Clin Pathol 1980; 33: 1179-83 6. Feeley JC, Gorman GW, Weaver RE, Mackel DC, Smith HW Primary isolation media for Legionnaires’ disease bacterium J Clin Microbiol 1978; 8: 320-25. 7 Pine L, George JR, Reeves MW, Harrell WK Development ofa chemically defined liquid medium for growth of Logionella pnenmophila. J Clin Microbiol 1979; 9: 615-26