605 of the organism, carriage in the intestine, and then, sometimes, invasion of the bloodstream.4 Complications may also occur (toxicosis, dehydration) bur those affected-usually recover without antimicrobial treatment. Isolation of Campylobacter from the stools does not automatically imply the need for antibiotics; the decision should be taken on clinical and epidemiological grounds. Nevertheless intestinal infection may sometimes be followed by invasion of bloodstream, perhaps due to diarrhoea, modification of intestinal flora, or immunological deficiency.4 We have seen only seven cases of septicxmia in 5 years. In five of them the same Campylobacter was isolated on the same occasion from both stools and blood. Dr A. Wilson (Edinburgh) has pointed out that Campylobacter bacteraemia may be common in severe enteritis, but that we have been unaware of this because enteritis is most common in children and blood cultures -are not routine when children are admitted to hospital with fever and diarrhoea. Better knowledge of the organism and its cultural requirements may allow bacteriologists to respond to this suggestion.
gestion !
! ,.
S. LAUWERS M. DE BOECK J. P. BUTZLER
Department of Microbiology, St Pierre Hospital, 1000 Brussels, Belgium
SMOKING AND DIABETIC NEPHROPATHY
Sm,—Little is known about factors influencing the course and development of diabetic microangiopathy. One report of a possible relation between cigarette smoking and proliferative retinopathy’ is not wholly convincing because smoking and non-smoking diabetics were not sufficiently matched for type and duration of diabetes. Nephropathy, one manifestation of diabetic microangiopathy, is the most frequent cause of death in young diaPREVALENCE OF NEPHROPATHY IN SMOKING AND NON-SMOKING PATIENTS WITH
INSULIN-DEPENDENT, JUVENILE-ONSET DIABETES
significantly higher frequency of diabetic nephropathy found among cigarette smokers (table). The prevalence of hypertension did not vary with smoking habits. Since nephropathy is the most serious complication in longterm juvenile diabetes2.3 and since cigarette smoking should be avoided for other reasons it would be of interest if other groups were to confirm this observation. J. SANDAHL CHRISTIANSEN Steno Memorial Hospital, DK-2820 Gentofte, Copenhagen, Denmark J. NERUP A
was
MULTIPLE SCLEROSIS AND CANINE DISTEMPER
SiR,—An epidemiological study of familial multiple sclerosis (M.S.) suggesting a possible association between dogs and rt.s.l was criticised in your correspondence columns last year.2-6 Poskanzer et al.2 found no association between house pets and M.s. in the Orkney and Shetland Islands, although they noted that a high proportion of both control and M.s. groups were exposed to house pets. Epidemiological studies have also been done in the United States, the results suggesting an increased exposure of some M.s. patients to dogs with a distemper-likeillness before clinical onset of M.S.l,7,8 Bauer and Wikstrom3 in West Germany did not find a relationship between dogs and M.S., but again they did find more dogs thought to have distemper in the ns.s. group.’ Canine distemper virus (C.D.V.) is a paramyxovirus which can produce a neurological demyelinating disease in dogs with many similarities to M.s.9-13 Clinically distemper may be more common in cold weather,13 and these environmental conditions might increase contact between infectious dogs and man. Many of the characteristics of c.D.v. and its canine vector, in close association with man, could account for some of the geographical and cultural peculiarities seen in M.s. distribution.7,14,15 Preliminary serological studies have shown raised serum antibodies to C.D.v. in M.s. patients, as measured by immunonuorescence (a technique which, however, may not distinguish c.D.v. from other paramyxoviruses, such as measles virus).’ In view of these findings it seems possible that the development of M.s. may involve transmission of a virus from animal to man and that c..v. is a prime candidate.1.7.8,16 With this hypothesis in mind, we have been examining the apparently anomalous prevalence of M.s. in the Orkney and Shetland Islands as compared with the Faeroe Islands, particularly with respect to disease patterns of
distemper.
-
Orkney and Shetland the prevalence of M.s. is as high as 300 per 100 000 population,2 whereas in the Faeroe Islands (population 40 000) some 300 km to the north-west, no cases of M.s. were recorded from 1929 to 1943 and only 2 cases between 1960 and 1974 in the Faeroese" (who have many cultural and other similarities to the inhabitants of the Orkney and Shetland Islands). However, from 1944 to 1960 the Faeroe Islands experienced an "epidemic" of M.s. with 18 definite cases Kurtzke and Hyllesred17 suggested that these In
+C=Daily cigarette smoking for more than one year. -C=Never smoked cigarettes or cigarette smoking less than one year. tChi-square test. ’
so we have looked for a link between cigarette smokand diabetic nephropathy. The prevalence of diabetic ing nephropathy in a consecutive series of 238 insulin-dependent, juvenile-onset (before age 31) diabetics was related to current and previous smoking habits and to duration of disease. Diabetic nephropathy was defined as a raised serum-creatinine and/or persistent proteinuria without a history or clinical signs of non-diabetic renal disease. Cigarette smokers were defined as patients who had smoked at least 10 cigarettes a day for more than a year.
betics,2.3
4. Butzler,
J. P., Dekegel, D., Hubrechts, J. M., Lauwers, S., Zissis, G. Paper presented at joint meeting of British Society for the Study of Infection and the Infectious Diseases Society of America, held in Glasgow in 1976. 1. Pantkau, M. E., Boys, T. A. S., Winship, B., Grace, M. Diabetes, 1977, 26,
46. 2. Deckert, T., Poulsen, J. E., Larsen, M. Acta endocr. 1976, suppl. 203, 3. Andersen, A. R., Jensen, J. K., Christiansen, J. S., Deckert, T. ibid.
suppl. 209, p. 1.
p. 15. 1977,
1. Cook, S. D., Dowling, P. C. Lancet, 1977, i, 980. 2. Poskanzer, D. C., Prenney, L. B., Sheridan, J. L. ibid. p. 1204. 3. Bauer, H. J., Wikström, J. ibid. 1977, ii, 1029. 4. Visscher, B., Detels, R. ibid. p. 658. 5. Craelius, W., Newby, N. A. ibid. p. 565. 6. Klauber, M. R., Lyon, J. L. ibid. p. 454. 7. Cook, S. D., Natelson, B. H., Levin, B. E., Chavis, P. S., Dowling, P. C. Ann. Neurol. (in the press). 8. Jotkowitz, S. J. Am. med. Ass. 1977, 238, 854. 9. Innes, J. R. M., Saunders, L Z. Comparative Neuropathology. New York, 1962. 10. McGrath, J. T. Neurological Examination of the Dog. Philadelphia, 1960. 11. Wisniewski, H., Raine, C. S., Kay, W. J. Lab. Invest. 1972, 26, 589. 12. Adams, J. M., Brown, W. J., Snow, H. D., Lincoln, S. D., Sears, A. W., Barenfus, M., Holliday, T. A., Cremer, N. E., Lennette, E. H. Vet. Path.
1975, 12, 220. 13. Appel, M. J. G., Gillespie, J. H. Canine Distemper Virus. Austria, 1972. 14. Chan, W. W.-C. Lancet, 1977, i, 487. 15. Acheson, E. D. Multiple Sclerosis: a Reappraisal. Edinburgh, 1972. 16. Cook, S. D. Vet. Rec. 1977, 101, 314. 17. Kurtzke, J. F., Hyllested, K. Trans. Am. Neurol. Ass. 1975, 100, 213.
606 cases could be the effect of a single cause introduced into the Faeroes at a single time before 1944. A high percentage of inhabitants of the Orkney and Shetland Islands have been exposed to dogs (personal communication, Dr David Poskanzer) and veterinarians inform us that canine distemper is endemic on these islands and may not be controlled; only 5% of dogs receive a primary vaccination and less than 1% receive a booster. In contrast, the chief veterinary officer of the Faeroe Islands, Dr D. J. Baerentsen, tells us that there has been no canine distemper on the Faeroes since 1956, presumably as a result of a strict control on the import of dogs, and consequently dogs are not vaccinated against the disease. Bxrentsen has examined the records of his predecessor, Mr C. J. Bech, and found that canine distemper had not been recorded in the islands before 1939 (restrictions apparently operated on dog influx even at that time). However, after the arrival of British troops in the early 1940s there was an epidemic of canine distemper in the Faeroes, apparently introduced by dogs brought in by British officers. Three-quarters of all dogs in the Faeroes may have died and Bech remarked in his records that "nervous complications were marked in the affected dogs with both convulsive seizures and encephalitic
BONE-MARROW INFILTRATION AND CLINICAL STAGING IN C.L.L.
nodular and diffuse bone-marrow lymphocytic infiltration6) and the clinical,stage assessed as proposed by the Committee of the Chronic Leukemia-Myeloma Task Force’ (see table). Our findings confirm the prognostic value of the marrow infiltration pattern, even if biopsy is done some time after diagnosis or the start of chemotherapy. ANTONINO CARBONE ARMANDO SANTORO Istituto Nazionale per lo Studio SILVANA PILOTTI e la Cura dei Tumori, 20133 Milan, Italy FRANCO RILKE -
signs". Thus two diseases, apparently non-existent before the war and since 1960 (except for 1 case of M.S. in 1961 and 1 in 1970), occurred in epidemics in the Faeroe Islands between 1940 and 1960, canine distemper infection of dogs preceding M.S. in man. Commenting on this epidemic of M.S. in the Faeroes Kurtzke and Hyllested postulated that "M.S. was transmitted to the Faeroese by the British forces (and /or their impedimenta)"." Dogs with distemper seem to have been among these impedimenta and, coupled with the epidemiological data obtained from individual M.S. patients, these findings strengthen the possibility that c.D.v. may be at least one of the factors involved in the aetiology of M.S. It should be stressed, however, that the association between c.D.v. and M.S. described here is only a temporal one, and much more work is required before any more direct link can be established. Veterans Administration Hospital, East Orange, and Department of Neurosciences, New Jersey Medical School, Newark, New Jersey, U.S.A.
S. D. COOK P. C. DOWLING
Division of Virology, National Institute for Medical Research, London NW7
W. C. RUSSELL
BONE-MARROW PATTERNS AND CLINICAL STAGING IN CHRONIC LYMPHOCYTIC LEUKÆMIA
SIR,-Hernandez-Nieto et al.’ showed in chronic lymphocytic leukaemia (C.L.L.) a significant correlation between the histological picture of bone-marrow lymphocytic infiltration evaluated by Rywlin,2and the clinical stage classified according to Rai et al.,3 and stressed the prognostic usefulness of bone biopsies. Charron et a1.4 also found a relationship between the type of marrow infiltration and the clinical stage evaluated by Rai’s modified classification.5 We have studied 30 patients with c.L.L. (median interval between diagnosis and bone biopsy 13 months, range 0.5 to 213 months) of whom 13 were under treatment at the time of biopsy. We found a statistically significant correlation (P
gestion !
! ,.
S. LAUWERS M. DE BOECK J. P. BUTZLER
Department of Microbiology, St Pierre Hospital, 1000 Brussels, Belgium
SMOKING AND DIABETIC NEPHROPATHY
Sm,—Little is known about factors influencing the course and development of diabetic microangiopathy. One report of a possible relation between cigarette smoking and proliferative retinopathy’ is not wholly convincing because smoking and non-smoking diabetics were not sufficiently matched for type and duration of diabetes. Nephropathy, one manifestation of diabetic microangiopathy, is the most frequent cause of death in young diaPREVALENCE OF NEPHROPATHY IN SMOKING AND NON-SMOKING PATIENTS WITH
INSULIN-DEPENDENT, JUVENILE-ONSET DIABETES
significantly higher frequency of diabetic nephropathy found among cigarette smokers (table). The prevalence of hypertension did not vary with smoking habits. Since nephropathy is the most serious complication in longterm juvenile diabetes2.3 and since cigarette smoking should be avoided for other reasons it would be of interest if other groups were to confirm this observation. J. SANDAHL CHRISTIANSEN Steno Memorial Hospital, DK-2820 Gentofte, Copenhagen, Denmark J. NERUP A
was
MULTIPLE SCLEROSIS AND CANINE DISTEMPER
SiR,—An epidemiological study of familial multiple sclerosis (M.S.) suggesting a possible association between dogs and rt.s.l was criticised in your correspondence columns last year.2-6 Poskanzer et al.2 found no association between house pets and M.s. in the Orkney and Shetland Islands, although they noted that a high proportion of both control and M.s. groups were exposed to house pets. Epidemiological studies have also been done in the United States, the results suggesting an increased exposure of some M.s. patients to dogs with a distemper-likeillness before clinical onset of M.S.l,7,8 Bauer and Wikstrom3 in West Germany did not find a relationship between dogs and M.S., but again they did find more dogs thought to have distemper in the ns.s. group.’ Canine distemper virus (C.D.V.) is a paramyxovirus which can produce a neurological demyelinating disease in dogs with many similarities to M.s.9-13 Clinically distemper may be more common in cold weather,13 and these environmental conditions might increase contact between infectious dogs and man. Many of the characteristics of c.D.v. and its canine vector, in close association with man, could account for some of the geographical and cultural peculiarities seen in M.s. distribution.7,14,15 Preliminary serological studies have shown raised serum antibodies to C.D.v. in M.s. patients, as measured by immunonuorescence (a technique which, however, may not distinguish c.D.v. from other paramyxoviruses, such as measles virus).’ In view of these findings it seems possible that the development of M.s. may involve transmission of a virus from animal to man and that c..v. is a prime candidate.1.7.8,16 With this hypothesis in mind, we have been examining the apparently anomalous prevalence of M.s. in the Orkney and Shetland Islands as compared with the Faeroe Islands, particularly with respect to disease patterns of
distemper.
-
Orkney and Shetland the prevalence of M.s. is as high as 300 per 100 000 population,2 whereas in the Faeroe Islands (population 40 000) some 300 km to the north-west, no cases of M.s. were recorded from 1929 to 1943 and only 2 cases between 1960 and 1974 in the Faeroese" (who have many cultural and other similarities to the inhabitants of the Orkney and Shetland Islands). However, from 1944 to 1960 the Faeroe Islands experienced an "epidemic" of M.s. with 18 definite cases Kurtzke and Hyllesred17 suggested that these In
+C=Daily cigarette smoking for more than one year. -C=Never smoked cigarettes or cigarette smoking less than one year. tChi-square test. ’
so we have looked for a link between cigarette smokand diabetic nephropathy. The prevalence of diabetic ing nephropathy in a consecutive series of 238 insulin-dependent, juvenile-onset (before age 31) diabetics was related to current and previous smoking habits and to duration of disease. Diabetic nephropathy was defined as a raised serum-creatinine and/or persistent proteinuria without a history or clinical signs of non-diabetic renal disease. Cigarette smokers were defined as patients who had smoked at least 10 cigarettes a day for more than a year.
betics,2.3
4. Butzler,
J. P., Dekegel, D., Hubrechts, J. M., Lauwers, S., Zissis, G. Paper presented at joint meeting of British Society for the Study of Infection and the Infectious Diseases Society of America, held in Glasgow in 1976. 1. Pantkau, M. E., Boys, T. A. S., Winship, B., Grace, M. Diabetes, 1977, 26,
46. 2. Deckert, T., Poulsen, J. E., Larsen, M. Acta endocr. 1976, suppl. 203, 3. Andersen, A. R., Jensen, J. K., Christiansen, J. S., Deckert, T. ibid.
suppl. 209, p. 1.
p. 15. 1977,
1. Cook, S. D., Dowling, P. C. Lancet, 1977, i, 980. 2. Poskanzer, D. C., Prenney, L. B., Sheridan, J. L. ibid. p. 1204. 3. Bauer, H. J., Wikström, J. ibid. 1977, ii, 1029. 4. Visscher, B., Detels, R. ibid. p. 658. 5. Craelius, W., Newby, N. A. ibid. p. 565. 6. Klauber, M. R., Lyon, J. L. ibid. p. 454. 7. Cook, S. D., Natelson, B. H., Levin, B. E., Chavis, P. S., Dowling, P. C. Ann. Neurol. (in the press). 8. Jotkowitz, S. J. Am. med. Ass. 1977, 238, 854. 9. Innes, J. R. M., Saunders, L Z. Comparative Neuropathology. New York, 1962. 10. McGrath, J. T. Neurological Examination of the Dog. Philadelphia, 1960. 11. Wisniewski, H., Raine, C. S., Kay, W. J. Lab. Invest. 1972, 26, 589. 12. Adams, J. M., Brown, W. J., Snow, H. D., Lincoln, S. D., Sears, A. W., Barenfus, M., Holliday, T. A., Cremer, N. E., Lennette, E. H. Vet. Path.
1975, 12, 220. 13. Appel, M. J. G., Gillespie, J. H. Canine Distemper Virus. Austria, 1972. 14. Chan, W. W.-C. Lancet, 1977, i, 487. 15. Acheson, E. D. Multiple Sclerosis: a Reappraisal. Edinburgh, 1972. 16. Cook, S. D. Vet. Rec. 1977, 101, 314. 17. Kurtzke, J. F., Hyllested, K. Trans. Am. Neurol. Ass. 1975, 100, 213.
606 cases could be the effect of a single cause introduced into the Faeroes at a single time before 1944. A high percentage of inhabitants of the Orkney and Shetland Islands have been exposed to dogs (personal communication, Dr David Poskanzer) and veterinarians inform us that canine distemper is endemic on these islands and may not be controlled; only 5% of dogs receive a primary vaccination and less than 1% receive a booster. In contrast, the chief veterinary officer of the Faeroe Islands, Dr D. J. Baerentsen, tells us that there has been no canine distemper on the Faeroes since 1956, presumably as a result of a strict control on the import of dogs, and consequently dogs are not vaccinated against the disease. Bxrentsen has examined the records of his predecessor, Mr C. J. Bech, and found that canine distemper had not been recorded in the islands before 1939 (restrictions apparently operated on dog influx even at that time). However, after the arrival of British troops in the early 1940s there was an epidemic of canine distemper in the Faeroes, apparently introduced by dogs brought in by British officers. Three-quarters of all dogs in the Faeroes may have died and Bech remarked in his records that "nervous complications were marked in the affected dogs with both convulsive seizures and encephalitic
BONE-MARROW INFILTRATION AND CLINICAL STAGING IN C.L.L.
nodular and diffuse bone-marrow lymphocytic infiltration6) and the clinical,stage assessed as proposed by the Committee of the Chronic Leukemia-Myeloma Task Force’ (see table). Our findings confirm the prognostic value of the marrow infiltration pattern, even if biopsy is done some time after diagnosis or the start of chemotherapy. ANTONINO CARBONE ARMANDO SANTORO Istituto Nazionale per lo Studio SILVANA PILOTTI e la Cura dei Tumori, 20133 Milan, Italy FRANCO RILKE -
signs". Thus two diseases, apparently non-existent before the war and since 1960 (except for 1 case of M.S. in 1961 and 1 in 1970), occurred in epidemics in the Faeroe Islands between 1940 and 1960, canine distemper infection of dogs preceding M.S. in man. Commenting on this epidemic of M.S. in the Faeroes Kurtzke and Hyllested postulated that "M.S. was transmitted to the Faeroese by the British forces (and /or their impedimenta)"." Dogs with distemper seem to have been among these impedimenta and, coupled with the epidemiological data obtained from individual M.S. patients, these findings strengthen the possibility that c.D.v. may be at least one of the factors involved in the aetiology of M.S. It should be stressed, however, that the association between c.D.v. and M.S. described here is only a temporal one, and much more work is required before any more direct link can be established. Veterans Administration Hospital, East Orange, and Department of Neurosciences, New Jersey Medical School, Newark, New Jersey, U.S.A.
S. D. COOK P. C. DOWLING
Division of Virology, National Institute for Medical Research, London NW7
W. C. RUSSELL
BONE-MARROW PATTERNS AND CLINICAL STAGING IN CHRONIC LYMPHOCYTIC LEUKÆMIA
SIR,-Hernandez-Nieto et al.’ showed in chronic lymphocytic leukaemia (C.L.L.) a significant correlation between the histological picture of bone-marrow lymphocytic infiltration evaluated by Rywlin,2and the clinical stage classified according to Rai et al.,3 and stressed the prognostic usefulness of bone biopsies. Charron et a1.4 also found a relationship between the type of marrow infiltration and the clinical stage evaluated by Rai’s modified classification.5 We have studied 30 patients with c.L.L. (median interval between diagnosis and bone biopsy 13 months, range 0.5 to 213 months) of whom 13 were under treatment at the time of biopsy. We found a statistically significant correlation (P
