- Email: [email protected]
Healing of cavity wounds with sugar
571
His Crohn’s disease activity index (CDAI)4 was 177 and systemic indices of inflammation were raised (erythrocyte sedimentation rate [ESR] 67 mm/h, orosomucoids 2-7 g/l, C-reactive protein [CRP] 88-6 mg/1). He improved rapidly, had no pain, and stools were normal for three weeks after anti-CD4 treatment. ESR fell to 45 mm/h, orosomucoids to 1 -8 g/l, and CRP to 38 mg/1. After four weeks, he had a mild relapse, which responded to a higher dose of
prednisolone (20 mg). Patients 2 and 3 both had a longstanding history (6 and 9 years, respectively) of severe left-sided ulcerative colitis, with multiple relapses despite appropriate maintenance therapy. Both had had chronically active disease for more than six months. Moderate improvement was only seen at more than 30 mg prednisolone per day. Patient 2 responded to anti-CD4 treatment clinically, and by a transient reduction of CRP, but relapsed after one month. Patient 3, however, has had complete clinical, endoscopic, and biochemical remission (figure) for more than five months. In inflammatory bowel disease, T cells in the lamina propria may represent an unusual stage of differentiation, and they seem to be hyperresponsive;s this might contribute to local inflammation. In our study, treatment with MAX.16H5 led to a substantial and immediate depletion of CD4 cells from the circulation in all patients as has been shown in rheumatoid arthritis.3 Anti-CD4 treatment also induced striking immunomodulation, as shown by reduced lymphocyte proliferation on stimulation with various mitogens and recall antigens. A transient reduction of the density of CD4 molecules on the surface of helper T cells was also seen. Whether or not these observations are part of the mechanism of action of this therapy is unknown. It is noteworthy that CD4 depletion could be detected to the same extent and with the same kinetics in both responders and non-responders to anti-CD4 therapy who had rheumatoid arthritis.3 None of our patients had side-effects from antibody treatment. Our findings demonstrate that such therapy can be successful in inflammatory bowel disease when conventional drugs have failed. A single cycle of anti-CD4 at the doses we used is not sufficient to persistently suppress disease activity in all patients. Prolonged or repeated courses of antibody therapy or in combination with immunosuppressive drugs should be considered. The Max-Planck-Research Unit for Rheumatology/Immunology is funded by the German Ministry for Research and Technology (BMFT). Medical Clinic, and Institute of Clinical Immunology, University of Rostock, D-2500 Rostock, Germany
S. MURPHY
M. SEYFARTH
N. J. BEECHING S. J. ROGERSON
W. E. FLEIG F. EMMRICH
Selby WS, Janossy G, Mason DY, Jewell DP. Expression of HLA-DR antigens by colonic epithelium in inflammatory bowel disease. Clin Exp Immunol 1983; 53: 614-18.
Raedler A, Fraenkel S, Klose G, Thiele HG. Elevated numbers of peripheral T cell in inflammatory bowel diseases displaying T9 antigen and Fc alpha receptors. Clin Exp Immunol 1985; 60: 518-24. 3. Homeff G, Burmester GR, Emmrich F, Kalden JR. Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody. Arthritis Rheumatism 1991; 34:
2.
129-40. 4. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s disease activity index. Gastroenterology 1976; 70: 439-44. 5. Zeitz M, Quinn TC, Graeff AS, James SP. Mucosal T cells provide helper function but do not proliferate when stimulated by specific antigen in Lymphogranuloma venerum proctitis in nonhuman primates. Gastroenterology 1988; 94: 353-66.
Pancreatitis associated with Salmonella enteritis SIR,-After the letter from Dr Renner and colleagues (June 29, 1611), who suggest that pancreatitis is common in salmonellosis,
describe our own experience. We have recently completed a retrospective review of all 343 adults admitted to our hospital with non-typhoidal salmonella gastroenteritis between January, 1982,
we
and
June,
1989. The
commonest
There was no difference (Kruskal-Wallis) in the mean amylase activities among the salmonella group compared with the campylobacter group, or between the salmonella and campylobacter groups combined compared with all other pathogens. Slightly raised amylase activites were found in only 1 patient with salmonella (110 IU/1) and in 3 with no pathogen isolated (98, 112, and 135 IU/1). None of the 5 bacteraemic salmonella patients had a raised serum amylase. Our findings contrast with the 62% of patients with salmonella reported by Renner et al and the high frequency of campylobacter isolates reported by others2 all of which have been associated with raised amylase and lipase activities. Although cases of severe pancreatitis associated with campylobacter infections have been reported,3,4 this complication appears to be rare. We agree that an infective cause should be thought of in a patient with abdominal pain, diarrhoea, and hyperamylasaemia, but we question the clinical importance of hyperamylasaemia in the majority of patients with infective gastroenteritis.
Regional Infectious Disease Unit, Fazakerley Hospital, Liverpool L9 7AL, UK
University of Erlangen-Nurnherg, University of Erlangen, D-8520 Erlangen, Germany
p
158 patients who had blood cultures taken were bacteraemic. Complications were noted, but serum amylase estimations and abdominal ultrasonography were rarely completed and were not systematically recorded in our review. None of the 343 patients had clinically apparent pancreatitis. Since July, 1989, we have prospectively studied adults admitted to our unit with acute gastroenteritis. Patients thought to have toxin-mediated food poisoning at the time of admission were excluded from the study protocol, which includes at least two blood cultures and estimation of serum amylase on admission, but does not routinely include sonography. The distribution of causative pathogens is representative of patients admitted to our unit with gastroenteritis1 and the commonest salmonella isolates were S enteritidis (465%) and S typhimurium (172%). None of the patients had clinically apparent pancreatitis. Serum amylase activities (normal range 10-96 IU/1) that were available for 147 of 171 patients are summarised below:
J. EMMRICH
Medical Clinic I, and Clinical Research Unit for Rheumatology/Immunology, Institute for Immunology,
1.
typhimuriwn (445%) and S enteritidis (276%); 27 (17’1 1 %) of the
isolates
were
Salmonella
A. D. HARRIES
1. Felton M, Harries AD, Beeching NJ, Rogerson SJ, Nye FJ. Acute gastroenteritis: the need to remember alternative diagnoses. Postgrad Med J 1990; 66: 1037-39. 2. Pitkanen T, Pönka A, Pettersson T, Kosunen TU. Campylobacter enteritis in 188 hospitalized patients. Arch Intern Med 1983; 143: 215-19. 3. Gallagher P, Chadwick P, Jones DM, Turner L. Acute pancreatitis associated with campylobacter infection. Br J Surg 1981; 68: 383. 4. de Bois MHW, Shoemaker MC, Van der Werf SDJ, Puylaert JBCM. Pancreatitis
associated with Campylobacter jejuni infection: Med J 1989; 298: 1004.
diagnosis by ultrasonography.
Br
Healing of cavity wounds with sugar SiR,—Your April 27 editorial discusses the use of sugar paste as formulated by us. We were surprised by Professor Parish and Professor Witkowski’s (June 1, p 1355) dismissal of the use of sugar as a treatment for the healing wound. The safe and effective application of ordinary granulated sugar to infected wounds has been recorded previously in The Lancet.1,2 We have formulated caster sugar (fine granular sucrose) and icing sugar (powdered sucrose) with polyethylene glycol 400 and hydrogen peroxide into thick and thin pastes. We have shown these pastes to be non-toxic to healing wounds in a controlled trial in the domestic pig.4 The effects of sugar paste on water activity and bacterial growth in vitro have been investigatedWithin wounds, these sugar pastes reduce the available water and this inhibits bacterial growth; however, they still allow granulation tissue to form and
572
to take place at a rate similar to that for control wounds that are kept moist and covered with ’Opsite’ plastic film.4 We have found that packing cavity wounds, such as infected malodorous bed sores (decubitus ulcers), with thick sugar paste has been especially helpful. Not only does the foul odour of anaerobic bacterial growth disappear after several days but necrotic tissue is safely debrided. Regular packing twice daily, with bandages to hold the sugar paste in place, has led to considerable success in healing such bed sores in bed-bound semi-paralytic patients. When granulation tissue is well established, however, and the wound is shrinking, application of sugar paste will cause bleeding and it should be replaced with an alginate, hydrogel, or hydrocolloid
epithelialisation
dressing, as appropriate. Thin sugar paste can be irrigated repeatedly into abscess cavities via large bore catheters instead of packing with ribbon gauze and antiseptics, which delays healing and can be very painful. Furthermore, gauze becomes enmeshed with the developing granulation tissue, which is torn away when the dressing is removed. Dextranomer isomer beads (’Debrisan’) cannot be irrigated into wounds in this way, and they cost more than sugar pastes. Wolfson Centre, Level 5, Glasgow G4 0NA, UK
D. V. SEAL
Department of Pharmacy, Northwick Park Hospital,
K. MIDDLETON
Harrow
1. Chirife J, Scarmatto G, Herszage L. Scientific basis for the use of granulated sugar in the treatment of infected wounds. Lancet 1982; i: 560-61. 2. Trouillet JL, Chastre J, Fagon JY, Pierre J, Domart Y, Gibert C. Use of granulated sugar in treatment of open mediastinitis after cardiac surgery. Lancet 1985; ii: 180-84. 3. Middleton K, Seal DV. Sugar as an aid to wound healing. Pharm J 1985; 235: 757-58. 4. Archer HG, Barnett S, Irving S, Middleton KR, Seal DV. A controlled model of moist wound healing: comparison between semi-permeable film, antiseptics and sugar paste. J Exp Pathol 1990; 71: 155-70. 5. Ambrose U, Middleton K, Seal DV. In vitro studies of water activity and bacterial growth inhibition of sucrose-polyethylene glycol 400-hydrogen peroxide and xylose-polyethylene glycol 400-hydrogen peroxide pastes used to treat infected wounds. Antimicrob Agents Chemother (in press).
Adult T-cell leukaemia and HTLV-I-associated myelopathy in a
family
SIR,-Adult T-cell leukaemia (ATL) and HTLV-1-associated myelopathy tropical spastic paraparesis (HAM/TSP) are known to be caused by the same virus, namely human T-lymphotropic virus type I (HTLV-1).’ How HTLV-1 can cause two different diseases has, until recently, remained unclear. Sonoda et al have suggested that ATL and HAM/TSP are exclusive because of their different HLA haplotypesAlthough their hypothesis is attractive, reports of an ATL patient with HAM/TSP3 and a familial case of both ATL and HAM/TSP4 suggest that it is not possible to explain susceptibility to ATL and HAM/TSP by differences in HLA
haplotypes alone. We now report the first familial cases (figure) of ATL and HAM/TSP in which all HLA haplotypes were analysed:
A 70-year-old woman (patient 2) with cervical lymphadenopathy diagnosed as having malignant lymphoma, diffuse mixed-cell type. Her peripheral blood examination showed abnormal lymphocytes (9% of white cells), and bone marrow puncture revealed an infiltration of abnormal lymphocytes. Her HTLV-I antibody titre was 1024 in serum and 64 in cerebrospinal fluid as measured by particle agglutination. Surface phenotypes of lymphoma cells were CD3 +,CD4 +, and CD8 -. Monoclonal integration of HTLV-I proviral DNA into lymphoma cells was detected by Southern blotting. A diagnosis of lymphoma-type ATL was made. A 36-year-old woman, a daughter of patient 2 (patient 8) noticed paraesthesia in the soles of her feet at age 18. A gait disturbance developed and she needed assistance in walking by age 21. She had urinary incontinence from the age of 25. Physical examination revealed lower limb paraparesis with mild muscle atrophy and moderate sensory deficits. Deep-tendon reflexes were increased in the upper limbs and slightly decreased in the lower limbs. Pathological reflexes were absent. The HTLV-1 antibody titre was greater than 8192 in serum and 128 in cerebrospinal fluid. She was diagnosed as having HAM/TSP according to WHO criteria. There were no differences in haplotypes between these two patients. Haplotypes in our patient with lymphoma-type ATL were similar to the "HAM-associated" haplotypes described by Usuku et al,5 but were clearly different from the "ATL-associated" haplotypes. Although some workers suggest that HTLV-1 carriers may get two different diseases because of their different immunological responses to HTLV-1, our data show that ATL and HAM/TSP can develop in individuals with the "HAM-associated" haplotypes. These findings suggest that development of ATL and HAM/TSP in HTLV-I carriers, especially leukaemogenesis of CD4 lymphocytes in ATL, is not controlled by HLA-linked genes alone. was
The Second Department of Internal Medicine, Faculty of Medicine,
Kagoshima University, Kagoshima, Japan
KIMIHARU UOZUMI MASAHITO IWAHASHI HIROICHIROH UEDA MAKI OTSUKA KAZUAKI ISHIBASHI SHUICHI HANADA TERUKATSU ARIMA
1. Yoshida
M, Osame M, Usuku K, Matsumoto M, Igatu A. Viruses detected in HTLV-I-associated myelopathy and adult T-cell leukaemia are identical on DNA blotting. Lancet 1987; i. 1085-86. 2. Sonoda S. Genetic and immunologic determinants of HTLV-I-associated diseases. In: Blattner WA, ed. Human retrovirology: HTLV. New York: Raven Press, 1990. 315-26.
Kawai H, et al. HTLV-I-associated myelopathy with adult T-cell leukemia. Neurology 1989; 39: 1129-31. 4. Shoji H, et al. HTLV-I-associated myelopathy and adult T-cell leukemia cases in a family. Eur Neurol 1989; 29: 33-35. 5. Usuku K, et al. HLA haplotype-linked high immune responsiveness against HTLV-I in HTLV-I-associated myelopathy: comparison with adult T-cell leukemia/ lymphoma. Ann Neurol 1988; 23 (suppl). s143-s150. 3.
HCV in saliva of chronic hepatitis having dental treatment
patients
SIR,-It is well known that human saliva occasionally contains viral agents, including the hepatitis viruses, cytomegalovirus, and Epstein-Barr virus. Reports have indicated that hepatitis C virus (HCV) is detectable in saliva by polymerase chain reaction (PCR), suggesting a possible source of HCV various
Family pedigree. Circled numbers correspond to the table; uncircled numbers refer to age. Shaded squares (men) and circles (women) are patients who were diagnosed as having HAM/TSP both clinically and by HTLV-I serology.
infection.1,2 During treatment or after remission of hepatitis, patients sometimes receive dental treatment. We have examined the
His Crohn’s disease activity index (CDAI)4 was 177 and systemic indices of inflammation were raised (erythrocyte sedimentation rate [ESR] 67 mm/h, orosomucoids 2-7 g/l, C-reactive protein [CRP] 88-6 mg/1). He improved rapidly, had no pain, and stools were normal for three weeks after anti-CD4 treatment. ESR fell to 45 mm/h, orosomucoids to 1 -8 g/l, and CRP to 38 mg/1. After four weeks, he had a mild relapse, which responded to a higher dose of
prednisolone (20 mg). Patients 2 and 3 both had a longstanding history (6 and 9 years, respectively) of severe left-sided ulcerative colitis, with multiple relapses despite appropriate maintenance therapy. Both had had chronically active disease for more than six months. Moderate improvement was only seen at more than 30 mg prednisolone per day. Patient 2 responded to anti-CD4 treatment clinically, and by a transient reduction of CRP, but relapsed after one month. Patient 3, however, has had complete clinical, endoscopic, and biochemical remission (figure) for more than five months. In inflammatory bowel disease, T cells in the lamina propria may represent an unusual stage of differentiation, and they seem to be hyperresponsive;s this might contribute to local inflammation. In our study, treatment with MAX.16H5 led to a substantial and immediate depletion of CD4 cells from the circulation in all patients as has been shown in rheumatoid arthritis.3 Anti-CD4 treatment also induced striking immunomodulation, as shown by reduced lymphocyte proliferation on stimulation with various mitogens and recall antigens. A transient reduction of the density of CD4 molecules on the surface of helper T cells was also seen. Whether or not these observations are part of the mechanism of action of this therapy is unknown. It is noteworthy that CD4 depletion could be detected to the same extent and with the same kinetics in both responders and non-responders to anti-CD4 therapy who had rheumatoid arthritis.3 None of our patients had side-effects from antibody treatment. Our findings demonstrate that such therapy can be successful in inflammatory bowel disease when conventional drugs have failed. A single cycle of anti-CD4 at the doses we used is not sufficient to persistently suppress disease activity in all patients. Prolonged or repeated courses of antibody therapy or in combination with immunosuppressive drugs should be considered. The Max-Planck-Research Unit for Rheumatology/Immunology is funded by the German Ministry for Research and Technology (BMFT). Medical Clinic, and Institute of Clinical Immunology, University of Rostock, D-2500 Rostock, Germany
S. MURPHY
M. SEYFARTH
N. J. BEECHING S. J. ROGERSON
W. E. FLEIG F. EMMRICH
Selby WS, Janossy G, Mason DY, Jewell DP. Expression of HLA-DR antigens by colonic epithelium in inflammatory bowel disease. Clin Exp Immunol 1983; 53: 614-18.
Raedler A, Fraenkel S, Klose G, Thiele HG. Elevated numbers of peripheral T cell in inflammatory bowel diseases displaying T9 antigen and Fc alpha receptors. Clin Exp Immunol 1985; 60: 518-24. 3. Homeff G, Burmester GR, Emmrich F, Kalden JR. Treatment of rheumatoid arthritis with an anti-CD4 monoclonal antibody. Arthritis Rheumatism 1991; 34:
2.
129-40. 4. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s disease activity index. Gastroenterology 1976; 70: 439-44. 5. Zeitz M, Quinn TC, Graeff AS, James SP. Mucosal T cells provide helper function but do not proliferate when stimulated by specific antigen in Lymphogranuloma venerum proctitis in nonhuman primates. Gastroenterology 1988; 94: 353-66.
Pancreatitis associated with Salmonella enteritis SIR,-After the letter from Dr Renner and colleagues (June 29, 1611), who suggest that pancreatitis is common in salmonellosis,
describe our own experience. We have recently completed a retrospective review of all 343 adults admitted to our hospital with non-typhoidal salmonella gastroenteritis between January, 1982,
we
and
June,
1989. The
commonest
There was no difference (Kruskal-Wallis) in the mean amylase activities among the salmonella group compared with the campylobacter group, or between the salmonella and campylobacter groups combined compared with all other pathogens. Slightly raised amylase activites were found in only 1 patient with salmonella (110 IU/1) and in 3 with no pathogen isolated (98, 112, and 135 IU/1). None of the 5 bacteraemic salmonella patients had a raised serum amylase. Our findings contrast with the 62% of patients with salmonella reported by Renner et al and the high frequency of campylobacter isolates reported by others2 all of which have been associated with raised amylase and lipase activities. Although cases of severe pancreatitis associated with campylobacter infections have been reported,3,4 this complication appears to be rare. We agree that an infective cause should be thought of in a patient with abdominal pain, diarrhoea, and hyperamylasaemia, but we question the clinical importance of hyperamylasaemia in the majority of patients with infective gastroenteritis.
Regional Infectious Disease Unit, Fazakerley Hospital, Liverpool L9 7AL, UK
University of Erlangen-Nurnherg, University of Erlangen, D-8520 Erlangen, Germany
p
158 patients who had blood cultures taken were bacteraemic. Complications were noted, but serum amylase estimations and abdominal ultrasonography were rarely completed and were not systematically recorded in our review. None of the 343 patients had clinically apparent pancreatitis. Since July, 1989, we have prospectively studied adults admitted to our unit with acute gastroenteritis. Patients thought to have toxin-mediated food poisoning at the time of admission were excluded from the study protocol, which includes at least two blood cultures and estimation of serum amylase on admission, but does not routinely include sonography. The distribution of causative pathogens is representative of patients admitted to our unit with gastroenteritis1 and the commonest salmonella isolates were S enteritidis (465%) and S typhimurium (172%). None of the patients had clinically apparent pancreatitis. Serum amylase activities (normal range 10-96 IU/1) that were available for 147 of 171 patients are summarised below:
J. EMMRICH
Medical Clinic I, and Clinical Research Unit for Rheumatology/Immunology, Institute for Immunology,
1.
typhimuriwn (445%) and S enteritidis (276%); 27 (17’1 1 %) of the
isolates
were
Salmonella
A. D. HARRIES
1. Felton M, Harries AD, Beeching NJ, Rogerson SJ, Nye FJ. Acute gastroenteritis: the need to remember alternative diagnoses. Postgrad Med J 1990; 66: 1037-39. 2. Pitkanen T, Pönka A, Pettersson T, Kosunen TU. Campylobacter enteritis in 188 hospitalized patients. Arch Intern Med 1983; 143: 215-19. 3. Gallagher P, Chadwick P, Jones DM, Turner L. Acute pancreatitis associated with campylobacter infection. Br J Surg 1981; 68: 383. 4. de Bois MHW, Shoemaker MC, Van der Werf SDJ, Puylaert JBCM. Pancreatitis
associated with Campylobacter jejuni infection: Med J 1989; 298: 1004.
diagnosis by ultrasonography.
Br
Healing of cavity wounds with sugar SiR,—Your April 27 editorial discusses the use of sugar paste as formulated by us. We were surprised by Professor Parish and Professor Witkowski’s (June 1, p 1355) dismissal of the use of sugar as a treatment for the healing wound. The safe and effective application of ordinary granulated sugar to infected wounds has been recorded previously in The Lancet.1,2 We have formulated caster sugar (fine granular sucrose) and icing sugar (powdered sucrose) with polyethylene glycol 400 and hydrogen peroxide into thick and thin pastes. We have shown these pastes to be non-toxic to healing wounds in a controlled trial in the domestic pig.4 The effects of sugar paste on water activity and bacterial growth in vitro have been investigatedWithin wounds, these sugar pastes reduce the available water and this inhibits bacterial growth; however, they still allow granulation tissue to form and
572
to take place at a rate similar to that for control wounds that are kept moist and covered with ’Opsite’ plastic film.4 We have found that packing cavity wounds, such as infected malodorous bed sores (decubitus ulcers), with thick sugar paste has been especially helpful. Not only does the foul odour of anaerobic bacterial growth disappear after several days but necrotic tissue is safely debrided. Regular packing twice daily, with bandages to hold the sugar paste in place, has led to considerable success in healing such bed sores in bed-bound semi-paralytic patients. When granulation tissue is well established, however, and the wound is shrinking, application of sugar paste will cause bleeding and it should be replaced with an alginate, hydrogel, or hydrocolloid
epithelialisation
dressing, as appropriate. Thin sugar paste can be irrigated repeatedly into abscess cavities via large bore catheters instead of packing with ribbon gauze and antiseptics, which delays healing and can be very painful. Furthermore, gauze becomes enmeshed with the developing granulation tissue, which is torn away when the dressing is removed. Dextranomer isomer beads (’Debrisan’) cannot be irrigated into wounds in this way, and they cost more than sugar pastes. Wolfson Centre, Level 5, Glasgow G4 0NA, UK
D. V. SEAL
Department of Pharmacy, Northwick Park Hospital,
K. MIDDLETON
Harrow
1. Chirife J, Scarmatto G, Herszage L. Scientific basis for the use of granulated sugar in the treatment of infected wounds. Lancet 1982; i: 560-61. 2. Trouillet JL, Chastre J, Fagon JY, Pierre J, Domart Y, Gibert C. Use of granulated sugar in treatment of open mediastinitis after cardiac surgery. Lancet 1985; ii: 180-84. 3. Middleton K, Seal DV. Sugar as an aid to wound healing. Pharm J 1985; 235: 757-58. 4. Archer HG, Barnett S, Irving S, Middleton KR, Seal DV. A controlled model of moist wound healing: comparison between semi-permeable film, antiseptics and sugar paste. J Exp Pathol 1990; 71: 155-70. 5. Ambrose U, Middleton K, Seal DV. In vitro studies of water activity and bacterial growth inhibition of sucrose-polyethylene glycol 400-hydrogen peroxide and xylose-polyethylene glycol 400-hydrogen peroxide pastes used to treat infected wounds. Antimicrob Agents Chemother (in press).
Adult T-cell leukaemia and HTLV-I-associated myelopathy in a
family
SIR,-Adult T-cell leukaemia (ATL) and HTLV-1-associated myelopathy tropical spastic paraparesis (HAM/TSP) are known to be caused by the same virus, namely human T-lymphotropic virus type I (HTLV-1).’ How HTLV-1 can cause two different diseases has, until recently, remained unclear. Sonoda et al have suggested that ATL and HAM/TSP are exclusive because of their different HLA haplotypesAlthough their hypothesis is attractive, reports of an ATL patient with HAM/TSP3 and a familial case of both ATL and HAM/TSP4 suggest that it is not possible to explain susceptibility to ATL and HAM/TSP by differences in HLA
haplotypes alone. We now report the first familial cases (figure) of ATL and HAM/TSP in which all HLA haplotypes were analysed:
A 70-year-old woman (patient 2) with cervical lymphadenopathy diagnosed as having malignant lymphoma, diffuse mixed-cell type. Her peripheral blood examination showed abnormal lymphocytes (9% of white cells), and bone marrow puncture revealed an infiltration of abnormal lymphocytes. Her HTLV-I antibody titre was 1024 in serum and 64 in cerebrospinal fluid as measured by particle agglutination. Surface phenotypes of lymphoma cells were CD3 +,CD4 +, and CD8 -. Monoclonal integration of HTLV-I proviral DNA into lymphoma cells was detected by Southern blotting. A diagnosis of lymphoma-type ATL was made. A 36-year-old woman, a daughter of patient 2 (patient 8) noticed paraesthesia in the soles of her feet at age 18. A gait disturbance developed and she needed assistance in walking by age 21. She had urinary incontinence from the age of 25. Physical examination revealed lower limb paraparesis with mild muscle atrophy and moderate sensory deficits. Deep-tendon reflexes were increased in the upper limbs and slightly decreased in the lower limbs. Pathological reflexes were absent. The HTLV-1 antibody titre was greater than 8192 in serum and 128 in cerebrospinal fluid. She was diagnosed as having HAM/TSP according to WHO criteria. There were no differences in haplotypes between these two patients. Haplotypes in our patient with lymphoma-type ATL were similar to the "HAM-associated" haplotypes described by Usuku et al,5 but were clearly different from the "ATL-associated" haplotypes. Although some workers suggest that HTLV-1 carriers may get two different diseases because of their different immunological responses to HTLV-1, our data show that ATL and HAM/TSP can develop in individuals with the "HAM-associated" haplotypes. These findings suggest that development of ATL and HAM/TSP in HTLV-I carriers, especially leukaemogenesis of CD4 lymphocytes in ATL, is not controlled by HLA-linked genes alone. was
The Second Department of Internal Medicine, Faculty of Medicine,
Kagoshima University, Kagoshima, Japan
KIMIHARU UOZUMI MASAHITO IWAHASHI HIROICHIROH UEDA MAKI OTSUKA KAZUAKI ISHIBASHI SHUICHI HANADA TERUKATSU ARIMA
1. Yoshida
M, Osame M, Usuku K, Matsumoto M, Igatu A. Viruses detected in HTLV-I-associated myelopathy and adult T-cell leukaemia are identical on DNA blotting. Lancet 1987; i. 1085-86. 2. Sonoda S. Genetic and immunologic determinants of HTLV-I-associated diseases. In: Blattner WA, ed. Human retrovirology: HTLV. New York: Raven Press, 1990. 315-26.
Kawai H, et al. HTLV-I-associated myelopathy with adult T-cell leukemia. Neurology 1989; 39: 1129-31. 4. Shoji H, et al. HTLV-I-associated myelopathy and adult T-cell leukemia cases in a family. Eur Neurol 1989; 29: 33-35. 5. Usuku K, et al. HLA haplotype-linked high immune responsiveness against HTLV-I in HTLV-I-associated myelopathy: comparison with adult T-cell leukemia/ lymphoma. Ann Neurol 1988; 23 (suppl). s143-s150. 3.
HCV in saliva of chronic hepatitis having dental treatment
patients
SIR,-It is well known that human saliva occasionally contains viral agents, including the hepatitis viruses, cytomegalovirus, and Epstein-Barr virus. Reports have indicated that hepatitis C virus (HCV) is detectable in saliva by polymerase chain reaction (PCR), suggesting a possible source of HCV various
Family pedigree. Circled numbers correspond to the table; uncircled numbers refer to age. Shaded squares (men) and circles (women) are patients who were diagnosed as having HAM/TSP both clinically and by HTLV-I serology.
infection.1,2 During treatment or after remission of hepatitis, patients sometimes receive dental treatment. We have examined the