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His Crohn’s disease activity index (CDAI)4 was 177 and systemicindices 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 werenormal 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 fourweeks, he had a mild relapse, which responded to a higher dose ofprednisolone (20 mg).

Patients 2 and 3 both had a longstanding history (6 and 9 years,respectively) of severe left-sided ulcerative colitis, with multiplerelapses despite appropriate maintenance therapy. Both had hadchronically active disease for more than six months. Moderateimprovement was only seen at more than 30 mg prednisolone perday. Patient 2 responded to anti-CD4 treatment clinically, and by atransient reduction of CRP, but relapsed after one month. Patient 3,however, has had complete clinical, endoscopic, and biochemicalremission (figure) for more than five months.

In inflammatory bowel disease, T cells in the lamina propria mayrepresent an unusual stage of differentiation, and they seem to behyperresponsive;s this might contribute to local inflammation. Inour study, treatment with MAX.16H5 led to a substantial andimmediate depletion of CD4 cells from the circulation in all patientsas has been shown in rheumatoid arthritis.3 Anti-CD4 treatmentalso induced striking immunomodulation, as shown by reducedlymphocyte proliferation on stimulation with various mitogens andrecall antigens. A transient reduction of the density of CD4molecules on the surface of helper T cells was also seen. Whether ornot these observations are part of the mechanism of action of this

therapy is unknown. It is noteworthy that CD4 depletion could bedetected to the same extent and with the same kinetics in both

responders and non-responders to anti-CD4 therapy who hadrheumatoid arthritis.3None of our patients had side-effects from antibody treatment.

Our findings demonstrate that such therapy can be successful ininflammatory bowel disease when conventional drugs have failed. Asingle cycle of anti-CD4 at the doses we used is not sufficient topersistently suppress disease activity in all patients. Prolonged orrepeated courses of antibody therapy or in combination withimmunosuppressive drugs should be considered.

The Max-Planck-Research Unit for Rheumatology/Immunology isfunded by the German Ministry for Research and Technology (BMFT).

Medical Clinic,and Institute of Clinical Immunology,

University of Rostock,D-2500 Rostock, Germany

J. EMMRICHM. SEYFARTH

Medical Clinic I, and Clinical ResearchUnit for Rheumatology/Immunology,

Institute for Immunology,University of Erlangen-Nurnherg,University of Erlangen,D-8520 Erlangen, Germany

W. E. FLEIGF. EMMRICH

1. Selby WS, Janossy G, Mason DY, Jewell DP. Expression of HLA-DR antigens bycolonic epithelium in inflammatory bowel disease. Clin Exp Immunol 1983; 53:614-18.

2. Raedler A, Fraenkel S, Klose G, Thiele HG. Elevated numbers of peripheral T cell ininflammatory bowel diseases displaying T9 antigen and Fc alpha receptors. ClinExp Immunol 1985; 60: 518-24.

3. Homeff G, Burmester GR, Emmrich F, Kalden JR. Treatment of rheumatoidarthritis with an anti-CD4 monoclonal antibody. Arthritis Rheumatism 1991; 34:129-40.

4. Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s diseaseactivity index. Gastroenterology 1976; 70: 439-44.

5. Zeitz M, Quinn TC, Graeff AS, James SP. Mucosal T cells provide helper functionbut do not proliferate when stimulated by specific antigen in Lymphogranulomavenerum proctitis in nonhuman primates. Gastroenterology 1988; 94: 353-66.

Pancreatitis associated with Salmonellaenteritis

SIR,-After the letter from Dr Renner and colleagues (June 29,p 1611), who suggest that pancreatitis is common in salmonellosis,we describe our own experience. We have recently completed aretrospective review of all 343 adults admitted to our hospital withnon-typhoidal salmonella gastroenteritis between January, 1982,and June, 1989. The commonest isolates were Salmonella

typhimuriwn (445%) and S enteritidis (276%); 27 (17’1 1 %) of the158 patients who had blood cultures taken were bacteraemic.Complications were noted, but serum amylase estimations andabdominal ultrasonography were rarely completed and were notsystematically recorded in our review. None of the 343 patients hadclinically apparent pancreatitis.

Since July, 1989, we have prospectively studied adults admittedto our unit with acute gastroenteritis. Patients thought to havetoxin-mediated food poisoning at the time of admission wereexcluded from the study protocol, which includes at least two bloodcultures and estimation of serum amylase on admission, but doesnot routinely include sonography. The distribution of causativepathogens is representative of patients admitted to our unit withgastroenteritis1 and the commonest salmonella isolates were Senteritidis (465%) and S typhimurium (172%). None of thepatients had clinically apparent pancreatitis. Serum amylaseactivities (normal range 10-96 IU/1) that were available for 147 of171 patients are summarised below:

There was no difference (Kruskal-Wallis) in the mean amylaseactivities 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 1patient with salmonella (110 IU/1) and in 3 with no pathogenisolated (98, 112, and 135 IU/1). None of the 5 bacteraemicsalmonella 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 campylobacterisolates reported by others2 all of which have been associated withraised amylase and lipase activities. Although cases of severepancreatitis associated with campylobacter infections have beenreported,3,4 this complication appears to be rare. We agree that aninfective cause should be thought of in a patient with abdominalpain, diarrhoea, and hyperamylasaemia, but we question the clinicalimportance of hyperamylasaemia in the majority of patients withinfective gastroenteritis.

Regional Infectious Disease Unit,Fazakerley Hospital,Liverpool L9 7AL, UK

S. MURPHY

N. J. BEECHINGS. J. ROGERSONA. D. HARRIES

1. Felton M, Harries AD, Beeching NJ, Rogerson SJ, Nye FJ. Acute gastroenteritis: theneed to remember alternative diagnoses. Postgrad Med J 1990; 66: 1037-39.

2. Pitkanen T, Pönka A, Pettersson T, Kosunen TU. Campylobacter enteritis in 188hospitalized patients. Arch Intern Med 1983; 143: 215-19.

3. Gallagher P, Chadwick P, Jones DM, Turner L. Acute pancreatitis associated withcampylobacter infection. Br J Surg 1981; 68: 383.

4. de Bois MHW, Shoemaker MC, Van der Werf SDJ, Puylaert JBCM. Pancreatitisassociated with Campylobacter jejuni infection: diagnosis by ultrasonography. BrMed J 1989; 298: 1004.

Healing of cavity wounds with sugarSiR,—Your April 27 editorial discusses the use of sugar paste as

formulated by us. We were surprised by Professor Parish andProfessor Witkowski’s (June 1, p 1355) dismissal of the use of sugaras 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 Wehave formulated caster sugar (fine granular sucrose) and icing sugar(powdered sucrose) with polyethylene glycol 400 and hydrogenperoxide into thick and thin pastes. We have shown these pastes tobe non-toxic to healing wounds in a controlled trial in the domesticpig.4 The effects of sugar paste on water activity and bacterialgrowth in vitro have been investigated Within wounds, these sugarpastes reduce the available water and this inhibits bacterial growth;however, they still allow granulation tissue to form and

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epithelialisation to take place at a rate similar to that for controlwounds that are kept moist and covered with ’Opsite’ plastic film.4We have found that packing cavity wounds, such as infected

malodorous bed sores (decubitus ulcers), with thick sugar paste hasbeen especially helpful. Not only does the foul odour of anaerobicbacterial growth disappear after several days but necrotic tissue issafely debrided. Regular packing twice daily, with bandages to holdthe sugar paste in place, has led to considerable success in healingsuch bed sores in bed-bound semi-paralytic patients. Whengranulation tissue is well established, however, and the wound isshrinking, application of sugar paste will cause bleeding and itshould be replaced with an alginate, hydrogel, or hydrocolloiddressing, as appropriate.Thin sugar paste can be irrigated repeatedly into abscess cavities

via large bore catheters instead of packing with ribbon gauze andantiseptics, which delays healing and can be very painful.Furthermore, gauze becomes enmeshed with the developinggranulation tissue, which is torn away when the dressing isremoved. Dextranomer isomer beads (’Debrisan’) cannot be

irrigated into wounds in this way, and they cost more than sugarpastes.

Wolfson Centre, Level 5,Glasgow G4 0NA, UK D. V. SEAL

Department of Pharmacy,Northwick Park Hospital,Harrow K. MIDDLETON

1. Chirife J, Scarmatto G, Herszage L. Scientific basis for the use of granulated sugar inthe treatment of infected wounds. Lancet 1982; i: 560-61.

2. Trouillet JL, Chastre J, Fagon JY, Pierre J, Domart Y, Gibert C. Use of granulatedsugar 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 sugarpaste. J Exp Pathol 1990; 71: 155-70.

5. Ambrose U, Middleton K, Seal DV. In vitro studies of water activity and bacterialgrowth inhibition of sucrose-polyethylene glycol 400-hydrogen peroxide andxylose-polyethylene glycol 400-hydrogen peroxide pastes used to treat infectedwounds. Antimicrob Agents Chemother (in press).

Adult T-cell leukaemia andHTLV-I-associated myelopathy in a familySIR,-Adult T-cell leukaemia (ATL) and HTLV-1-associated

myelopathy tropical spastic paraparesis (HAM/TSP) are known tobe caused by the same virus, namely human T-lymphotropic virustype I (HTLV-1).’ How HTLV-1 can cause two different diseaseshas, until recently, remained unclear. Sonoda et al have suggestedthat ATL and HAM/TSP are exclusive because of their differentHLA haplotypes Although their hypothesis is attractive, reportsof an ATL patient with HAM/TSP3 and a familial case of bothATL and HAM/TSP4 suggest that it is not possible to explainsusceptibility to ATL and HAM/TSP by differences in HLA

Family pedigree.

Circled numbers correspond to the table; uncircled numbers refer toage. Shaded squares (men) and circles (women) are patients who werediagnosed as having HAM/TSP both clinically and by HTLV-I serology.

haplotypes alone. We now report the first familial cases (figure) ofATL and HAM/TSP in which all HLA haplotypes were analysed:

A 70-year-old woman (patient 2) with cervical lymphadenopathywas diagnosed as having malignant lymphoma, diffuse mixed-celltype. Her peripheral blood examination showed abnormal

lymphocytes (9% of white cells), and bone marrow puncturerevealed an infiltration of abnormal lymphocytes. Her HTLV-Iantibody titre was 1024 in serum and 64 in cerebrospinal fluid asmeasured by particle agglutination. Surface phenotypes of

lymphoma cells were CD3 +, CD4 +, and CD8 -. Monoclonalintegration of HTLV-I proviral DNA into lymphoma cells wasdetected by Southern blotting. A diagnosis of lymphoma-typeATL 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 disturbancedeveloped and she needed assistance in walking by age 21. She hadurinary incontinence from the age of 25. Physical examinationrevealed lower limb paraparesis with mild muscle atrophy andmoderate sensory deficits. Deep-tendon reflexes were increased inthe upper limbs and slightly decreased in the lower limbs.

Pathological reflexes were absent. The HTLV-1 antibody titre wasgreater than 8192 in serum and 128 in cerebrospinal fluid. She wasdiagnosed 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 weresimilar to the "HAM-associated" haplotypes described by Usuku etal,5 but were clearly different from the "ATL-associated"

haplotypes. Although some workers suggest that HTLV-1 carriersmay get two different diseases because of their different

immunological responses to HTLV-1, our data show that ATL andHAM/TSP can develop in individuals with the "HAM-associated"haplotypes. These findings suggest that development of ATL andHAM/TSP in HTLV-I carriers, especially leukaemogenesis ofCD4 lymphocytes in ATL, is not controlled by HLA-linked genesalone.

The Second Department ofInternal Medicine,

Faculty of Medicine,Kagoshima University,Kagoshima, Japan

KIMIHARU UOZUMIMASAHITO IWAHASHIHIROICHIROH UEDAMAKI OTSUKAKAZUAKI ISHIBASHISHUICHI HANADATERUKATSU ARIMA

1. Yoshida M, Osame M, Usuku K, Matsumoto M, Igatu A. Viruses detected inHTLV-I-associated myelopathy and adult T-cell leukaemia are identical on DNAblotting. 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.

3. Kawai H, et al. HTLV-I-associated myelopathy with adult T-cell leukemia. Neurology1989; 39: 1129-31.

4. Shoji H, et al. HTLV-I-associated myelopathy and adult T-cell leukemia cases in afamily. Eur Neurol 1989; 29: 33-35.

5. Usuku K, et al. HLA haplotype-linked high immune responsiveness against HTLV-Iin HTLV-I-associated myelopathy: comparison with adult T-cell leukemia/lymphoma. Ann Neurol 1988; 23 (suppl). s143-s150.

HCV in saliva of chronic hepatitis patientshaving dental treatment

SIR,-It is well known that human saliva occasionally containsvarious viral agents, including the hepatitis viruses,cytomegalovirus, and Epstein-Barr virus. Reports have indicatedthat hepatitis C virus (HCV) is detectable in saliva by polymerasechain reaction (PCR), suggesting a possible source of HCVinfection.1,2 During treatment or after remission of hepatitis,patients sometimes receive dental treatment. We have examined the