view, the international association is best described by considering all the data points over the whole cancer range, and In
this was the result presented in the paper. David Forman, Henrik Moller, Michel on
behalf of the EUROGAST Study
Imperial Cancer Research Fund, Cancer Epidemiology Unit, Radcliffe Oxford 0X2 6HE, UK
Protection by human milk IgA against Helicobacter pylori infection in infancy SIR-Helicobacter pylori is ubiquitous in West Africa,1 and in The Gambia most children are infected by age 5 years.2 Factors that influence susceptibility to infection are poorly understood. We have measured the potential protective effect of specific human milk IgA by studying 12 mothers and their infants from a Gambian village in which most infants are breastfed throughout the first 2 years of life.3 We collected 6 to 14 samples of milk from each mother over 9-16 days, at 3-8 months post partum. H pylori IgA was measured by enzyme-linked immunosorbent assay (ELISA), with a method similar to that described for measuring serum antibodies.4 13C-urea breath tests were used to detect H pylori infection in the 12 infants at ages 3, 6, 9, and 12 months, with a test solution containing 100 mg 13C-urea (50 atom % excess). Breath samples were collected at 0, 15, 30, and 60 min after administration of substrate. Isotopic enrichment in expired breath was expressedas Craig corrected delta relative to the international standard Pee Dee belemnite (PDB) limestone. Children with enrichment of 13COin expired breath of 6 or more delta units relative to PDB above baseline at 15,30, and 60 min after ingestion of substrate were diagnosed as infected with H pylori.6 We analysed 114 breastmilk samples. The mean optical density, standard deviation, and ranges for antiH-pylori IgA ELISA reactivities for each of the 12 women are shown in the table. We found a relation between the concentration of specific breastmilk IgA and the age of acquisition of Hpylori infection. By ranking mothers according to the level of anti-H-pylori IgA they secreted (mothers with similar mean values were separated according to the range of specific IgA reactivities), their children could be divided into two groups according to whether or not H pylori infection was diagnosed by 9 months of age (Kruskal-Wallis test, p=0004). All 5 infected children at this age came from the 5 mothers with the lowest specific breastmilk IgA. By 12 months of age, only 3 children were infection free, including the children of the 2 mothers who produced the highest specific breastmilk IgA (n=O.041
*Specific IgA measured at 7-8
post partum; others measured
months post partum. t"C-Urea breath test not done.
Table: Maternal milk anti-H pylori IgA (ELISA optical and H pylori infection during first 12 months of life
Human milk IgA against H pylori can thus protect infants from early acquisition of infection. In The Gambia, as in many parts of the developing world, enteric infections in infancy and childhood are the principal cause of malnutrition and growth faltering. Early infection with H pylori may compromise the gastric acid barrierand facilitate the passage of enteropathogenic bacteria from contaminated foods8 to the immunologically naive infant gut. If so, specific human milk IgA may have a crucial role in delaying the onset of H pylori infection, and maintaining the integrity of the gastric acid barrier, throughout the vulnerable weaning period. J E Thomas, S Austin, A Dale, P McClean, M Harding, WA Coward, L T Weaver MRC Dunn Nutrition Unit, Cambridge CB4 1XJ, UK; and
Keneba, The Gambia
Holcombe C, Omotara BA, Eldridge J, Jones DM. Helicobacter pylori, the most common bacterial infection in Africa: a random serological study. Am J Gastroenterol 1992; 87: 28-30. 2 Thomas JE, Downes RM, Lunn PG, Northrop-Clewes CA, Weaver LT. Seroepidemiology of Helicobacter pylori infection in early childhood. Gut 1991; 32: A1231 (abstr). 3 Prentice A, Prentice AM, Cole TJ, Paul AA, Whitehead RG. Breastmilk antimicrobial factors of rural Gambian mothers I: influence of stage of lactation and maternal plane of nutrition. Acta Paediatr Scand 1984; 73: 796-802. 4 Thomas JE, Whatmore AM, Barer MR, Eastham EJ, Kehoe MA. Serodiagnosis of Helicobacter pylori infection in childhood. J Clin Microbiol 1990; 28: 2641-46. 5 Craig H. Isotopic standards for carbon and oxygen and correction factors for mass-spectrometric analysis of carbon dioxide. Geochim Cosmochim Acta 1957; 12: 133-49. 6 Klein PD, Graham DY. Detection of Campylobacter pylori by the 13C-urea breast test. In: Rathbone BJ, Heatley RV, eds. Campylobacter pylori and gastroduodenal disease. 1st ed. Oxford: Blackwell, 1989: 83-94. 7 Taylor DN, Blaser MR. The epidemiology of Helicobacter pylori infection. Epidemiol Rev 1991; 13: 42-59. 8 Cook GC. Infective gastroenteritis and its relationship to reduce gastric acidity. Scand J Gastroenterol 1985; 20 (suppl 111): 17-22. 1
Venous ulceration SiR-Falanga and Eaglstein (April 17, p 1006) postulate that leg ulcers may be caused by trapping of TGF-P (transforming growth factor-p) and other growth factors by
Growth macromolecules such as fibrin or
process of venous ulceration continues after such trauma. The
suggestion that growth factors maintain tissue integrity, and that a disturbance will cause tissue necrosis, is speculative and in contradiction with the general notion that growth factors are produced as a result of cellular trauma or activation, to initiate repair. In addition, the gross microvascular abnormalities in venous insufficiency,3 consisting of dilation and elongation of capillaries, occlusion of capillaries by microthrombi, and reduction of the number of functional capillaries, combined with the increased diffusion distance for oxygen caused by tissue oedema, sufficiently explain the cause of venous ulceration.
R/C = rifampicin/co-trimoxazole. Table: Median
(range) clinical scores at start and 6 months
Jan Robert Mekkes, Wiete Westerhof Department of Dermatology, University of Amsterdam 1105, Amsterdam, Netherlands
1 2 3
Peptide growth factors and wound healing. Clin Plastic Surg 1990; 17: 421-32. Clark RAF. Cutaneous tissue repair: basic biologic considerations, I. J Am Acad Dermatol 1985; 13: 701-25. Leu HJ. Morphology of chronic venous insufficiency: light and electron microscopic examinations. Vasa 1991; 20: 330-42.
Ciprofloxacin for rhinoscleroma and ozena SiR-Respiratory scleroma is a difficult entity to diagnose and treat.1 Of the wide range of treatments (antibiotic combinations, cytostatic drugs, radiation, and laser),2-6 probably none is ideal. The causative organism, klebsiella, is resistant to most antibiotics and, being intracellular, is not always exposed to sufficient concentrations of drug. A clinical cure is hard to identify because the end-stage is mucosal fibrosis which, even without active infection, interferes with normal function of the upper respiratory tract. The fibrosed mucosa, especially in crusts, can become secondarily infected with bacteria, which may include klebsiella. Most patients are from a low socioeconomic group and cannot afford the antibiotics to which klebsiella is susceptible. We have compared oral short-course ciprofloxacin, which has good intracellular penetration and low toxicity,6 with our institutes usual regimen. All outpatients aged over 12, in whom klebsiella rhinoscleroma or ozena were confirmed by culture and nasal biopsy, entered the study. One group (13 men, 9 women) received rifampicin 300 mg and co-trimoxazole, both twice a day for 6 months. The other group (18 men, 10 women) received ciprofloxacin 250 mg twice daily for 4 weeks (the lowest dose calculated to give adequate intracellular levels for klebsiella in patients weighing less than 50 kg). All patients washed their nose out with saline twice a day to remove crusts and prevent secondary infection. Monthly evaluation for 6 months was by seven different scales: nasal crusting, nasal obstruction, purulent secretions, olfactory changes, dysphonia, cough, and general malaise (O=no symptoms, 1 = present monthly, 2 present weekly, 3 = present daily, 4 always present, and 5 incapacitating). Before treatment, the groups were similar in their scores, except for nasal obstruction which was higher in the rifampicin/co-trimoxazole group (table). Both groups improved over the 6 months, but much more so in the ciprofloxacin group (table). At 2 months, 3(11%) biopsy specimens in the ciprofloxacin cultured positive for klebsiella, compared with 20 (91 %) specimens from the other group. Residual nasal obstruction was due to fibrotic stenosis of the nose, nasopharynx, or larynx. Surgical treatment must be deferred until multiple biopsies fail to show further evidence of active infection, to prevent postoperative reactivation of the disease. Purulent secretions were the best indicator of active infection, and disappeared almost entirely in the ciprofloxacin group. Dysphonia and cough were used as indicators of =
laryngeal activity. Laryngeal fibrosis may lead to permanent hoarseness and stridor. The extreme sensitivity of the voice to even a small amount of fibrosis at the vocal cord level probably accounted for little difference between the treatments. General malaise improved in both groups, partly due to the nasal lavage. Residual olfactory disorders were due to permanent destruction of the olfactory mucosa or to nasal stenosis. In the rifampicin group the inflammatory reaction continued. The clinical improvement in the rifampicin/co-trimoxazole group was more likely due to the natural course of the disease, combined with nasal lavage, than to antimicrobial activity. The regimen we recommend for rhinoscleroma or respiratory scleroma is ciprofloxacin 250-500 mg twice daily for 4 weeks, with meticulous nasal lavage with saline at least once or twice a day until crusting diminishes. Although ciprofloxacin is expensive, the total cost of treatment was less than half that of any other previous regimen, and less than a quarter of the cost of rifampicin/co-trimoxazole for 6 months (at local prices) which does not take into account the increasing default rate with length of treatment. Johannes Borgstein, Eduardo Sada, Ricardo Cortes Departments of Otolaryngology and Infectious Diseases, National Institute of Respiratory Diseases, 14080 Mexico DF, Mexico
Lenis A, Ruff T, et al. Rhinoscleroma. Southern Med J 1988; 81: 1580-82. Gamea AM. Local rifampicin treatment in rhinoscleroma. J Laryngol Otol 1988; 102: 319-21. Toppozada HH, Gafaar HA. The effect of streptomycin and irradiation on rhinoscleroma. J Laryngol Otol 1986; 100: 809-15. Maher AI, Hussam K. Rhinoscleroma: management by carbon dioxide laser. Laryngoscope 1990; 100: 783-88. Zapata A, Barron M. Tratamiento del escleroma respiratorio con ciclofosfamida y tetraciclinas. Anal Soc Mex Orl 1986; 7: 100-02. Sanders CC, Sanders WE. Overview of preclinical studies with ciprofloxacin. Am J Med 1987; 82 (suppl 4A): 2-11.
Treatment of cyclospora infections with co-trimoxazole SIR-Cyclospora cayetanensis is a coccidian that causes diarrhoea in patients in both developed and developing countries.1 The organism has previously been referred to as cyanobacterium and coccidian-like bodies (CLBs).2 In this infection in children in Peru, we saw (over 5 years) seasonality, with infection between January and July. About 25% of infected children had diarrhoea. Chronic diarrhoea lasting a mean of 43 (SD 24) days was reported during an outbreak of CLB infections among expatriates in Nepal. We have confirmed that the organisms in such expatriates were cyclospora oocysts. Cyclospora infection has also been reported in several AIDS patients.3,4 None of 34 patients responded to antimicrobial therapy during the Nepal outbreak. Oral co-trimoxazole attenuated diarrhoeal symptoms in 1 AIDS patient who had persistent CLB shedding for 7 weeks.4