759
On day 15 after a single subcutaneous injection of IFN-y (2 x 106 Ujm2), PBZDR expression was similarly restored to a normal value in six out of seven X-CGD patients (figure) whereas it remained normal in both patients with the autosomal form (not shown). These data support the hypothesis that PBZDR is another NADPH-oxidase molecular component target of IFN-y in CGD associated with cytochrome b558 deficiency. The PBZDR accommodates not only widely prescribed anxiolytic benzodiazepine compounds, such as diazepam, but also endogenous anxiogenic peptide ligands, which significantly modulate the production of cytokines by murine macrophages4 and human monocytes.A role for PBZDR as a target for neuroimmune interactions involved in host defence against pathogens is worthy of
hitherto in North America. Norfloxacin and ciprofloxacin are the only quinolone drugs licensed in Canada, and recent treatment guidelines suggest ciprofloxacin or norfloxacin as alternative primary treatment regimens for gonococcal infections.5,6 Since the four norfloxacin-resistant isolates were susceptible to ceftriaxone and spectinomycin, cases of suspected treatment failure involving the quinolone drugs should be treated with ceftriaxone. National Laboratory for Sexually Transmitted Diseases, Laboratory Centre for Disease Control, Ottawa, Ontario K1A 0L2, Canada
B, Talbot H. In vitro activity of lomefloxacine against Neisseria gonorrhoeae and Chlamydia trachomatis International Society for Sexually Transmitted Diseases Research, 8th meeting, Copenhagen, Denmark, 1989;
1. Romanowski
consideration. INSERM Unit 25 and CNRS Unit 122, Hôpital Necker, 75743 Paris, France, and Immunohaematology Unit,
Department of Paediatrics, Hôpital des Enfants Malades, Paris
FLORA ZAVALA FLORENCE VEBER VÉRONIQUE TAUPIN ANH THU NGUYEN BÉATRICE DESCAMPS-LATSCHA
1. Zavala F, Veber F, Descamps-Latscha B. Altered expression of neutrophil peripheral benzodiazepine receptor in X-linked chronic granulomatous disease. Blood 1990; 76: 184-88. 2. Ezekowitz RAB, Dinauer MC, Jaffe HS, Orkin SH, Newburger PE. Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med 1988; 319: 146-51. 3. Sechler JM, Malech HL, White CJ, Gallin JI. Recombinant human interferon-y reconstitutes defective phagocyte defect in patients with chronic granulomatous disease of childhood. Proc Natl Acad Sci USA 1988; 85: 4874-78. 4 Zavala F, Taupin V, Descamps-Latscha B. In vivo treatment with benzodiazepines inhibits murine phagocyte oxidative metabolism and production of interleukin 1, tumor necrosis factor, and interleukin 6. J Pharmacol Exp Ther (in press). 5. Taupin V, Herbelin A, Descamps-Latscha B, Zavala F. Endogenous anxiogenic peptide, ODN-diazepam binding inhibitor, and benzodiazepines enhance the production of interleukin-1 and tumor necrosis factor by human monocytes. Lymphokine Res (in press).
Norfloxacin resistant Neisseria gonorrhoeae in North America SiR,—We report the first isolation in North America of Neisseria gonorrhoeae resistant to the quinolone antibiotic norfloxacin. Isolates were submitted as part of a Canadian national surveillance programme for penicillinase-producing N gonorrhoeae (PPNG), and were tested for susceptibility to several antibiotics. Between January, 1989, and April, 1990, four of the PPNG isolates had norfloxacin minimum inhibitory concentrations (MICs) of 20 mg/l. This is 30 or more times the MICs of 900 other PPNG isolates (0-016-0-032 mg/1) tested in our laboratory during the same period. The resistant isolates also had reduced sensitivity to two other quinolones: lomefloxacin (MIC 1-2 mg/1) and ciprofloxacin (MIC 0.25-0-5 mg/1). Previous studies in Canada have shown that the MIC90 of lomefloxacin was 0.032 mg/1 for penicillin-sensitive N1 gonorrhoeae isolates, and 0,063 mg/1 for penicillin-resistant strains. All four isolates were also resistant to tetracycline and erythromycin, but were susceptible to spectinomycin and ceftriaxone. Auxotype/serovar (A/S) typing showed that the norfloxacin-resistant isolates were unrelated. Three of the isolates carried a 4 5 megadalton (MD) &bgr;-lactamase-producing plasmid (Asia type), one with a 24.5MD transfer plasmid; the other isolate carried a 3-05 MD &bgr;-lactamase-producing plasmid and a 24-5 MD
plasmid. The isolates were all recovered from men who were infected outside Canada. One isolate (LCDC 2942) from Alberta had epidemiological links to the Philippines, and two isolates (LCDC 4201 and 4421) from British Columbia were linked to Thailand. The last isolate (LCDC 3931) was taken from a sailor seeking treatment while his ship was docked in Newfoundland. The drugs used for primary treatment of three patients (isolates LCDC 2942, 4201, and 4421) were: spectinomycin and tetracycline; ampicillin plus probenecid and doxycycline; and ceftriaxone, respectively. The case treated with ampicillin, probenecid, and doxycycline was a treatment failure; ceftriaxone treatment was successful. Other reports have documented quinolone-resistant N gonorrhoeae isolates in the Philippines, UK, and Spain,2-4 but not
K. H. YEUNG J. R. DILLON
abstract 98.
Joyce MP, Ayling BB, Vaughan GH, et al In vitro sensitivity of Neisseria gonorrhoeae to quinolone antibiotics in the Republic of the Philippines. Sixth International Pathogenic Neisseria Conference, Atlanta, 1988; abstract E19. 3. Jephcott AE, Turner A. Ciprofloxacin resistance in gonococci. Lancet 1990; 335: 165. 4. Gransden WR, Warren CA, Phillips I, Hodges M, Barlow D. Decreased susceptibility of Neisseria gonorrhoeae to ciprofloxacin. Lancet 1990; 335: 51. 5. Center for Disease Control. 1989 sexually transmitted diseases treatment guidelines. MMWR 1989; 38: 5-8. 6. World Health Organisation. STD treatment strategies (WHO/VDT/89.447). Geneva: WHO, 1989. 2.
Occult
axillary lymph-node micrometastases in breast
cancer
SIR,-Dr Anderson and Dr Galea and colleagues (Aug 18, p 435) report (June 30, p 1565). Unfortunately, one of
comment on our
Anderson’s conclusions is erroneous because he misreads our data. 83 of 921 purported axillary node-negative breast cancer patients proved on serial sectioning to have nodal involvement; in an additional 46 subjects (not among the 921) node involvement was detected by simple histological re-examination of node material. Anderson’s statement that the study yield after serial reexamination was 37 patients (83 minus 46) is therefore clearly incorrect. Galea and colleagues wish that we had addressed the issue of metastatic tumour size and its prognostic importance. Would that we could have done so accurately. The examination of every entire node would have been needed to assess definitively the size and number of foci. This was not possible with the material available to us. We chose to classify as occult axillary lymph-node involvement any lesion irrespective of size, provided that it infiltrated the node substance. The prognostic significance of our results seems to justify this research decision. If continued follow-up reveals that our prognostic conclusions remain valid, then methods, not necessarily morphological, need to be developed to detect axillary nodal involvement in women with breast cancer. A. M. NEVILLE International (Ludwig) R. BETTELHEIM Breast Cancer Study Group, R. D. GELBER Konsumstrasse 13, 3007 Bern, Switzerland A. GOLDHIRSCH
Finger clubbing and tumour necrosis factor &agr; SIR,-Clubbing of fingers and toes is common in patients with non-inflammatory conditions (eg, severe chronic heart failure, congenital cyanotic heart disease, and cancer), and in patients with chronic inflammatory diseases (eg, cystic fibrosis [CF], bronchiectasis, inflammatory bowel disease [IBD], chronic liver disease, and parasitic infestations such
as
trichuris
colitis).1 The
pathological features of clubbing are increased vascularisation of the nail bed with rounding ("watchglass") deformity, oedema, and fibrous overgrowth at the tips of the fingers. Subsequently, periosteal proliferation and hypertrophic osteoarthropathy can appear at the metacarpals, metatarsals, proximal phalanges, and at the distal ends of long bones. A cause has not yet been found, although there are several ideas.2 For example, the neurogenic
On day 15 after a single subcutaneous injection of IFN-y (2 x 106 Ujm2), PBZDR expression was similarly restored to a normal value in six out of seven X-CGD patients (figure) whereas it remained normal in both patients with the autosomal form (not shown). These data support the hypothesis that PBZDR is another NADPH-oxidase molecular component target of IFN-y in CGD associated with cytochrome b558 deficiency. The PBZDR accommodates not only widely prescribed anxiolytic benzodiazepine compounds, such as diazepam, but also endogenous anxiogenic peptide ligands, which significantly modulate the production of cytokines by murine macrophages4 and human monocytes.A role for PBZDR as a target for neuroimmune interactions involved in host defence against pathogens is worthy of
hitherto in North America. Norfloxacin and ciprofloxacin are the only quinolone drugs licensed in Canada, and recent treatment guidelines suggest ciprofloxacin or norfloxacin as alternative primary treatment regimens for gonococcal infections.5,6 Since the four norfloxacin-resistant isolates were susceptible to ceftriaxone and spectinomycin, cases of suspected treatment failure involving the quinolone drugs should be treated with ceftriaxone. National Laboratory for Sexually Transmitted Diseases, Laboratory Centre for Disease Control, Ottawa, Ontario K1A 0L2, Canada
B, Talbot H. In vitro activity of lomefloxacine against Neisseria gonorrhoeae and Chlamydia trachomatis International Society for Sexually Transmitted Diseases Research, 8th meeting, Copenhagen, Denmark, 1989;
1. Romanowski
consideration. INSERM Unit 25 and CNRS Unit 122, Hôpital Necker, 75743 Paris, France, and Immunohaematology Unit,
Department of Paediatrics, Hôpital des Enfants Malades, Paris
FLORA ZAVALA FLORENCE VEBER VÉRONIQUE TAUPIN ANH THU NGUYEN BÉATRICE DESCAMPS-LATSCHA
1. Zavala F, Veber F, Descamps-Latscha B. Altered expression of neutrophil peripheral benzodiazepine receptor in X-linked chronic granulomatous disease. Blood 1990; 76: 184-88. 2. Ezekowitz RAB, Dinauer MC, Jaffe HS, Orkin SH, Newburger PE. Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med 1988; 319: 146-51. 3. Sechler JM, Malech HL, White CJ, Gallin JI. Recombinant human interferon-y reconstitutes defective phagocyte defect in patients with chronic granulomatous disease of childhood. Proc Natl Acad Sci USA 1988; 85: 4874-78. 4 Zavala F, Taupin V, Descamps-Latscha B. In vivo treatment with benzodiazepines inhibits murine phagocyte oxidative metabolism and production of interleukin 1, tumor necrosis factor, and interleukin 6. J Pharmacol Exp Ther (in press). 5. Taupin V, Herbelin A, Descamps-Latscha B, Zavala F. Endogenous anxiogenic peptide, ODN-diazepam binding inhibitor, and benzodiazepines enhance the production of interleukin-1 and tumor necrosis factor by human monocytes. Lymphokine Res (in press).
Norfloxacin resistant Neisseria gonorrhoeae in North America SiR,—We report the first isolation in North America of Neisseria gonorrhoeae resistant to the quinolone antibiotic norfloxacin. Isolates were submitted as part of a Canadian national surveillance programme for penicillinase-producing N gonorrhoeae (PPNG), and were tested for susceptibility to several antibiotics. Between January, 1989, and April, 1990, four of the PPNG isolates had norfloxacin minimum inhibitory concentrations (MICs) of 20 mg/l. This is 30 or more times the MICs of 900 other PPNG isolates (0-016-0-032 mg/1) tested in our laboratory during the same period. The resistant isolates also had reduced sensitivity to two other quinolones: lomefloxacin (MIC 1-2 mg/1) and ciprofloxacin (MIC 0.25-0-5 mg/1). Previous studies in Canada have shown that the MIC90 of lomefloxacin was 0.032 mg/1 for penicillin-sensitive N1 gonorrhoeae isolates, and 0,063 mg/1 for penicillin-resistant strains. All four isolates were also resistant to tetracycline and erythromycin, but were susceptible to spectinomycin and ceftriaxone. Auxotype/serovar (A/S) typing showed that the norfloxacin-resistant isolates were unrelated. Three of the isolates carried a 4 5 megadalton (MD) &bgr;-lactamase-producing plasmid (Asia type), one with a 24.5MD transfer plasmid; the other isolate carried a 3-05 MD &bgr;-lactamase-producing plasmid and a 24-5 MD
plasmid. The isolates were all recovered from men who were infected outside Canada. One isolate (LCDC 2942) from Alberta had epidemiological links to the Philippines, and two isolates (LCDC 4201 and 4421) from British Columbia were linked to Thailand. The last isolate (LCDC 3931) was taken from a sailor seeking treatment while his ship was docked in Newfoundland. The drugs used for primary treatment of three patients (isolates LCDC 2942, 4201, and 4421) were: spectinomycin and tetracycline; ampicillin plus probenecid and doxycycline; and ceftriaxone, respectively. The case treated with ampicillin, probenecid, and doxycycline was a treatment failure; ceftriaxone treatment was successful. Other reports have documented quinolone-resistant N gonorrhoeae isolates in the Philippines, UK, and Spain,2-4 but not
K. H. YEUNG J. R. DILLON
abstract 98.
Joyce MP, Ayling BB, Vaughan GH, et al In vitro sensitivity of Neisseria gonorrhoeae to quinolone antibiotics in the Republic of the Philippines. Sixth International Pathogenic Neisseria Conference, Atlanta, 1988; abstract E19. 3. Jephcott AE, Turner A. Ciprofloxacin resistance in gonococci. Lancet 1990; 335: 165. 4. Gransden WR, Warren CA, Phillips I, Hodges M, Barlow D. Decreased susceptibility of Neisseria gonorrhoeae to ciprofloxacin. Lancet 1990; 335: 51. 5. Center for Disease Control. 1989 sexually transmitted diseases treatment guidelines. MMWR 1989; 38: 5-8. 6. World Health Organisation. STD treatment strategies (WHO/VDT/89.447). Geneva: WHO, 1989. 2.
Occult
axillary lymph-node micrometastases in breast
cancer
SIR,-Dr Anderson and Dr Galea and colleagues (Aug 18, p 435) report (June 30, p 1565). Unfortunately, one of
comment on our
Anderson’s conclusions is erroneous because he misreads our data. 83 of 921 purported axillary node-negative breast cancer patients proved on serial sectioning to have nodal involvement; in an additional 46 subjects (not among the 921) node involvement was detected by simple histological re-examination of node material. Anderson’s statement that the study yield after serial reexamination was 37 patients (83 minus 46) is therefore clearly incorrect. Galea and colleagues wish that we had addressed the issue of metastatic tumour size and its prognostic importance. Would that we could have done so accurately. The examination of every entire node would have been needed to assess definitively the size and number of foci. This was not possible with the material available to us. We chose to classify as occult axillary lymph-node involvement any lesion irrespective of size, provided that it infiltrated the node substance. The prognostic significance of our results seems to justify this research decision. If continued follow-up reveals that our prognostic conclusions remain valid, then methods, not necessarily morphological, need to be developed to detect axillary nodal involvement in women with breast cancer. A. M. NEVILLE International (Ludwig) R. BETTELHEIM Breast Cancer Study Group, R. D. GELBER Konsumstrasse 13, 3007 Bern, Switzerland A. GOLDHIRSCH
Finger clubbing and tumour necrosis factor &agr; SIR,-Clubbing of fingers and toes is common in patients with non-inflammatory conditions (eg, severe chronic heart failure, congenital cyanotic heart disease, and cancer), and in patients with chronic inflammatory diseases (eg, cystic fibrosis [CF], bronchiectasis, inflammatory bowel disease [IBD], chronic liver disease, and parasitic infestations such
as
trichuris
colitis).1 The
pathological features of clubbing are increased vascularisation of the nail bed with rounding ("watchglass") deformity, oedema, and fibrous overgrowth at the tips of the fingers. Subsequently, periosteal proliferation and hypertrophic osteoarthropathy can appear at the metacarpals, metatarsals, proximal phalanges, and at the distal ends of long bones. A cause has not yet been found, although there are several ideas.2 For example, the neurogenic
