445
(early-onset disease, which in its familial form is linked to CMM866). In sporadic, unselected ovarian cancer we found allele loss at cases
CMM86 in 65% of informative tumours. A gene near this locus is thus of paramount importance in most ovarian cancers. When the gene has been identified, this may have implications for screening. Between 1 and 5% of ovarian cancer occurs in the carriers of a susceptibility gene(S)7 and within this small group it would be worth looking for linkage of 17q probes in those rare ovarian cancer families in which there is no involvement of the breast. CMM86 and pTHH59
were
provided by the HGMP resource centre at
Northwick Park Hospital, and originated in the laboratory of Dr R. White. St
Bartholomew’s, St Thomas’, University College, and Barking Hospitals have been especially helpful in supplying specimens. WILLIAM FOULKES Human Immunogenetics Laboratory DONALD BLACK and Somatic Cell Genetics Laboratory, ELLEN SOLOMON Imperial Cancer Research Fund,
JOHN TROWSDALE
London WC2A 3PX, UK
1. Russell SEH, Hickey GI, Lowry WS, White P, Atkinson RJ. Allele loss from chromosome 17 in ovarian cancer. Oncogene 1990; 5: 1581-83. 2. Eccles DM, Cranston G, Steel CM, Nakamura Y, Leonard RCF. Allele loss on chromosome 17 in human epithelial ovarian cancer. Oncogene 1990; 5: 1599-601. 3. Borrow J, Black DM, Goddard AD, Yagle MK, Frischauf A-M, Solomon E. Construction and regional localization of clones from a Not1 linking library from human chromosome 17q. Genomics 1991; 10: 477-80. 4. Solomon E, Ledbetter DH. Report of the committee on the genetic constitution of chromosome 17. Cytogenet Cell Genet 1990; 55: 198-215. 5. Sato T, Tanigami A, Yamakawa K, et al. Allelotype of breast cancer: cumulative allele losses promote tumor progession in primary breast cancer. Cancer Res 1990; 50: 7184-89. 6. Hall JM, Lee MK, Newman B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990; 250: 1684-89. 7. Ponder BAJ, Easton DF, Peto J. Risk of ovarian cancer associated with a family history: preliminary report of the OPCS study. In: Sharp F, Mason WP, Leake RE, eds. Ovarian cancer, biological and therapeutic challenges. London: Chapman and Hall, 1990: 3-6.
Ovulation and ovarian
cancer
SIR,-Professor Lowry and colleagues (June 22, p 1544) report a molecular basis for the hypothesis that incessant ovulation may be a risk factor in ovarian cancer. I would add my comments. Most ovarian cancers arise on the surface epithelium of the ovary, which is subjected to regular episodes of rupture and repair through ovulation. The table shows three patients (1-3) in whom there is a direct chronological relation between hormonal stimulation of previously unremarkable ovaries and the development of ovarian carcinoma. The fourth patient attended our clinic. This patient received stimulation for several months with clomiphene, concluding with additional follicle stimulating hormone/luteinising hormone (FSH/LH). She had laparoscopically confirmed endometriosis genitalis extema. This was first treated with buserelin for 6 months. Follow-up laparoscopy showed no focus of endometriosis, and the ovaries were unremarkable. Thereafter the patient underwent cyclical stimulation with clomiphene for 1 year, at the end of which she received stimulation with 900 IU FSH and LH for one cycle. Stimulation was then stopped because of the development of ovarian cysts, which were assumed to be endometriotic cysts. Cysts measuring 4 x7 cm were detected by ultrasound, on both sides of the ovaries. The patient was then given FOLLICULAR STIMULATION AND DEVELOPMENT OF OVARIAN CANCER
gonadotropin-releasing hormone analogue ’Decapeptyl Retard’ for 4 months. The cysts persisted, however, and laparotomy was done. A tumour mass affecting both ovaries and the omentum majus (FIGO stage lilb) was detected. Histological tests showed papillary serous adenocarcinoma with metastases in the omentum majus. Even though such individual reports do not prove a direct connection between stimulation and the induction of ovarian neoplasms, it is nevertheless possible that an existent tumour is substantially stimulated by this hormonal therapy. It is worrying that the tumours developed with remarkable rapidity in all four
patients. Department of Obstetrics and Gynaecology, University of Tubingen, 7400 Tübingen, Germany
J. DIETL
1. Atlas M, Merczer J. Massive hyperstimulation and borderline carcinoma of the ovary. A possible association. Acta Obstet Gynecol Scand 1982; 61: 2613. 2. Bamford JM, Steele SJ. Uterine and ovarian carcinoma in a patient receiving gonadotropin therapy: case report. BrJ Obstet Gynaecol 1982; 89: 962-64. 3. Carter ME, Joyce DN. Ovarian carcinoma in a patient hyperstimulated by gonadotrophin therapy for in vitro fertilization: a case report. J In Vitro Fert
Embryo Transf 1987; 4: 126-28.
Cysteinyl-leukotriene receptor antagonist, bronchoconstriction, and airway hyperreactivity SIR,-Dr Taylor and colleagues (March 23, p 690) describe the effect of the
cysteinyl-leukotriene receptor antagonist ICI 204.219 allergen-induced bronchoconstriction and airway hyperreactivity. In our opinion a beneficial effect of this drug on late bronchoconstriction and allergen-induced airway hyperreactivity remains speculative. Allergen-induced late bronchoconstriction usually begins 3-4 h after allergen challenge, peaks at 8-12 h, and on
resolves within 24 h.1,2 It is therefore better to suggest a beneficial effect on the onset of the late response. Allergen-induced increase in bronchial hyperreactivity was measured at 6 h. In all patients, severe bronchoconstriction was present at that time (18-60% reduction in forced expiratory volume from baseline values). The suggested increase in hyperreactivity may (at least partly) be the result of the obstruction.3 It would have been better to measure a possible allergen-induced increase in hyperreactivity between the early and late reaction or after the late reaction, when FEV1 had returned to baseline.4 The effect of ICI 204.219 on PC, histamine may thus be a consequence of the reduction of airway calibre and not of allergen-induced increase in bronchial hyperreactivity. Department of Allergology, University Hospital, 9713 EZ Groningen, Netherlands
R. AALBERS J. G. R. DE MONCHY
O’Byrne JM, Dolovich J, Hargreave FE. Late asthmatic responses. Am Rev Respir Dis 1987; 136: 740-51. 2. Durham SR. The significance of late responses in asthma, Clin Exp Allergy 1991; 21: 1.
3-7. 3. Tattersfield AE. Measurement of bronchial reactivity: a question of interpretation. Thorax 1981; 36: 561-65. 4. Durham SR, Craddock CF, Cookson WO, Benson MK. Increases in airway responsiveness to histamine precede allergen induced late asthmatic response. J Allergy Clin Immunol 1988; 82: 764-70.
Enterococcus faecium with high-level resistance to gentamicin SIR,-We would like to add to the data presented by Dr Woodford and colleagues (June 1, p 1356) and Dr Wade and
*Pat!ent 1 reported in ref 1, patient 2 in ref 2, patient 3 In our clinic HCG = human chorionic gonadotropm
in
ref 3, and patient 4 was seen
colleagues (June 29, p 1616) about high-level gentamicin resistance (HLGR) in Enterococcus faecium. Over the past 2 years in our laboratory, we have used high-content (100 flg) gentamicin discs (Mast) to examine clinically significant isolates of enterococci for HLGR.1 Of 1620 isolates of enterococci from different patients, 108 (67%) showed HLGR (disc diffusion test). Gentamicin susceptibility of 66 of the isolates was examined by an agar dilution method; 62 had confirmed HLGR (minimum inhibitory concentrations [MICs] 5=2000 mg/1). 8 of the 62 strains were identified as E faecium.
(early-onset disease, which in its familial form is linked to CMM866). In sporadic, unselected ovarian cancer we found allele loss at cases
CMM86 in 65% of informative tumours. A gene near this locus is thus of paramount importance in most ovarian cancers. When the gene has been identified, this may have implications for screening. Between 1 and 5% of ovarian cancer occurs in the carriers of a susceptibility gene(S)7 and within this small group it would be worth looking for linkage of 17q probes in those rare ovarian cancer families in which there is no involvement of the breast. CMM86 and pTHH59
were
provided by the HGMP resource centre at
Northwick Park Hospital, and originated in the laboratory of Dr R. White. St
Bartholomew’s, St Thomas’, University College, and Barking Hospitals have been especially helpful in supplying specimens. WILLIAM FOULKES Human Immunogenetics Laboratory DONALD BLACK and Somatic Cell Genetics Laboratory, ELLEN SOLOMON Imperial Cancer Research Fund,
JOHN TROWSDALE
London WC2A 3PX, UK
1. Russell SEH, Hickey GI, Lowry WS, White P, Atkinson RJ. Allele loss from chromosome 17 in ovarian cancer. Oncogene 1990; 5: 1581-83. 2. Eccles DM, Cranston G, Steel CM, Nakamura Y, Leonard RCF. Allele loss on chromosome 17 in human epithelial ovarian cancer. Oncogene 1990; 5: 1599-601. 3. Borrow J, Black DM, Goddard AD, Yagle MK, Frischauf A-M, Solomon E. Construction and regional localization of clones from a Not1 linking library from human chromosome 17q. Genomics 1991; 10: 477-80. 4. Solomon E, Ledbetter DH. Report of the committee on the genetic constitution of chromosome 17. Cytogenet Cell Genet 1990; 55: 198-215. 5. Sato T, Tanigami A, Yamakawa K, et al. Allelotype of breast cancer: cumulative allele losses promote tumor progession in primary breast cancer. Cancer Res 1990; 50: 7184-89. 6. Hall JM, Lee MK, Newman B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990; 250: 1684-89. 7. Ponder BAJ, Easton DF, Peto J. Risk of ovarian cancer associated with a family history: preliminary report of the OPCS study. In: Sharp F, Mason WP, Leake RE, eds. Ovarian cancer, biological and therapeutic challenges. London: Chapman and Hall, 1990: 3-6.
Ovulation and ovarian
cancer
SIR,-Professor Lowry and colleagues (June 22, p 1544) report a molecular basis for the hypothesis that incessant ovulation may be a risk factor in ovarian cancer. I would add my comments. Most ovarian cancers arise on the surface epithelium of the ovary, which is subjected to regular episodes of rupture and repair through ovulation. The table shows three patients (1-3) in whom there is a direct chronological relation between hormonal stimulation of previously unremarkable ovaries and the development of ovarian carcinoma. The fourth patient attended our clinic. This patient received stimulation for several months with clomiphene, concluding with additional follicle stimulating hormone/luteinising hormone (FSH/LH). She had laparoscopically confirmed endometriosis genitalis extema. This was first treated with buserelin for 6 months. Follow-up laparoscopy showed no focus of endometriosis, and the ovaries were unremarkable. Thereafter the patient underwent cyclical stimulation with clomiphene for 1 year, at the end of which she received stimulation with 900 IU FSH and LH for one cycle. Stimulation was then stopped because of the development of ovarian cysts, which were assumed to be endometriotic cysts. Cysts measuring 4 x7 cm were detected by ultrasound, on both sides of the ovaries. The patient was then given FOLLICULAR STIMULATION AND DEVELOPMENT OF OVARIAN CANCER
gonadotropin-releasing hormone analogue ’Decapeptyl Retard’ for 4 months. The cysts persisted, however, and laparotomy was done. A tumour mass affecting both ovaries and the omentum majus (FIGO stage lilb) was detected. Histological tests showed papillary serous adenocarcinoma with metastases in the omentum majus. Even though such individual reports do not prove a direct connection between stimulation and the induction of ovarian neoplasms, it is nevertheless possible that an existent tumour is substantially stimulated by this hormonal therapy. It is worrying that the tumours developed with remarkable rapidity in all four
patients. Department of Obstetrics and Gynaecology, University of Tubingen, 7400 Tübingen, Germany
J. DIETL
1. Atlas M, Merczer J. Massive hyperstimulation and borderline carcinoma of the ovary. A possible association. Acta Obstet Gynecol Scand 1982; 61: 2613. 2. Bamford JM, Steele SJ. Uterine and ovarian carcinoma in a patient receiving gonadotropin therapy: case report. BrJ Obstet Gynaecol 1982; 89: 962-64. 3. Carter ME, Joyce DN. Ovarian carcinoma in a patient hyperstimulated by gonadotrophin therapy for in vitro fertilization: a case report. J In Vitro Fert
Embryo Transf 1987; 4: 126-28.
Cysteinyl-leukotriene receptor antagonist, bronchoconstriction, and airway hyperreactivity SIR,-Dr Taylor and colleagues (March 23, p 690) describe the effect of the
cysteinyl-leukotriene receptor antagonist ICI 204.219 allergen-induced bronchoconstriction and airway hyperreactivity. In our opinion a beneficial effect of this drug on late bronchoconstriction and allergen-induced airway hyperreactivity remains speculative. Allergen-induced late bronchoconstriction usually begins 3-4 h after allergen challenge, peaks at 8-12 h, and on
resolves within 24 h.1,2 It is therefore better to suggest a beneficial effect on the onset of the late response. Allergen-induced increase in bronchial hyperreactivity was measured at 6 h. In all patients, severe bronchoconstriction was present at that time (18-60% reduction in forced expiratory volume from baseline values). The suggested increase in hyperreactivity may (at least partly) be the result of the obstruction.3 It would have been better to measure a possible allergen-induced increase in hyperreactivity between the early and late reaction or after the late reaction, when FEV1 had returned to baseline.4 The effect of ICI 204.219 on PC, histamine may thus be a consequence of the reduction of airway calibre and not of allergen-induced increase in bronchial hyperreactivity. Department of Allergology, University Hospital, 9713 EZ Groningen, Netherlands
R. AALBERS J. G. R. DE MONCHY
O’Byrne JM, Dolovich J, Hargreave FE. Late asthmatic responses. Am Rev Respir Dis 1987; 136: 740-51. 2. Durham SR. The significance of late responses in asthma, Clin Exp Allergy 1991; 21: 1.
3-7. 3. Tattersfield AE. Measurement of bronchial reactivity: a question of interpretation. Thorax 1981; 36: 561-65. 4. Durham SR, Craddock CF, Cookson WO, Benson MK. Increases in airway responsiveness to histamine precede allergen induced late asthmatic response. J Allergy Clin Immunol 1988; 82: 764-70.
Enterococcus faecium with high-level resistance to gentamicin SIR,-We would like to add to the data presented by Dr Woodford and colleagues (June 1, p 1356) and Dr Wade and
*Pat!ent 1 reported in ref 1, patient 2 in ref 2, patient 3 In our clinic HCG = human chorionic gonadotropm
in
ref 3, and patient 4 was seen
colleagues (June 29, p 1616) about high-level gentamicin resistance (HLGR) in Enterococcus faecium. Over the past 2 years in our laboratory, we have used high-content (100 flg) gentamicin discs (Mast) to examine clinically significant isolates of enterococci for HLGR.1 Of 1620 isolates of enterococci from different patients, 108 (67%) showed HLGR (disc diffusion test). Gentamicin susceptibility of 66 of the isolates was examined by an agar dilution method; 62 had confirmed HLGR (minimum inhibitory concentrations [MICs] 5=2000 mg/1). 8 of the 62 strains were identified as E faecium.
