476 intestinal cells contain a cross-reactive material detectable with their antibodies but not with ours. We can, however, confirm the presence of V.I.P.-containing cells in certain diarrhœogenic
tumours.’ I note that Dr Bloom and his colleagues now seem to have abandoned their view89 that all classical cases of the watery diarrhoea (w.D.H.A.) syndrome are caused by v.i.p. hypersecretion, and that they, in support of findings described in my letter, also have encountered W.D.H.A. patients who have normal v.i.p. levels and greatly raised levels of human pancreatic polypeptide (H.P.P.). Thus their data corroborate my suggestion that some cases of this syndrome are caused by H.P.P. and some by v.t.P. hypersecretion. In support for the role of V.LP. in causing the W.D.H.A. syndrome Dr Bloom and his colleagues mention unpublished observations concerning the diarrhreogenic effect of v.i.p. infusions in pigs. It should be noted that the pancreatic polypeptide is also a potent diarrhceogenic agent and that it was patented as a veterinary laxative. 10 With the recognition, by Dr Bloom and co-workers, that not all cases of the classical W.D.H.A. syndrome may be explained by v.t.P. hypersecretion the suggestion that other factors may cause or contribute to the symptoms now seems self-evident. Institute of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark
HOW DOES DANAZOL WORK?
SIR Lind and Cook’ question the alleged anti-gonadotrophic properties of danazol though readily agreeing to the drug’s efficacy in endometriosis. They are correct in suggestmg
"that more needs to be learned about its mode of action, which may be multifocal" but they are not entirely correct in dis counting its antigonadrophic action. Though danazol does not appreciably alter serum follicle-stimulating hormone (F.S.H, and luteinising hormone (L.H.) values in normal ovulaton women, it does abolish the major L.H. and minor F.s.H, mid-cycle ovulatory surge. Serum F.s.H. and L.H. values remain within normal range except for occasional erratic peaks of L.H. unrelated to ovulation (see figure).2 Danazol indeed has
L. -I. LARSSON
ANTIBIOTIC PROPHYLAXIS IN GASTROINTESTINAL SURGERY
SIR,—The aetiology of postoperative wound infection is multifactorial with, perhaps, the nature of the operative procedure and the surgeon performing it the most important factors. Mr Griffiths and his colleagues (Aug. 14, p. 325) show, in table n, broad groups of operations each containing relatively few cases. They state that, as indicated in the table, both control and trial groups are similar. Many studies, however (including that of Gilmore and Martin"), have shown that the wound-infection rate after appendicectomy depends on whether the
appendix is normal, minimally inflamed, or gangrenous. Similarly, were the cholecystectomies done as emergency or elective procedures, were the vagotomy and pyloroplasties done as emergencies after a perforation or haematemesis or were they done electively? Surely with such small numbers it would have been better to concentrate on one or two kinds of operation, preferably performed by one surgeon. This would have eli’minated many of the variables. There is little doubt that antibiotics given systematically preoperatively or during operating do reduce wound-infection rates after potentially contaminated or contaminated operations. I agree with The Lancet’s editorial argument12 that it is logical to use an antibiotic agent such as povidone iodine spray in the operative wound at the end of operation. This agent has been shown to reduce the wound-infection rate.’2 The editorial also suggests that systemic chemotherapy with the local application of povidone iodine might do even better than one agent alone. Perhaps the best combination might be a single dose of gentamicin or tobramycin with lincomycin (as suggested by Mr Griffiths and his colleagues) with povidone iodine sprayed into the wound at the end of operation. Inverness Inverness
Hospitals,
J.
R. C. LOGIE
Larsson, L. -I., Schwartz, T., Lundquist, G., Chance, R. E., Sundler, F., Rehfeld, J. F., Grimelius, L., Fahrenkrug, J., Schaffalitzky de Muckadell, O., Moon, N. Am. J. Path. (in the press). 8. Bloom, S. R., Polak, J M. in Gastrointestinal Hormones (edited by J. C. Thompson); p. 635. Austin, Texas, 1975. 9. Bloom, S. R., Polak, J. M. Clin. Endocr. 1976, 5, suppl. p. 223. 10. Chance, R. E., Jones, W. E. United States Patent Office, Oct. 15, 1974. 11. Gilmore, O. J. A., Martin, T. D. M. Br. J. Surg. 1974, 61, 281. 12. Lancet, 1976, i, 73. 7.
Doy
of
Serum F.S.H. and L.H. before and
Cycle
during a course of danazol.
The patient was a 26-year-old woman with severe dysmenorrhrea. Note the abolition of the F.s.H. and L.H. surge at mid-cycle and moderate L.H. peak toward the end of danazol therapy. Endometrial biopsy (V=E-) was atrophic, and the basal body temperature chan (not shown) was uniphasic. (From Greenblatt et al.2)
antigonadotrophic properties depending on the variables studied and the precise definition of the term. For instance, this agent lowers the raised serum F.s.H. and L.H. levels of postmenopausal women; the suppression is only moderate (25-50%) but it is definite. Danazol suppresses the post-castration rise of F.S.H. and L.H. in immature rats; the levels remain at the precastration level. A variety of animal experiments show decided antigonadotrophic activity, such as th; prevention of gonadal hypertrophy after unilateral gonada! extirpation.45s
For some time I have claimed an anti-endometrial proclivity for this drug because striking regressive changes of the endr metrium occur despite persistence of more or less normal gocadotrophic levels.6 I prefer to speak of danazol as an "impeded androgen" with relative antigonadotrophic activity. The capacity of this agent to thwart the mid-cycle surge of L.H, adds; new dimension to contraceptive modalities. The modus 1. Lind, T., Cook, D. Lancet, 1976, i, 1401. 2. Greenblatt, R. B , Borenstein, R., Hernandez-Ayup, S Am JObstet. Gynec. 1974, 118, 783. 3. Eldridge, J. C., Dmowski, W. P., Mahesh, V. B. Biol. Reprod. 1974, 10, 438. 4. Dmowski, W P., Scholer, H. F. L., Mahesh, V B., Greenblatt, R B Fertil. Steril. 1971, 22, 9. 5. Potts, G. O., Beyler, A. L., Schane, H. P. ibid. 1974, 25, 367 6. Greenblatt, R. B., Dmowski, W. P., Mahesh, V. B., Scholler, H F L. 1971, 22, 102.
ibid.
tumours.’ I note that Dr Bloom and his colleagues now seem to have abandoned their view89 that all classical cases of the watery diarrhoea (w.D.H.A.) syndrome are caused by v.i.p. hypersecretion, and that they, in support of findings described in my letter, also have encountered W.D.H.A. patients who have normal v.i.p. levels and greatly raised levels of human pancreatic polypeptide (H.P.P.). Thus their data corroborate my suggestion that some cases of this syndrome are caused by H.P.P. and some by v.t.P. hypersecretion. In support for the role of V.LP. in causing the W.D.H.A. syndrome Dr Bloom and his colleagues mention unpublished observations concerning the diarrhreogenic effect of v.i.p. infusions in pigs. It should be noted that the pancreatic polypeptide is also a potent diarrhceogenic agent and that it was patented as a veterinary laxative. 10 With the recognition, by Dr Bloom and co-workers, that not all cases of the classical W.D.H.A. syndrome may be explained by v.t.P. hypersecretion the suggestion that other factors may cause or contribute to the symptoms now seems self-evident. Institute of Medical Biochemistry, University of Aarhus, DK-8000 Aarhus C, Denmark
HOW DOES DANAZOL WORK?
SIR Lind and Cook’ question the alleged anti-gonadotrophic properties of danazol though readily agreeing to the drug’s efficacy in endometriosis. They are correct in suggestmg
"that more needs to be learned about its mode of action, which may be multifocal" but they are not entirely correct in dis counting its antigonadrophic action. Though danazol does not appreciably alter serum follicle-stimulating hormone (F.S.H, and luteinising hormone (L.H.) values in normal ovulaton women, it does abolish the major L.H. and minor F.s.H, mid-cycle ovulatory surge. Serum F.s.H. and L.H. values remain within normal range except for occasional erratic peaks of L.H. unrelated to ovulation (see figure).2 Danazol indeed has
L. -I. LARSSON
ANTIBIOTIC PROPHYLAXIS IN GASTROINTESTINAL SURGERY
SIR,—The aetiology of postoperative wound infection is multifactorial with, perhaps, the nature of the operative procedure and the surgeon performing it the most important factors. Mr Griffiths and his colleagues (Aug. 14, p. 325) show, in table n, broad groups of operations each containing relatively few cases. They state that, as indicated in the table, both control and trial groups are similar. Many studies, however (including that of Gilmore and Martin"), have shown that the wound-infection rate after appendicectomy depends on whether the
appendix is normal, minimally inflamed, or gangrenous. Similarly, were the cholecystectomies done as emergency or elective procedures, were the vagotomy and pyloroplasties done as emergencies after a perforation or haematemesis or were they done electively? Surely with such small numbers it would have been better to concentrate on one or two kinds of operation, preferably performed by one surgeon. This would have eli’minated many of the variables. There is little doubt that antibiotics given systematically preoperatively or during operating do reduce wound-infection rates after potentially contaminated or contaminated operations. I agree with The Lancet’s editorial argument12 that it is logical to use an antibiotic agent such as povidone iodine spray in the operative wound at the end of operation. This agent has been shown to reduce the wound-infection rate.’2 The editorial also suggests that systemic chemotherapy with the local application of povidone iodine might do even better than one agent alone. Perhaps the best combination might be a single dose of gentamicin or tobramycin with lincomycin (as suggested by Mr Griffiths and his colleagues) with povidone iodine sprayed into the wound at the end of operation. Inverness Inverness
Hospitals,
J.
R. C. LOGIE
Larsson, L. -I., Schwartz, T., Lundquist, G., Chance, R. E., Sundler, F., Rehfeld, J. F., Grimelius, L., Fahrenkrug, J., Schaffalitzky de Muckadell, O., Moon, N. Am. J. Path. (in the press). 8. Bloom, S. R., Polak, J M. in Gastrointestinal Hormones (edited by J. C. Thompson); p. 635. Austin, Texas, 1975. 9. Bloom, S. R., Polak, J. M. Clin. Endocr. 1976, 5, suppl. p. 223. 10. Chance, R. E., Jones, W. E. United States Patent Office, Oct. 15, 1974. 11. Gilmore, O. J. A., Martin, T. D. M. Br. J. Surg. 1974, 61, 281. 12. Lancet, 1976, i, 73. 7.
Doy
of
Serum F.S.H. and L.H. before and
Cycle
during a course of danazol.
The patient was a 26-year-old woman with severe dysmenorrhrea. Note the abolition of the F.s.H. and L.H. surge at mid-cycle and moderate L.H. peak toward the end of danazol therapy. Endometrial biopsy (V=E-) was atrophic, and the basal body temperature chan (not shown) was uniphasic. (From Greenblatt et al.2)
antigonadotrophic properties depending on the variables studied and the precise definition of the term. For instance, this agent lowers the raised serum F.s.H. and L.H. levels of postmenopausal women; the suppression is only moderate (25-50%) but it is definite. Danazol suppresses the post-castration rise of F.S.H. and L.H. in immature rats; the levels remain at the precastration level. A variety of animal experiments show decided antigonadotrophic activity, such as th; prevention of gonadal hypertrophy after unilateral gonada! extirpation.45s
For some time I have claimed an anti-endometrial proclivity for this drug because striking regressive changes of the endr metrium occur despite persistence of more or less normal gocadotrophic levels.6 I prefer to speak of danazol as an "impeded androgen" with relative antigonadotrophic activity. The capacity of this agent to thwart the mid-cycle surge of L.H, adds; new dimension to contraceptive modalities. The modus 1. Lind, T., Cook, D. Lancet, 1976, i, 1401. 2. Greenblatt, R. B , Borenstein, R., Hernandez-Ayup, S Am JObstet. Gynec. 1974, 118, 783. 3. Eldridge, J. C., Dmowski, W. P., Mahesh, V. B. Biol. Reprod. 1974, 10, 438. 4. Dmowski, W P., Scholer, H. F. L., Mahesh, V B., Greenblatt, R B Fertil. Steril. 1971, 22, 9. 5. Potts, G. O., Beyler, A. L., Schane, H. P. ibid. 1974, 25, 367 6. Greenblatt, R. B., Dmowski, W. P., Mahesh, V. B., Scholler, H F L. 1971, 22, 102.
ibid.
