- Email: [email protected]
NON-STICK OINTMENT
1008 free-cortisol sufficient to cause mineralocorticoid excess has not yet been reported, but the appropriate investigation of a woman who has become hypertensive while taking an oral contraceptive has not, so far as I know, been described. If adrenal-corticosteroid excess contributes to the development of hypertension in women who take an oral contraceptive, it might be through the combined effect of an increase in the plasma concentration of cortisol, desoxycorticosterone, and aldosterone. The increase may be greater in some women than others for reasons yet unknown, or possibly individual sensitivity to the action of these hormones varies. Whether or not these women have mineralocorticoid excess can be confirmed by a simple study of the colon. Study of the colon of patients with malignant hypertension will be inconclusive because they often have "
secondary " hyperaldosteronism.4
Medical Unit, St. Mary’s Hospital Medical School, London W.2.
PETER RICHARDS.
is surely time that her method
10.
Robinson, M. ibid. 1958, i, 178.
given
a
trial in other
The work on rabbits mentioned in this letter will be fully described in the near future. DAVID F. HORROBIN.
NON-STICK OINTMENT
SiR,-The formula suggested by Mr. David Southcott (Oct. 25, p. 909) contains a potentially dangerous incompatibility. Chlorhexidine forms inactive complexes with anionic surfactants, including stearic-acid soaps. It is particularly important that preparations intended for application to microbial
raw
surfaces should
not
be left without anti-
protection in this way. Chlorhexidine has, in addition, the disadvantage of conferring no protection against fungal growth and of permitting survival of some pseudomonads and related bacteria. I would therefore suggest firstly that the emulgent should be non-ionic (e.g., cetomacrogol emulsifying wax B.P.C.), and secondly that the preservative system should consist of two components: "
ORAL CONTRACEPTIVES AND MALIGNANT HYPERTENSION was interested to read the paper by Dr. Harris SIR,łI (Aug. 30, p. 466) on this subject. I was, however, surprised that he did not mention progestin as a possible cause. The changes in the renin-angiotensin-aldosterone system which he did mention may well be a consequence of the fact that progesterone is an aldosterone antagonist and a powerful sodium-losing diuretic.7 I have demonstrated that progesterone, given daily for several weeks, is capable of producing sustained hypertension in rabbits.8The mechanism of the hypertension is uncertain, but it might be a consequence of the stimulation of the renin system by the sodium loss brought about by the progesterone. I am just completing an experiment in which I compared the effect of giving progesterone (25 mg. per day) to two groups of rabbits. The first group was given plain water to drink and the second group was given 1% saline. I reasoned that the saline would more than compensate for any progesterone-induced sodium loss, and that in the second group there would therefore be no need for an increase in the activity of the renin-angiotensin-aldosterone system. After a few days the arterial pressure in the group drinking plain water rose by about 20 mm. Hg. In contrast, pressure in the saline-treated group rose slightly, but never more than 5 mm. Hg. On substituting plain water for the saline after a period of ten days, the pressure in the second group rose to levels similar to those in the first. This suggests that much of the hypertensive action of progesterone depends on its promotion of sodium loss. This may be important in pre-eclampsia. Gordon et aI.,9 in a prospective study, have recently demonstrated that renin levels are high in pregnant patients who later develop preeclampsia. It is possible that renin levels are high as a consequence of an unusually high progesterone level in those patients. My observations on the protective action of salt also fit in with the important study carried out by Robinson.10 In about 2000 patients she compared the consequences of high and low salt diets started early in pregnancy. The incidences of both pre-eclampsia and perinatal mortality were much lower in the group receiving a high-salt diet. Perhaps because it is so simple, or perhaps because it is so much against established dogma, Robinson’s method for the prophylaxis of pre-eclampsia has been totally ignored. Now that there may be a rational explanation for her findings, it 7. Landau, R. L., Lugibihl, K. Recent Prog. Horm. Res. 1961, 27, 249. 8. Horrobin, D. F. Lancet, 1968, i, 170. 9. Gordon, R. D., Parsons, S., Symonds, E. M. ibid. 1969, i, 347.
was
centres.
"
(a) a chlorhexidine salt which will remain in the aqueous phase and suppress most bacterial contaminants: (b) chlorocresol (at least 0-2%) which will largely partition into the lipid phase where it will restrain fungal development while the fraction remaining in the aqueous phase inhibits organisms not covered by the chlorhexidine.
preservative system has been thoroughly tested bacteriologically and I have known no instance of microbial survival; I cannot comment, for lack of data, on the claim This
that this type of cream is an effective " non-stick " preparation, though I would have thought that any cream " generously applied " would have had much the same effect. Selly Oak Hospital, A. P. LAUNCHBURY. Birmingham 29.
SCHIZOPHRENIA AND DEPRESSION OF LYMPHOCYTE RESPONSE TO P.H.A. SIR,-In their letter of Aug. 23 (p. 440), Dr. Hughes and Professor Field refer to an as yet unpublished study by Knowles et al.1 on lymphocyte response to phytohzmagglutinin (P.H.A.) in schizophrenic patients, and inform us that an inhibitory factor found in the serum of schizophrenics was traced to a phenothiazine used in the treatment of these patients. They add that no depression of lymphocyte transformation occurred with the plasma of patients not receiving this drug. In our study on the same subject 2 we observed a lesser than normal lymphocyte response to phytohaemagglutinin in a group of schizophrenic patients who had not received any drugs for at least six months (and of whom the majority had not received any drugs in the past three years or more). This discrepancy could, of course, be due to differences in sampling procedures (or other differences in the methodology), since in our study we were dealing with a specially selected group of schizophrenics. Our results demonstrate, nevertheless, that a depressed lymphocyte response in schizophrenic patients cannot be attributed exclusively to the drugs used in their treatment. Veterans Administration
Hospital, HILDEGARD R. MARICQ. Lyons, N.J. Department of Medical Genetics, New York State Psychiatric LISSY F. JARVIK Institute, New York, N.Y. JOHN D. RAINER. 1. Knowles, M., Saunders, M., McCelland, H. A. Acta psychiat. scand. (in the press). 2. Maricq, H. R., Jarvik, L. F., Rainer, J. D. Dis. nerv. Syst. 1968, 29, 659.
secondary " hyperaldosteronism.4
Medical Unit, St. Mary’s Hospital Medical School, London W.2.
PETER RICHARDS.
is surely time that her method
10.
Robinson, M. ibid. 1958, i, 178.
given
a
trial in other
The work on rabbits mentioned in this letter will be fully described in the near future. DAVID F. HORROBIN.
NON-STICK OINTMENT
SiR,-The formula suggested by Mr. David Southcott (Oct. 25, p. 909) contains a potentially dangerous incompatibility. Chlorhexidine forms inactive complexes with anionic surfactants, including stearic-acid soaps. It is particularly important that preparations intended for application to microbial
raw
surfaces should
not
be left without anti-
protection in this way. Chlorhexidine has, in addition, the disadvantage of conferring no protection against fungal growth and of permitting survival of some pseudomonads and related bacteria. I would therefore suggest firstly that the emulgent should be non-ionic (e.g., cetomacrogol emulsifying wax B.P.C.), and secondly that the preservative system should consist of two components: "
ORAL CONTRACEPTIVES AND MALIGNANT HYPERTENSION was interested to read the paper by Dr. Harris SIR,łI (Aug. 30, p. 466) on this subject. I was, however, surprised that he did not mention progestin as a possible cause. The changes in the renin-angiotensin-aldosterone system which he did mention may well be a consequence of the fact that progesterone is an aldosterone antagonist and a powerful sodium-losing diuretic.7 I have demonstrated that progesterone, given daily for several weeks, is capable of producing sustained hypertension in rabbits.8The mechanism of the hypertension is uncertain, but it might be a consequence of the stimulation of the renin system by the sodium loss brought about by the progesterone. I am just completing an experiment in which I compared the effect of giving progesterone (25 mg. per day) to two groups of rabbits. The first group was given plain water to drink and the second group was given 1% saline. I reasoned that the saline would more than compensate for any progesterone-induced sodium loss, and that in the second group there would therefore be no need for an increase in the activity of the renin-angiotensin-aldosterone system. After a few days the arterial pressure in the group drinking plain water rose by about 20 mm. Hg. In contrast, pressure in the saline-treated group rose slightly, but never more than 5 mm. Hg. On substituting plain water for the saline after a period of ten days, the pressure in the second group rose to levels similar to those in the first. This suggests that much of the hypertensive action of progesterone depends on its promotion of sodium loss. This may be important in pre-eclampsia. Gordon et aI.,9 in a prospective study, have recently demonstrated that renin levels are high in pregnant patients who later develop preeclampsia. It is possible that renin levels are high as a consequence of an unusually high progesterone level in those patients. My observations on the protective action of salt also fit in with the important study carried out by Robinson.10 In about 2000 patients she compared the consequences of high and low salt diets started early in pregnancy. The incidences of both pre-eclampsia and perinatal mortality were much lower in the group receiving a high-salt diet. Perhaps because it is so simple, or perhaps because it is so much against established dogma, Robinson’s method for the prophylaxis of pre-eclampsia has been totally ignored. Now that there may be a rational explanation for her findings, it 7. Landau, R. L., Lugibihl, K. Recent Prog. Horm. Res. 1961, 27, 249. 8. Horrobin, D. F. Lancet, 1968, i, 170. 9. Gordon, R. D., Parsons, S., Symonds, E. M. ibid. 1969, i, 347.
was
centres.
"
(a) a chlorhexidine salt which will remain in the aqueous phase and suppress most bacterial contaminants: (b) chlorocresol (at least 0-2%) which will largely partition into the lipid phase where it will restrain fungal development while the fraction remaining in the aqueous phase inhibits organisms not covered by the chlorhexidine.
preservative system has been thoroughly tested bacteriologically and I have known no instance of microbial survival; I cannot comment, for lack of data, on the claim This
that this type of cream is an effective " non-stick " preparation, though I would have thought that any cream " generously applied " would have had much the same effect. Selly Oak Hospital, A. P. LAUNCHBURY. Birmingham 29.
SCHIZOPHRENIA AND DEPRESSION OF LYMPHOCYTE RESPONSE TO P.H.A. SIR,-In their letter of Aug. 23 (p. 440), Dr. Hughes and Professor Field refer to an as yet unpublished study by Knowles et al.1 on lymphocyte response to phytohzmagglutinin (P.H.A.) in schizophrenic patients, and inform us that an inhibitory factor found in the serum of schizophrenics was traced to a phenothiazine used in the treatment of these patients. They add that no depression of lymphocyte transformation occurred with the plasma of patients not receiving this drug. In our study on the same subject 2 we observed a lesser than normal lymphocyte response to phytohaemagglutinin in a group of schizophrenic patients who had not received any drugs for at least six months (and of whom the majority had not received any drugs in the past three years or more). This discrepancy could, of course, be due to differences in sampling procedures (or other differences in the methodology), since in our study we were dealing with a specially selected group of schizophrenics. Our results demonstrate, nevertheless, that a depressed lymphocyte response in schizophrenic patients cannot be attributed exclusively to the drugs used in their treatment. Veterans Administration
Hospital, HILDEGARD R. MARICQ. Lyons, N.J. Department of Medical Genetics, New York State Psychiatric LISSY F. JARVIK Institute, New York, N.Y. JOHN D. RAINER. 1. Knowles, M., Saunders, M., McCelland, H. A. Acta psychiat. scand. (in the press). 2. Maricq, H. R., Jarvik, L. F., Rainer, J. D. Dis. nerv. Syst. 1968, 29, 659.