- Email: [email protected]
WITHDRAWAL OF ANTIHYPERTENSIVE THERAPY
1381
only at the beginning of this, but that is no reason for not trying. It is simply not true that doctors know their patients’ blood-pressures; recorded pressures account for 50% or less of the population in all the general-practice series so far reported. The organisation required both for screened diagnosis and long-term management and follow-up of whole general-practice populations has been described.6 Those who have done this know very well it is an arduous task, like any worth-while innovation in medicine; if Professor Sackett wants progress he should be familiar with this work and refer to it. His approach is unfortunately typical of several departments of social medicine that are supposed to lead thought and action in this field, but have in fact given small encouragement to initiatives in the front line of primary care that are now springing up all over the country. If they were to conclude that the creation of an autonomous army of sphygmomanometrists would be wasteful, ineffective, and possibly harmful, we would agree with them. In primary care we already have our defined populations, and against a good deal of passive and some active resistance, we are developing the new attitudes needed to take full clinical advantage of that fact. As the work of Miall, Kannel, Stamler, Freis, and other pioneers of the epidemiology of hypertension becomes widely known and understood, a new generation of primary doctors is emerging, committed to the anticipatory care of small whole populations. Fathered by giants, are they to be led by snails ? Glyncorrwg Health Centre, near Port Talbot, Glamorgan, Wales SA13 3BL.
case-finding efforts will reap only the disadvantages, and the long-term benefits, of the undertaking. Furthermore, if case-finding has been carried out at the request of the physician and has occurred outside the regular course of visits, the physician will have broken an implicit promise that the patient will benefit. not
Department of Clinical Epidemiology and Social Medicine, St. Thomas’s
Hospital Medical School,
London SE1.
DAVID L. SACKETT.
BREAST CANCER AND HYPERTENSION
SIR,-Since the publication of the three papers on reserpine and breast cancer in your issue of Sept. 21, there has been considerable discussion of factors that could account for the differences observed. One of the suggestions was that a history of hypertension is related to .breast cancer, whether or not antihypertensive drugs are used. To investigate this, we examined data from the American Cancer Society’s prospective epidemiological study. This study was started in 1959 when volunteers enrolled more OBSERVED V. EXPECTED BREAST-CANCER DEATHS IN WOMEN WITH AND WITHOUT HISTORY OF HIGH BLOOD-PRESSURE
(American
Cancer
Society Epidemiologic Study 1959-1965)
JULIAN TUDOR HART.
** * We showed these letters to Professor Sackett, whose reply follows.-ED. L. SiR,—The issue is simply this: for a hypertensive citizen benefit, three conditions must be met: (1) his bloodpressure must be measured; (2) he must be recognised as hypertensive, properly evaluated, treated, and followed; (3) he must take his medicine. Evaluations of mass community-wide screening have repeatedly shown that the great majority of screenees have recently been seen by their physicians (Dr Coope is citing the wrong measure) and that these physicians neither label nor treat a large proportion of those who screen positive. Furthermore, studies of newly diagnosed hypertensives have shown rapid deterioration in their compliance with to
medications. However impressively it
screening
cannot come to
meets the first condition, grips with this failure to
mass
meet
conditions (2) and (3), and it is for this reason that it is not a rational approach at the mass multi-practice level. However, the occasional physician who is committed to the detection and treatment of hypertension, is responsible for an unusually compliant list of patients, and has the time, skills, and energy required to meet conditions (2) and (3) forms the basis for the second conclusion of my essay: the justification for hypertension case-finding within certain individual practices. This crucial distinction between mass screening for hypertension and case-finding within individual, committed practices has been missed by both your correspondents. However, Dr Coope’s letter does provide some details of the case-finding operation in such a committed practice, and clinicians will find his description useful. Clinicians who contemplate action at the individual practice level must bear in mind that, to the extent that their clinical management is deficient in meeting conditions (2) or (3), the hypertensive patient identified through their 6.
Coope, J. J. R. Coll. Gen. Practnrs, 1974, 24, 161.
*
Expected based for all
women
on breast-cancer death-rates by 5-year age-groups in study.
than 1 million men and women and asked them to fill out a detailed 4-page questionnaire. Every year for 6 years, the volunteers reported to us which of the subjects they enrolled had died. Death certificates were obtained from State Health Departments. By the end of the 6th follow-up which started Oct. 1, 1965, the volunteers had traced 98-4% of the persons originally enrolled. Over 594,000 women were enrolled and in 6 years, 2194 of them died of breast cancer. We restricted the analysis to the 1111 breast-cancer deaths for whom the original questionnaire did not report a previous history of breast cancer. The observed deaths shown in the accompanying table are for women with and without a history of high blood-pressure on the 1959 questionnaire, who died of breast cancer in 6 years. The expected deaths are based upon the 5-year age-specific breast-cancer death-rates for all women who died of breast cancer. A history of high blood-pressure does not, in itself, appear to be related to breast cancer. Department of Epidemiology and Statistics, American Cancer Society, Inc., New York City, New York 10017, U.S.A.
LAWRENCE GARFINKEL E. CUYLER HAMMOND.
WITHDRAWAL OF ANTIHYPERTENSIVE THERAPY
SiR,-Clonidine hydrochloride (’Catapres’) duced
as
an
hypertension
and
a
agent in 1971.
was
intro-
Rebound withdrawal syndrome may occur after
antihypertensive
1382
discontinuation of the drug.l,2
fatality associated been reported.
To our knowledge no with cessation of clonidine therapy has
°
A 59-year-old male with 24 years’ history of essential hypertension was admitted because control of blood-pressure was unsatisfactory. Regular drug therapy (clonidine 0-3 mg. per day, bethanidine 60 mg. per day, bendrofluazide, potassium supplement) had been omitted for 16 hours before admission, at which time the blood-pressure was 290/160 mm. Hg. Clonidine was reintroduced, but blood-pressure recordings remained unsatisfactory. Signs of left ventricular failure developed and satisfactory control of blood-pressure was not obtained despite additional therapy with intravenous diazoxide, oral bethanidine, and diuretics. The patient had a cardiac arrest 36 hours after admission. At necropsy there was evidence of left ventricular hypertrophy and mild atheroma of the coronary arteries without stenosis. Histological examination showed a very recent myocardial infarction.
It is
possible to prove that the omission of antihypertensive therapy contributed to the fatal sequence of events in this patient whose blood-pressure was poorly controlled. Nevertheless, the association of clonidine withdrawal, even for 8-24 hours, with abrupt rises in blood-pressure, I,2 not
suggests that this may have been a factor. This case re-emphasises the need to avoid the sudden cessation of clonidine therapy in hypertension. Department of Therapeutics and Clinical Pharmacology, University Medical Buildings, Foresterhill, Aberdeen AB9 2ZD.
J. WEBSTER A. JEFFERS D. B. GALLOWAY J. C. PETRIE.
COLD-SENSITIVE STRAIN OF PSEUDOMONAS ÆRUGINOSA FROM URINARY-TRACT INFECTION SiR,--Cold-sensitve (c.s.) mutants of various organisms have been reported.33 These mutants cannot grow at moderately low temperatures as the parent cells can, but develop readily at higher temperatures. The c.s. cells described so far have been derived experimentally by the use of various mutagens, and none seem to have been isolated from natural habitats. A strain of Pseudomonas aeruginosa whih behaved as a C.s. organism was isolated in this hospital from the urine of a patient with a severe urinary-tract infection. When cold sensitivity was suspected, a single colony was selected from the original plate, purified by replating, and a fresh single colony was propagated on nutrient agar (Oxoid blood-agar base no. 2) at 37 °C and the growth preserved by drying. The strain was designated Z24. Growth tests were carried out on nutrient-agar plates using two concentrations of inocula from overnight broth cultures grown at 37 °C. The more concentrated inoculum was a single drop containing approximately 106 organisms, and the less concentrated inoculum was flooded over the surface of the plates to yield approximately a hundred
characteristics displayed during growth at 37 °C. At this temperature colonies of 5-10 mm. developed within 24 hours. Similar colonies also developed rapidly if plates were transferred from the lower to the higher temperature. Approximately 60 other isolates of Ps. aeruginosa were tested in a similar way to Z24. There was, predictably, considerable variation in the results, but all heavy inocula showed visible growth within 24 hours of incubation at 22 and 37 °C. With the lighter inoculum all isolates yielded visible colonies within 48 hours of incubation at these I temperatures. The isolate P. 6erugiiiosa (Z24) thus seems to qualify as a It has an c.s. organism and is being studied further. unstable resistance to gentamicin and it is yet to be determined what relation, if any, this property has to its sensitivity to lower temperatures.
Department of Microbiology, Royal Perth Hospital, Perth, Western Australia 6000.
D. I. ANNEAR D. MACCULLOCH.
BOWIE AND DICK TEST FOR AUTOCLAVES SiR,-In June we reported discrepancies in the results of Bowie and Dick tests.Some of these were noted when doing routine checks on an autoclave later found to be malfunctioning. Others were found in tests on an autoclave into which an air leak had been introduced intentionally. We now report an episode in which the defect in the autoclave had occurred naturally and in which the fault was clearly demonstrated. At a routine monthly check an autoclave gave an unsatisfactory Bowie and Dick test result although earlier that same day a similar test by the C.S.S.D. staff had been found satisfactory. A third test was performed with a new pack containing test tape from the laboratory stock and also from the c.s.s., stock. Once again the laboratory tape indicated a failure and the c.s.s.. tape a pass. The autoclave had no load simulator nor was it equipped with a leak-rate detector, so that much reliance was placed on the sensitivity of the tape-test results. An engineer’s inspection showed that the fault was in the vacuum part of the cycle and the cause was traced to a crack in the vacuum valve diaphragm (see accompanying figures). Because of the absence of a batch number on these tapes, the matter could not be investigated fully. 1.
Morris, C. A., Everall, P. H. Lancet, 1974, i, 1118.
colonies. With the heavy inoculum of Z24 incubated at 22 °C, no visible growth appeared until about 4 days after plating, when a faint film of obviously retarded colonies of varying size began to develop. At 370C this inoculum produced heavy confluent growth within 24 hours. The less concentrated inoculum of Z24 produced no visible colonies at 22 °C within 6 days. Some colonies then began to appear but developed extremely slowly, attaining diameters of no more than 1 mm. after 10 days. The colonies continued to develop slowly but showed none of the rough, spreading Hunyor, S. N., Hansson, L., Harrison, T. S., Hoobler, S. W. Br. med. J. 1973, ii, 209. 2. Hansson, L., Hunyor, S. N., Julius, S., Hoobler, S. W. Am. Heart J. 1973, 85, 605. 3. Roberds, D. R., DeBusk, A. G. J. Bact. 1973, 115, 1121. 1.
Fig. 1-Main
vacuum valve diaphragm: Sanderson Bell clave. Crack in diaphragm arrowed.
auto-
only at the beginning of this, but that is no reason for not trying. It is simply not true that doctors know their patients’ blood-pressures; recorded pressures account for 50% or less of the population in all the general-practice series so far reported. The organisation required both for screened diagnosis and long-term management and follow-up of whole general-practice populations has been described.6 Those who have done this know very well it is an arduous task, like any worth-while innovation in medicine; if Professor Sackett wants progress he should be familiar with this work and refer to it. His approach is unfortunately typical of several departments of social medicine that are supposed to lead thought and action in this field, but have in fact given small encouragement to initiatives in the front line of primary care that are now springing up all over the country. If they were to conclude that the creation of an autonomous army of sphygmomanometrists would be wasteful, ineffective, and possibly harmful, we would agree with them. In primary care we already have our defined populations, and against a good deal of passive and some active resistance, we are developing the new attitudes needed to take full clinical advantage of that fact. As the work of Miall, Kannel, Stamler, Freis, and other pioneers of the epidemiology of hypertension becomes widely known and understood, a new generation of primary doctors is emerging, committed to the anticipatory care of small whole populations. Fathered by giants, are they to be led by snails ? Glyncorrwg Health Centre, near Port Talbot, Glamorgan, Wales SA13 3BL.
case-finding efforts will reap only the disadvantages, and the long-term benefits, of the undertaking. Furthermore, if case-finding has been carried out at the request of the physician and has occurred outside the regular course of visits, the physician will have broken an implicit promise that the patient will benefit. not
Department of Clinical Epidemiology and Social Medicine, St. Thomas’s
Hospital Medical School,
London SE1.
DAVID L. SACKETT.
BREAST CANCER AND HYPERTENSION
SIR,-Since the publication of the three papers on reserpine and breast cancer in your issue of Sept. 21, there has been considerable discussion of factors that could account for the differences observed. One of the suggestions was that a history of hypertension is related to .breast cancer, whether or not antihypertensive drugs are used. To investigate this, we examined data from the American Cancer Society’s prospective epidemiological study. This study was started in 1959 when volunteers enrolled more OBSERVED V. EXPECTED BREAST-CANCER DEATHS IN WOMEN WITH AND WITHOUT HISTORY OF HIGH BLOOD-PRESSURE
(American
Cancer
Society Epidemiologic Study 1959-1965)
JULIAN TUDOR HART.
** * We showed these letters to Professor Sackett, whose reply follows.-ED. L. SiR,—The issue is simply this: for a hypertensive citizen benefit, three conditions must be met: (1) his bloodpressure must be measured; (2) he must be recognised as hypertensive, properly evaluated, treated, and followed; (3) he must take his medicine. Evaluations of mass community-wide screening have repeatedly shown that the great majority of screenees have recently been seen by their physicians (Dr Coope is citing the wrong measure) and that these physicians neither label nor treat a large proportion of those who screen positive. Furthermore, studies of newly diagnosed hypertensives have shown rapid deterioration in their compliance with to
medications. However impressively it
screening
cannot come to
meets the first condition, grips with this failure to
mass
meet
conditions (2) and (3), and it is for this reason that it is not a rational approach at the mass multi-practice level. However, the occasional physician who is committed to the detection and treatment of hypertension, is responsible for an unusually compliant list of patients, and has the time, skills, and energy required to meet conditions (2) and (3) forms the basis for the second conclusion of my essay: the justification for hypertension case-finding within certain individual practices. This crucial distinction between mass screening for hypertension and case-finding within individual, committed practices has been missed by both your correspondents. However, Dr Coope’s letter does provide some details of the case-finding operation in such a committed practice, and clinicians will find his description useful. Clinicians who contemplate action at the individual practice level must bear in mind that, to the extent that their clinical management is deficient in meeting conditions (2) or (3), the hypertensive patient identified through their 6.
Coope, J. J. R. Coll. Gen. Practnrs, 1974, 24, 161.
*
Expected based for all
women
on breast-cancer death-rates by 5-year age-groups in study.
than 1 million men and women and asked them to fill out a detailed 4-page questionnaire. Every year for 6 years, the volunteers reported to us which of the subjects they enrolled had died. Death certificates were obtained from State Health Departments. By the end of the 6th follow-up which started Oct. 1, 1965, the volunteers had traced 98-4% of the persons originally enrolled. Over 594,000 women were enrolled and in 6 years, 2194 of them died of breast cancer. We restricted the analysis to the 1111 breast-cancer deaths for whom the original questionnaire did not report a previous history of breast cancer. The observed deaths shown in the accompanying table are for women with and without a history of high blood-pressure on the 1959 questionnaire, who died of breast cancer in 6 years. The expected deaths are based upon the 5-year age-specific breast-cancer death-rates for all women who died of breast cancer. A history of high blood-pressure does not, in itself, appear to be related to breast cancer. Department of Epidemiology and Statistics, American Cancer Society, Inc., New York City, New York 10017, U.S.A.
LAWRENCE GARFINKEL E. CUYLER HAMMOND.
WITHDRAWAL OF ANTIHYPERTENSIVE THERAPY
SiR,-Clonidine hydrochloride (’Catapres’) duced
as
an
hypertension
and
a
agent in 1971.
was
intro-
Rebound withdrawal syndrome may occur after
antihypertensive
1382
discontinuation of the drug.l,2
fatality associated been reported.
To our knowledge no with cessation of clonidine therapy has
°
A 59-year-old male with 24 years’ history of essential hypertension was admitted because control of blood-pressure was unsatisfactory. Regular drug therapy (clonidine 0-3 mg. per day, bethanidine 60 mg. per day, bendrofluazide, potassium supplement) had been omitted for 16 hours before admission, at which time the blood-pressure was 290/160 mm. Hg. Clonidine was reintroduced, but blood-pressure recordings remained unsatisfactory. Signs of left ventricular failure developed and satisfactory control of blood-pressure was not obtained despite additional therapy with intravenous diazoxide, oral bethanidine, and diuretics. The patient had a cardiac arrest 36 hours after admission. At necropsy there was evidence of left ventricular hypertrophy and mild atheroma of the coronary arteries without stenosis. Histological examination showed a very recent myocardial infarction.
It is
possible to prove that the omission of antihypertensive therapy contributed to the fatal sequence of events in this patient whose blood-pressure was poorly controlled. Nevertheless, the association of clonidine withdrawal, even for 8-24 hours, with abrupt rises in blood-pressure, I,2 not
suggests that this may have been a factor. This case re-emphasises the need to avoid the sudden cessation of clonidine therapy in hypertension. Department of Therapeutics and Clinical Pharmacology, University Medical Buildings, Foresterhill, Aberdeen AB9 2ZD.
J. WEBSTER A. JEFFERS D. B. GALLOWAY J. C. PETRIE.
COLD-SENSITIVE STRAIN OF PSEUDOMONAS ÆRUGINOSA FROM URINARY-TRACT INFECTION SiR,--Cold-sensitve (c.s.) mutants of various organisms have been reported.33 These mutants cannot grow at moderately low temperatures as the parent cells can, but develop readily at higher temperatures. The c.s. cells described so far have been derived experimentally by the use of various mutagens, and none seem to have been isolated from natural habitats. A strain of Pseudomonas aeruginosa whih behaved as a C.s. organism was isolated in this hospital from the urine of a patient with a severe urinary-tract infection. When cold sensitivity was suspected, a single colony was selected from the original plate, purified by replating, and a fresh single colony was propagated on nutrient agar (Oxoid blood-agar base no. 2) at 37 °C and the growth preserved by drying. The strain was designated Z24. Growth tests were carried out on nutrient-agar plates using two concentrations of inocula from overnight broth cultures grown at 37 °C. The more concentrated inoculum was a single drop containing approximately 106 organisms, and the less concentrated inoculum was flooded over the surface of the plates to yield approximately a hundred
characteristics displayed during growth at 37 °C. At this temperature colonies of 5-10 mm. developed within 24 hours. Similar colonies also developed rapidly if plates were transferred from the lower to the higher temperature. Approximately 60 other isolates of Ps. aeruginosa were tested in a similar way to Z24. There was, predictably, considerable variation in the results, but all heavy inocula showed visible growth within 24 hours of incubation at 22 and 37 °C. With the lighter inoculum all isolates yielded visible colonies within 48 hours of incubation at these I temperatures. The isolate P. 6erugiiiosa (Z24) thus seems to qualify as a It has an c.s. organism and is being studied further. unstable resistance to gentamicin and it is yet to be determined what relation, if any, this property has to its sensitivity to lower temperatures.
Department of Microbiology, Royal Perth Hospital, Perth, Western Australia 6000.
D. I. ANNEAR D. MACCULLOCH.
BOWIE AND DICK TEST FOR AUTOCLAVES SiR,-In June we reported discrepancies in the results of Bowie and Dick tests.Some of these were noted when doing routine checks on an autoclave later found to be malfunctioning. Others were found in tests on an autoclave into which an air leak had been introduced intentionally. We now report an episode in which the defect in the autoclave had occurred naturally and in which the fault was clearly demonstrated. At a routine monthly check an autoclave gave an unsatisfactory Bowie and Dick test result although earlier that same day a similar test by the C.S.S.D. staff had been found satisfactory. A third test was performed with a new pack containing test tape from the laboratory stock and also from the c.s.s., stock. Once again the laboratory tape indicated a failure and the c.s.s.. tape a pass. The autoclave had no load simulator nor was it equipped with a leak-rate detector, so that much reliance was placed on the sensitivity of the tape-test results. An engineer’s inspection showed that the fault was in the vacuum part of the cycle and the cause was traced to a crack in the vacuum valve diaphragm (see accompanying figures). Because of the absence of a batch number on these tapes, the matter could not be investigated fully. 1.
Morris, C. A., Everall, P. H. Lancet, 1974, i, 1118.
colonies. With the heavy inoculum of Z24 incubated at 22 °C, no visible growth appeared until about 4 days after plating, when a faint film of obviously retarded colonies of varying size began to develop. At 370C this inoculum produced heavy confluent growth within 24 hours. The less concentrated inoculum of Z24 produced no visible colonies at 22 °C within 6 days. Some colonies then began to appear but developed extremely slowly, attaining diameters of no more than 1 mm. after 10 days. The colonies continued to develop slowly but showed none of the rough, spreading Hunyor, S. N., Hansson, L., Harrison, T. S., Hoobler, S. W. Br. med. J. 1973, ii, 209. 2. Hansson, L., Hunyor, S. N., Julius, S., Hoobler, S. W. Am. Heart J. 1973, 85, 605. 3. Roberds, D. R., DeBusk, A. G. J. Bact. 1973, 115, 1121. 1.
Fig. 1-Main
vacuum valve diaphragm: Sanderson Bell clave. Crack in diaphragm arrowed.
auto-