- Email: [email protected]
CORONARY CARE: THE NEXT STEP
1362 definite improvement in renal function, two showed continuing deterioration but at a slower rate, and one patient had a fatal second myocardial infarction after 8 months of treatment and was not included in the follow-up results. Urine protein excretion also fell and serum albumin concentrations increased. These beneficial effects were maintained for 14 (SD 2) months after the end of
cyclophosphamide therapy. Both studies highlight the need for a controlled trial of immunosuppressive treatment in a subgroup of patients with membranous nephropathy and deteriorating renal function. Reported side-effects from chlorambucil appeared to be greater than those with cyclophosphamide. Chlorambucil is less familiar to nephrologists, whereas cyclophosphamide has become the drug of choice in patients with vasculitis and is also used in some patients with renal transplants. The role of either concurrent or alternate prednisolone in membranous nephropathy appears questionable. The consensus in Europe is that prednisolone is rarely useful in this disease and is not without side-effects. Why not consider a trial of daily cyclophosphamide for 12-24 months, since it is a drug with we are more familiar, it may be a little less toxic than chlorambucil, and it has equally tantalising preliminary support?
which
Medical Renal Unit,
Royal Infirmary, Edinburgh EH3 9YW
C. P. SWAINSON A
controlled
trial
of Jindal KK, Bare RA, Goldstein MB. cyclophosphamide in patients with membranous glomerulonephritis. Kidney Int 1987; 32: 579-84.
1. West ML,
seek medical attention-and provided community emergency cardiac care, then the community hospital could provide the link-up between early ischaemic disease and optimum cardiac care. Yes, CCUs have been a success, but they can be even more successful if we take advantage of thrombolytic care by bringing in chest pain awareness programmes on a scale and scope very similar to the US National Awareness Program for cholesterol,
hypertension, and smoking. Dudley White Coronary Care System, St Agnes Hospital, Baltimore, Maryland 21229, USA Paul
RAYMOND D. BAHR
ANTENATAL SCREENING FOR DOWN SYNDROME
SIR,-Dr Ruta and Dr Leece (Sept 24, p 752) agree with our conclusions that a screening policy based on the biochemical testing of the mother’s serum detects more pregnancies associated with Down syndrome and requires fewer amniocenteses than a policy based on maternal age alone.’ They go on to estimate the detection rate and false-positive rate associated with four screening policies in Eastbourne, taking into account local data on maternal age at birth and our results on screening using maternal serum a-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic
gonadotropin (hCG). SCREENING FOR DOWN SYNDROME BY FOUR SCREENING POLICIES: EASTBOURNE DISTRICT
1983-87, AND ENGLAND
AND WALES
1981-85
CORONARY CARE: THE NEXT STEP
SjR,—Not until the last sentence of your Oct 8 editorial does the reader get the feeling that coronary care units (CCUs) have been successful, and then only by the gentle statement "it has been a good idea". CCUs have been a great idea. They have been catalytic in our understanding many aspects of heart attacks. Acute myocardial infarction is the number one killer in the United States but it may be on the downturn, with further improvements in coronary care. CCUs grew out of cardiopulmonary resuscitation (CPR). It did not take long for every hospital in the United States to have a CCU, once it was found that patients’ lives could be saved by either shocking the chest or administering lignocaine. Interestingly, lignocaine was used as "holy water" in CCUs a decade before the US Food and Drug Administration gave approval for this use. CCUs have been clinical research benches for the past 25 years. When it became impossible to salvage any more lives or cardiac muscle by fine tuning of three generations of Swan Ganz catheter information (filling pressure, cardiac output, and SV02), interest moved away from the infarcted area upstream to the acute coronary occlusion itself Progress here was delayed for a while because of cardiac pathologists who thought that thrombosis was a postmortem event. However, the truth emerged, and we are now in an era of thrombolytic care, with drugs and angioplasty. Dr Eugene Braunwald was recently quoted as saying "We are at the stage now with thrombolytic therapy that we were in 1962 when CPR initiated the catalytic step that catapulted us over the last twenty-five years". If so, what is needed for another quantum jump? Do we need more in-depth cardiac research? Or do we have the ingredients now to form a well-engineered plan to wipe out this disease? The identification of risk factors (hypertension, smoking, cholesterol) coupled with national awareness programmes has reduced the incidence of coronary disease itself. Perhaps what we need now is the identification of a risk factor for the acute ischaemic event that would prevent sudden death and myocardial damage and bring the patient to the hospital at the unstable angina stage, where cardioprotection with nitrates, beta blockers, calcium blockers, aspirin, or heparin would permit identification of the obstructive coronary lesion by cardiac catheterisation and its correction by
angioplasty and/or bypass surgery. The United States has 6700 hospitals. If they all extended their CCUs into the community and emphasised the prodrome of a heart attack-namely, the mild chest discomfort in a stuttering pattern centrally located in the chest but not severe enough for the victim to
positive if. (policy A) maternal age 35 or more; (policy B-D) risk of a Down syndrome term pregnancy greater than or equal to cut-off risk. Detection rate=proportion of affected pregnancies with a positive result. False-positive rate proportion of unaffected pregnancies with a positive result. *Estimates by Ruta and Leece are detection rates = 46,50,85, and 77% for policies A, B, C, and D, respectively; false-positive rates 12, 10, 11, and 7-7% for policies A, B, C, and D, respectively. Result
=
Their estimates are incorrect, and the correct ones are shown in the table, together with those that apply to England and Wales as a whole. Policy D, with all four screening variables (age, AFP, uE3, and hCG) is associated with a slightly higher detection rate and false-positive rate in Eastbourne than in England and Wales as a whole. To achieve a 5% false-positive rate in Eastbourne a somewhat higher risk cut-off level (1:220) should be used, and this would also yield a detection rate of 61 %. Department of Environmental and Preventive Medicine, Medical College of St Bartholomew’s Hospital, London EC1M 6BQ
NICHOLAS WALD HOWARD CUCKLE PATRICK ROYSTON
NJ, Cuckle HS, Densem JW, et al. Maternal serum screening for Down’s syndrome in early pregnancy. Br Med J 1988; 297: 883-87
1. Wald
PARENTERAL CITRIC ACID FOR ALUMINIUM INTOXICATION
SIR,-Dr Hewitt and colleagues (Oct 8, p 849) report increases in aluminium in some patients with chronic renal failure who were taking both aluminium-containing phosphate-binder and oral citrate. These findings are supported in animal studiesl-3 and in man.’ However, we have shown that intraperitoneal administration serum
of citric acid enhances aluminium excretion in mice.5-7 Citric acid was the most effective chelator and may be a therapeutic alternative to the use of desferrioxamine in aluminium toxicity; several complications were associated with desferrioxamine use.7 Citrate
cyclophosphamide therapy. Both studies highlight the need for a controlled trial of immunosuppressive treatment in a subgroup of patients with membranous nephropathy and deteriorating renal function. Reported side-effects from chlorambucil appeared to be greater than those with cyclophosphamide. Chlorambucil is less familiar to nephrologists, whereas cyclophosphamide has become the drug of choice in patients with vasculitis and is also used in some patients with renal transplants. The role of either concurrent or alternate prednisolone in membranous nephropathy appears questionable. The consensus in Europe is that prednisolone is rarely useful in this disease and is not without side-effects. Why not consider a trial of daily cyclophosphamide for 12-24 months, since it is a drug with we are more familiar, it may be a little less toxic than chlorambucil, and it has equally tantalising preliminary support?
which
Medical Renal Unit,
Royal Infirmary, Edinburgh EH3 9YW
C. P. SWAINSON A
controlled
trial
of Jindal KK, Bare RA, Goldstein MB. cyclophosphamide in patients with membranous glomerulonephritis. Kidney Int 1987; 32: 579-84.
1. West ML,
seek medical attention-and provided community emergency cardiac care, then the community hospital could provide the link-up between early ischaemic disease and optimum cardiac care. Yes, CCUs have been a success, but they can be even more successful if we take advantage of thrombolytic care by bringing in chest pain awareness programmes on a scale and scope very similar to the US National Awareness Program for cholesterol,
hypertension, and smoking. Dudley White Coronary Care System, St Agnes Hospital, Baltimore, Maryland 21229, USA Paul
RAYMOND D. BAHR
ANTENATAL SCREENING FOR DOWN SYNDROME
SIR,-Dr Ruta and Dr Leece (Sept 24, p 752) agree with our conclusions that a screening policy based on the biochemical testing of the mother’s serum detects more pregnancies associated with Down syndrome and requires fewer amniocenteses than a policy based on maternal age alone.’ They go on to estimate the detection rate and false-positive rate associated with four screening policies in Eastbourne, taking into account local data on maternal age at birth and our results on screening using maternal serum a-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic
gonadotropin (hCG). SCREENING FOR DOWN SYNDROME BY FOUR SCREENING POLICIES: EASTBOURNE DISTRICT
1983-87, AND ENGLAND
AND WALES
1981-85
CORONARY CARE: THE NEXT STEP
SjR,—Not until the last sentence of your Oct 8 editorial does the reader get the feeling that coronary care units (CCUs) have been successful, and then only by the gentle statement "it has been a good idea". CCUs have been a great idea. They have been catalytic in our understanding many aspects of heart attacks. Acute myocardial infarction is the number one killer in the United States but it may be on the downturn, with further improvements in coronary care. CCUs grew out of cardiopulmonary resuscitation (CPR). It did not take long for every hospital in the United States to have a CCU, once it was found that patients’ lives could be saved by either shocking the chest or administering lignocaine. Interestingly, lignocaine was used as "holy water" in CCUs a decade before the US Food and Drug Administration gave approval for this use. CCUs have been clinical research benches for the past 25 years. When it became impossible to salvage any more lives or cardiac muscle by fine tuning of three generations of Swan Ganz catheter information (filling pressure, cardiac output, and SV02), interest moved away from the infarcted area upstream to the acute coronary occlusion itself Progress here was delayed for a while because of cardiac pathologists who thought that thrombosis was a postmortem event. However, the truth emerged, and we are now in an era of thrombolytic care, with drugs and angioplasty. Dr Eugene Braunwald was recently quoted as saying "We are at the stage now with thrombolytic therapy that we were in 1962 when CPR initiated the catalytic step that catapulted us over the last twenty-five years". If so, what is needed for another quantum jump? Do we need more in-depth cardiac research? Or do we have the ingredients now to form a well-engineered plan to wipe out this disease? The identification of risk factors (hypertension, smoking, cholesterol) coupled with national awareness programmes has reduced the incidence of coronary disease itself. Perhaps what we need now is the identification of a risk factor for the acute ischaemic event that would prevent sudden death and myocardial damage and bring the patient to the hospital at the unstable angina stage, where cardioprotection with nitrates, beta blockers, calcium blockers, aspirin, or heparin would permit identification of the obstructive coronary lesion by cardiac catheterisation and its correction by
angioplasty and/or bypass surgery. The United States has 6700 hospitals. If they all extended their CCUs into the community and emphasised the prodrome of a heart attack-namely, the mild chest discomfort in a stuttering pattern centrally located in the chest but not severe enough for the victim to
positive if. (policy A) maternal age 35 or more; (policy B-D) risk of a Down syndrome term pregnancy greater than or equal to cut-off risk. Detection rate=proportion of affected pregnancies with a positive result. False-positive rate proportion of unaffected pregnancies with a positive result. *Estimates by Ruta and Leece are detection rates = 46,50,85, and 77% for policies A, B, C, and D, respectively; false-positive rates 12, 10, 11, and 7-7% for policies A, B, C, and D, respectively. Result
=
Their estimates are incorrect, and the correct ones are shown in the table, together with those that apply to England and Wales as a whole. Policy D, with all four screening variables (age, AFP, uE3, and hCG) is associated with a slightly higher detection rate and false-positive rate in Eastbourne than in England and Wales as a whole. To achieve a 5% false-positive rate in Eastbourne a somewhat higher risk cut-off level (1:220) should be used, and this would also yield a detection rate of 61 %. Department of Environmental and Preventive Medicine, Medical College of St Bartholomew’s Hospital, London EC1M 6BQ
NICHOLAS WALD HOWARD CUCKLE PATRICK ROYSTON
NJ, Cuckle HS, Densem JW, et al. Maternal serum screening for Down’s syndrome in early pregnancy. Br Med J 1988; 297: 883-87
1. Wald
PARENTERAL CITRIC ACID FOR ALUMINIUM INTOXICATION
SIR,-Dr Hewitt and colleagues (Oct 8, p 849) report increases in aluminium in some patients with chronic renal failure who were taking both aluminium-containing phosphate-binder and oral citrate. These findings are supported in animal studiesl-3 and in man.’ However, we have shown that intraperitoneal administration serum
of citric acid enhances aluminium excretion in mice.5-7 Citric acid was the most effective chelator and may be a therapeutic alternative to the use of desferrioxamine in aluminium toxicity; several complications were associated with desferrioxamine use.7 Citrate