29 OCTOBER 1977
BRITISH MEDICAL JOURNAL
experiments not only to record, the amount of "carbohydrate" but to specify the sort of carbohydrate they have used ? Sucrose produces a very wide range of abnormalities that are not produced by starch.; For example, in the studies referred to in this letter our control animals, which showed no renal abnormalities, were fed exactly similar diets with exactly the same proportion of carbohydrate as were the experimental animals; the difference was only that for the former the dietary carbohydrate was starch and for the latter it was sucrose. K R BRUCKDORFER Royal Free Hospital Medical School, London WCl
1151
These results emphasise the need for caution in prescribing tricyclic antidepressants to elderly patients and once again illustrate the unsuitability of drug dosage as a parameter with which to correlate therapeutic response. Three of the five patients did not in fact suffer side effects of unusual type or severity despite the high levels, but one (B) became ataxic and another (D) suffered a toxic confusional state. Both patients recovered on a reduced dose. A C CARR R P HOBSON Maudsley Hospital, London SE5 Ziegler, V, et al, British Jrournal of Psychiatry, 1977,
131, 168. S S KANG ROBERT G PRICE JOHN YUDKIN Diagnosis of hypertrophic pulmonary
Queen Elizabeth College, London W8
osteoarthropathy
Cohen, A M, and Rosenmann, E, Diabetologia, 1971, 7, 25. Kang, S S, et al, Biochemical Society Transactions, 1977, 5, 235. Kang, S S, et al, Proceedings of the Nutrition Society, 1977, 36, 27A. 4Dance, N, et al, Clinica Chimica Acta, 1970, 27, 87. Yudkin, J, Trends in Biochemical Sciences, 1976, 1, N126. 2
High serum concentrations of antidepressants in elderly patients
SIR,-We wish to report finding unexpectedly high serum concentrations of amitriptyline and nortriptyline in a small sample of psychiatric inpatients over the age of 60 who were given only modest doses of these drugs. Through the kindness of Dr Braithwaite at the New Cross Hospital Poisons Unit we have been able to monitor amitriptyline and nortriptyline levels regularly on our psychogeriatric unit in blood samples drawn at least 12 hours after drug ingestion. Of about 20 consecutive inpatients studied, five proved to have drug levels well above the therapeutic range currently suggested by this laboratory (80-200 utg/l of nortriptyline and amitriptyline combined). The table printed below gives representative drug levels in these patients, together with dosage and the results of renal function tests. It will be noted that these patients eventually required quite low doses of antidepressant to achieve therapeutic blood levels. The reason is uncertain; renal function was not especially impaired in comparison with other patients of the unit and liver function tests were normal. Ziegler et all also observed unusually high levels in a few patients, but the ages were not given.
SIR,-Your leading article (24 September, p 785) briefly mentions the use of bone scanning in the detection of hypertrophic pulmonary osteoarthropathy (HPOA). Since the differential diagnosis between this condiiton and bony secondaries cannot be made on clinical or laboratory grounds alone a test which can help to solve the issue is relevant, in particular if surgery is proposed as treatment for patients with carcinoma of the bronchus. We have just reviewed 45 cases of carcinoma of the bronchus in which, for staging purposes at first presentation, routine liver and wholebody bone scanning was performed. Seven out of these 45 patients had a positive bone scan and on the basis of this test alone a diagnosis of HPOA was made in two patients. This was particularly useful since bone scanning in these patignts helped to decide on management-in other words, on surgical versus medical treatment. Case 1-A 68-year-old labourer was referred for bronchoscopy. He complained of pain in the left shoulder and upper dorsal spine of six weeks' duration. He had episodes of haemoptysis during the three weeks before admission. A chest radiograph showed a mass at the left hilum with a raised left hemidiaphragm. On examination he had moderate finger clubbing and two small lymph nodes palpable in the left supraclavicular fossa. Bronchoscopy revealed a tumour of the left upper lobe bronchus and histological examination confirmed this to be a type of squamous-cell carcinoma. An intravenous pyelogram was normal and so were radiographs of the shoulders and humeri. On one radiograph partial collapse of a dorsal vertebra was seen associated with osteoporosis. However, secondary bony deposits could not be excluded. Haemoglobin, serum alkaline phosphatase, and liver
99mTc-Imidodiphosphate whole-body bone scan. Intense pericortical uptake is seen involving bilaterally femur and tibia as well as ulna and radius. Typical "streaking" of the radiopharmaceutical is noted. The scan is typical of HPOA and rules out the presence of multiple bony secondaries. These tend to show central rather than pericortical deposition of the radiopharmaceutical with multiple and irregular "hot spots".
enzyme, levels were normal. A 99mTc-imidodiphosphate whole-body bone scan showed typical changes of HPOA. Subsequent follow-up radiographs of the hands, forearms, and tibia and fibula did not show any of the usual radiological features of this condition. Case 2-A 54-year-old brewery worker was referred to us for bronchoscopy. He gave an eight weeks' history of painful and slightly swollen ankles. He had gross finger clubbing and a chest x-ray showed a mass at the apex of the left lower lobe. Bronchoscopy was normal. A raised alkaline phosphatase level suggested the possibility of bone involvement. Skeletal metastases were suspected and a whole-body bone scan was performed with 99mTc-imidodiphosphate. This scan showed typical features of generalised HPOA (see figure), with no evidence of secondary deposits. The patient had an uneventful pneumonectomy with all tumour and a few enlarged hilar glands removed. Alkaline phosphatase levels had not changed two weeks after surgery. Histological examination showed a squamous-cell carcinoma. We conclude that in our series of 45 patients
approximately 10 % (seven patients) with carcinoma of the bronchus had a positive bone scan at the time of first presentation. Of these, two had a bone scan diagnostic of HPOA. This investigation was helpful in
Dosage and plasma concentrations of antidepressants and results of renalfunction tests in five patients Patient
"Sex) A (F) B (F)
Age (years)
Weight (kg)
Plasma urea (mmol ,1)
Creatinine clearance
Single daily dose (at night) (mg)
Plasma levels
(ml/min)
(4.g/1)
Final dose (mg)
77
63 58
95 64
32-43 34-41
(Nort) 100 (Nort) 100
427-600 250
50
76
C (F)
76
55
D (F)
64
43 5
12-19-5
13-16
(Amit) 100
(Amit) 156 (Nort) 62
(Amit) 75
(Amit) 213 (Nort) 245
(Amit) 75
Final plasma levels
(OLgIl) 141
(Amit)
61
(Nort)
39
(Amit) 75
100 (Amit) 117 (Nort) 63
(Amit) 25
(Amit)
218 38
(Nort)
458*
E (M)
64
57
55
48
Nort = Nortriptyline. Amit =Amitriptyline. *Measured 9 h after preceding dose. Conversion: SI to traditional units-Urea: 1 mmol I 6 mg 100 ml.
(Nort) 100
176
75
127
180 53 108 161
BRITISH MEDICAL JOURNAL
1152
ruling out the presence of bony secondaries, confirming the indication for primary surgical treatment. Whole-body bone scanning is easy to perform, non-invasive in nature, takes 30 minutes of the patient's time, and costs approximately £6. It should be routinely performed in the staging of carcinoma of the bronchus. T C STOKES London Chest Hospital, London E2
P J ELL J DEACON Middlesex Hospital Medical School, London Wl
Bacteriology of abscesses of the CNS SIR,-I should like to point out what seems to me to be a misleading impression from a recent article (15 October, p 981). The bacteriology of abscesses in the central nervous system is a sine qua non with regard to the appropriate antibiotic therapy. However, the two main causes of the high mortality in surgically treatable intracranial abscesses remain-namely, (1) delay in diagnosis and (2) failure of accurate localisation.' 2 Enthusiasm for early diagnosis may be dampened by accepting a pessimistic outlook from the start. It is important to emphasise from the point of view of the physician who has primary care of patients suspected of having an intracranial abscess that by computerised tomography an early diagnosis is possible as well as accurate localisation.; 1 A J KEOGH Department of Neurological Surgery, Royal Infirmary, Sheffield
Jefferson, A A, and Keogh, A J, Quarterly Jfournal of Medicine, 1977, 46, 389. Shaw, M D M, and Russell, J A, journal of Neurology, Neurosurgery and Psychiatry, 1977, 40, 214. Keogh, A J, and Berrington, N A, in preparation. Keogh, A J, paper read at meeting of Nederlandse Vereniging van Neurochirugen and Society of British Neurological Surgeons, Amsterdam, 1976.
Surveillance of reactions to new medicines
Work has already been done by Dr R A Johnson2 and at the Queen Elizabeth Hospital, Birmingham, to find ways of warning the doctor before he prescribes a risky drug. Both approaches involve checking the characteristics of the drug against a systematic record of the patient's medical history. A useful further step would be to record symptom information together with the normal prescription details at the time that the prescription is prepared. In this way requirements 3, 4, and 5 above could all be achieved. The symptoms are known to the doctor at the time of prescribing so why throw away this information? The approach is applicable to both new and existing drugs, so matched cohorts would be available for analysis. Doctors' names and addresses and a means to identify their patients would be on file for rapid contact and monitoring. Modern technology can provide simple and relatively cheap ways of doing this. The final requirement remains of finding acceptable low-cost procedures. The Pharmaceutical Systems Research Association is using the resources of the pharmaceutical industry to design a system that meets all the objectives. Any one of the existing proposals would be beneficial in the short term, but only as a step towards a full solution of the drugs problem.
29 OCTOBER 1977
Portojet in giving intradermal doses of influenza vaccine. On the positive side, in difficult circumstances when reactions are likely to be severe or there is a shortage of vaccine, a little protection may be better than no protection at all. I am indebted to Dr M Skirrow of the Worcester Royal Infirmary, for his help with the necessary virological work. D K PAYLER Malvern College,
WXTorcestershire
Antibiotic sprays
SIR,-The article on antibiotic sprays (1 October, p 869) recalls our experience during the invasion of Western Europe. Penicillin was in very short supply and was reserved for those with serious wounds. One batch, however, was found to contain pyrogens and was unsuitable for parenteral use. I managed to get hold of this but the problem was how to issue it to field medical units. Fortunately, throat sprays were available in their equipment and so we issued penicillin tablets which could be dissolved in sterile water immediately before use and the solution sprayed on the skin. The effect was dramatic and hundreds of men with skin sepsis were returned within J A BREWER a day or two to their own units instead of being evacuated to base hospitals and even to Pharmaceutical Systems Research Association, England. This happy result lasted for only Butler, Cox & Partners Ltd a few months until we ran into problems of London EC4 resistant organisms and sensitisation but it Parish, P A, British Medlical Bulletin, 1974, 30, 214. tided us over a difficult period. One great 2 Johnson, R A, paper read at Symposium on IDrug advantage was that a spray resulted in a "noMonitoring in General Practice, Oxford, June 1977. touch" technique and avoided cross infection such as can easily occur when using ointments or creams under difficult conditions. Intradermal influenza vaccine using Portojet 1976 F F HELLIER Leeds
SIR,-In the BMJ (27 November 1976, p 1322) I reported that some 2000 school children and teachers in Malvern had received an 0-15 ml intradermal dose of Admune influenza vaccine using the Portojet vaccinator, with minimal general or localised reactions. In order to check the efficacy of the vaccine 32 volunteers (19 adolescents and 13 adults) gave blood samples immediately before vaccination and three weeks later. Haemagglutination inhibition tests were run in parallel on the paired sera against the New Jersey 1976 strain. The results, which have just become available (see table), were disappointing so far as four-fold rises in antibody titre were concerned, though 44 ° had a titre of more than 1 in 20 after three weeks. The most interesting point arising from the study is that six out of 13 adults already had titres of more than 1 in 20, two having titres of 1 in 160. It was mainly in this group of adults that the four-fold rises occurred. With only one adolescent out of 19 having a fourfold rise it can hardly be said that the intradermal route with the Portojet was successful on this occasion, yet this is at variance with the findings in 1973. More work would be necessary to ascertain the true position of the
Salbutamol-induced ketoacidosis SIR,-I was interested to read the reports of ketoacidosis induced by salbutamol infusion in pregnant diabetics.' 2 We now report hyperglycaemia and ketosis in a non-diabetic patient treated with salbutamol infusion for asthma.
SIR,-The article by Dr A B Wilson (15 October, p 1001) discusses various proposals A 45-year-old woman presented with severe asthma of five days' duration. Pulse was 140'min for monitoring new drugs and makes a new with 45 mm Hg of paradox; peak flow rate proposal that may overcome the shortcomings 50 1,min; arterial blood gases breathing air were: of the others. Both the medical profession and Pao2 4 kPa (30 mm Hg), Paco2 6 kPa (45 mm Hg), the pharmaceutical industry are looking for a pH 7 27. Bililabstix urine testing was normal. method to achieve safer use of drugs. One Prednisone 15 mg six hourly; hydrocortisone characteristic of all the suggestions made so 500 mg six hourly, nebulised salbutamol, fluids far is that they meet the authors' requirements (not dextrose), 35 ¢% oxygen and aminophylline but generally at someone else's expense (for infusion (1 5 mg 'min) produced little improvement example, the patient or the doctor or the and after four hours aminophylline was replaced by salbutamol infusion in increasing doses until pharmacist or the Prescription Pricing 15 tig min was being given. Eight hours after Authority). In designing any kind of system it admission blood gases had progressively improved is sensible to start by identifying the requireto: Pao2 14 kPa (106 mm Hg), Paco2 4 kPa ments to be satisfied. May I suggest the (30 mm Hg), pH 7 36, breathing 35 ', oxygen. following: Sixteen hours after admission, 2 % glycosuria and (1) To maximise the patient's probability of a moderate reaction for ketones were noted, and recovery-this implies that once a product is blood sugar was 12 8 mmol/l, but blood gases and licensed its availability should not be restricted pH were unchanged. Salbutamol infusion rate was by fear of the unknown; (2) to make the doctor aware of foreseeable adverse reactions at the Results of haemagglutination inhibition tests after 0-15 ml intradertnal influienza vaccine time he prescribes the drug, so that he can act responsibly and rationally'; (3) to detect 4-fold rise of Geometric mean Titres of 20 or more HI titre adverse reactions that may occur infrequently; Before After Before After (4) to quantify the extent of such adverse 7 15 6 numbers (32) 225 9 6 14 reactions; (5) to provide a means to contact Total 6 38 5 >30 years (13) 540 8 6 11 patients who may be at risk; (6) to minimise 13-20 I years (19) .. 00 0 0 8 95 3 the additional work and cost for all concerned.
BRITISH MEDICAL JOURNAL
experiments not only to record, the amount of "carbohydrate" but to specify the sort of carbohydrate they have used ? Sucrose produces a very wide range of abnormalities that are not produced by starch.; For example, in the studies referred to in this letter our control animals, which showed no renal abnormalities, were fed exactly similar diets with exactly the same proportion of carbohydrate as were the experimental animals; the difference was only that for the former the dietary carbohydrate was starch and for the latter it was sucrose. K R BRUCKDORFER Royal Free Hospital Medical School, London WCl
1151
These results emphasise the need for caution in prescribing tricyclic antidepressants to elderly patients and once again illustrate the unsuitability of drug dosage as a parameter with which to correlate therapeutic response. Three of the five patients did not in fact suffer side effects of unusual type or severity despite the high levels, but one (B) became ataxic and another (D) suffered a toxic confusional state. Both patients recovered on a reduced dose. A C CARR R P HOBSON Maudsley Hospital, London SE5 Ziegler, V, et al, British Jrournal of Psychiatry, 1977,
131, 168. S S KANG ROBERT G PRICE JOHN YUDKIN Diagnosis of hypertrophic pulmonary
Queen Elizabeth College, London W8
osteoarthropathy
Cohen, A M, and Rosenmann, E, Diabetologia, 1971, 7, 25. Kang, S S, et al, Biochemical Society Transactions, 1977, 5, 235. Kang, S S, et al, Proceedings of the Nutrition Society, 1977, 36, 27A. 4Dance, N, et al, Clinica Chimica Acta, 1970, 27, 87. Yudkin, J, Trends in Biochemical Sciences, 1976, 1, N126. 2
High serum concentrations of antidepressants in elderly patients
SIR,-We wish to report finding unexpectedly high serum concentrations of amitriptyline and nortriptyline in a small sample of psychiatric inpatients over the age of 60 who were given only modest doses of these drugs. Through the kindness of Dr Braithwaite at the New Cross Hospital Poisons Unit we have been able to monitor amitriptyline and nortriptyline levels regularly on our psychogeriatric unit in blood samples drawn at least 12 hours after drug ingestion. Of about 20 consecutive inpatients studied, five proved to have drug levels well above the therapeutic range currently suggested by this laboratory (80-200 utg/l of nortriptyline and amitriptyline combined). The table printed below gives representative drug levels in these patients, together with dosage and the results of renal function tests. It will be noted that these patients eventually required quite low doses of antidepressant to achieve therapeutic blood levels. The reason is uncertain; renal function was not especially impaired in comparison with other patients of the unit and liver function tests were normal. Ziegler et all also observed unusually high levels in a few patients, but the ages were not given.
SIR,-Your leading article (24 September, p 785) briefly mentions the use of bone scanning in the detection of hypertrophic pulmonary osteoarthropathy (HPOA). Since the differential diagnosis between this condiiton and bony secondaries cannot be made on clinical or laboratory grounds alone a test which can help to solve the issue is relevant, in particular if surgery is proposed as treatment for patients with carcinoma of the bronchus. We have just reviewed 45 cases of carcinoma of the bronchus in which, for staging purposes at first presentation, routine liver and wholebody bone scanning was performed. Seven out of these 45 patients had a positive bone scan and on the basis of this test alone a diagnosis of HPOA was made in two patients. This was particularly useful since bone scanning in these patignts helped to decide on management-in other words, on surgical versus medical treatment. Case 1-A 68-year-old labourer was referred for bronchoscopy. He complained of pain in the left shoulder and upper dorsal spine of six weeks' duration. He had episodes of haemoptysis during the three weeks before admission. A chest radiograph showed a mass at the left hilum with a raised left hemidiaphragm. On examination he had moderate finger clubbing and two small lymph nodes palpable in the left supraclavicular fossa. Bronchoscopy revealed a tumour of the left upper lobe bronchus and histological examination confirmed this to be a type of squamous-cell carcinoma. An intravenous pyelogram was normal and so were radiographs of the shoulders and humeri. On one radiograph partial collapse of a dorsal vertebra was seen associated with osteoporosis. However, secondary bony deposits could not be excluded. Haemoglobin, serum alkaline phosphatase, and liver
99mTc-Imidodiphosphate whole-body bone scan. Intense pericortical uptake is seen involving bilaterally femur and tibia as well as ulna and radius. Typical "streaking" of the radiopharmaceutical is noted. The scan is typical of HPOA and rules out the presence of multiple bony secondaries. These tend to show central rather than pericortical deposition of the radiopharmaceutical with multiple and irregular "hot spots".
enzyme, levels were normal. A 99mTc-imidodiphosphate whole-body bone scan showed typical changes of HPOA. Subsequent follow-up radiographs of the hands, forearms, and tibia and fibula did not show any of the usual radiological features of this condition. Case 2-A 54-year-old brewery worker was referred to us for bronchoscopy. He gave an eight weeks' history of painful and slightly swollen ankles. He had gross finger clubbing and a chest x-ray showed a mass at the apex of the left lower lobe. Bronchoscopy was normal. A raised alkaline phosphatase level suggested the possibility of bone involvement. Skeletal metastases were suspected and a whole-body bone scan was performed with 99mTc-imidodiphosphate. This scan showed typical features of generalised HPOA (see figure), with no evidence of secondary deposits. The patient had an uneventful pneumonectomy with all tumour and a few enlarged hilar glands removed. Alkaline phosphatase levels had not changed two weeks after surgery. Histological examination showed a squamous-cell carcinoma. We conclude that in our series of 45 patients
approximately 10 % (seven patients) with carcinoma of the bronchus had a positive bone scan at the time of first presentation. Of these, two had a bone scan diagnostic of HPOA. This investigation was helpful in
Dosage and plasma concentrations of antidepressants and results of renalfunction tests in five patients Patient
"Sex) A (F) B (F)
Age (years)
Weight (kg)
Plasma urea (mmol ,1)
Creatinine clearance
Single daily dose (at night) (mg)
Plasma levels
(ml/min)
(4.g/1)
Final dose (mg)
77
63 58
95 64
32-43 34-41
(Nort) 100 (Nort) 100
427-600 250
50
76
C (F)
76
55
D (F)
64
43 5
12-19-5
13-16
(Amit) 100
(Amit) 156 (Nort) 62
(Amit) 75
(Amit) 213 (Nort) 245
(Amit) 75
Final plasma levels
(OLgIl) 141
(Amit)
61
(Nort)
39
(Amit) 75
100 (Amit) 117 (Nort) 63
(Amit) 25
(Amit)
218 38
(Nort)
458*
E (M)
64
57
55
48
Nort = Nortriptyline. Amit =Amitriptyline. *Measured 9 h after preceding dose. Conversion: SI to traditional units-Urea: 1 mmol I 6 mg 100 ml.
(Nort) 100
176
75
127
180 53 108 161
BRITISH MEDICAL JOURNAL
1152
ruling out the presence of bony secondaries, confirming the indication for primary surgical treatment. Whole-body bone scanning is easy to perform, non-invasive in nature, takes 30 minutes of the patient's time, and costs approximately £6. It should be routinely performed in the staging of carcinoma of the bronchus. T C STOKES London Chest Hospital, London E2
P J ELL J DEACON Middlesex Hospital Medical School, London Wl
Bacteriology of abscesses of the CNS SIR,-I should like to point out what seems to me to be a misleading impression from a recent article (15 October, p 981). The bacteriology of abscesses in the central nervous system is a sine qua non with regard to the appropriate antibiotic therapy. However, the two main causes of the high mortality in surgically treatable intracranial abscesses remain-namely, (1) delay in diagnosis and (2) failure of accurate localisation.' 2 Enthusiasm for early diagnosis may be dampened by accepting a pessimistic outlook from the start. It is important to emphasise from the point of view of the physician who has primary care of patients suspected of having an intracranial abscess that by computerised tomography an early diagnosis is possible as well as accurate localisation.; 1 A J KEOGH Department of Neurological Surgery, Royal Infirmary, Sheffield
Jefferson, A A, and Keogh, A J, Quarterly Jfournal of Medicine, 1977, 46, 389. Shaw, M D M, and Russell, J A, journal of Neurology, Neurosurgery and Psychiatry, 1977, 40, 214. Keogh, A J, and Berrington, N A, in preparation. Keogh, A J, paper read at meeting of Nederlandse Vereniging van Neurochirugen and Society of British Neurological Surgeons, Amsterdam, 1976.
Surveillance of reactions to new medicines
Work has already been done by Dr R A Johnson2 and at the Queen Elizabeth Hospital, Birmingham, to find ways of warning the doctor before he prescribes a risky drug. Both approaches involve checking the characteristics of the drug against a systematic record of the patient's medical history. A useful further step would be to record symptom information together with the normal prescription details at the time that the prescription is prepared. In this way requirements 3, 4, and 5 above could all be achieved. The symptoms are known to the doctor at the time of prescribing so why throw away this information? The approach is applicable to both new and existing drugs, so matched cohorts would be available for analysis. Doctors' names and addresses and a means to identify their patients would be on file for rapid contact and monitoring. Modern technology can provide simple and relatively cheap ways of doing this. The final requirement remains of finding acceptable low-cost procedures. The Pharmaceutical Systems Research Association is using the resources of the pharmaceutical industry to design a system that meets all the objectives. Any one of the existing proposals would be beneficial in the short term, but only as a step towards a full solution of the drugs problem.
29 OCTOBER 1977
Portojet in giving intradermal doses of influenza vaccine. On the positive side, in difficult circumstances when reactions are likely to be severe or there is a shortage of vaccine, a little protection may be better than no protection at all. I am indebted to Dr M Skirrow of the Worcester Royal Infirmary, for his help with the necessary virological work. D K PAYLER Malvern College,
WXTorcestershire
Antibiotic sprays
SIR,-The article on antibiotic sprays (1 October, p 869) recalls our experience during the invasion of Western Europe. Penicillin was in very short supply and was reserved for those with serious wounds. One batch, however, was found to contain pyrogens and was unsuitable for parenteral use. I managed to get hold of this but the problem was how to issue it to field medical units. Fortunately, throat sprays were available in their equipment and so we issued penicillin tablets which could be dissolved in sterile water immediately before use and the solution sprayed on the skin. The effect was dramatic and hundreds of men with skin sepsis were returned within J A BREWER a day or two to their own units instead of being evacuated to base hospitals and even to Pharmaceutical Systems Research Association, England. This happy result lasted for only Butler, Cox & Partners Ltd a few months until we ran into problems of London EC4 resistant organisms and sensitisation but it Parish, P A, British Medlical Bulletin, 1974, 30, 214. tided us over a difficult period. One great 2 Johnson, R A, paper read at Symposium on IDrug advantage was that a spray resulted in a "noMonitoring in General Practice, Oxford, June 1977. touch" technique and avoided cross infection such as can easily occur when using ointments or creams under difficult conditions. Intradermal influenza vaccine using Portojet 1976 F F HELLIER Leeds
SIR,-In the BMJ (27 November 1976, p 1322) I reported that some 2000 school children and teachers in Malvern had received an 0-15 ml intradermal dose of Admune influenza vaccine using the Portojet vaccinator, with minimal general or localised reactions. In order to check the efficacy of the vaccine 32 volunteers (19 adolescents and 13 adults) gave blood samples immediately before vaccination and three weeks later. Haemagglutination inhibition tests were run in parallel on the paired sera against the New Jersey 1976 strain. The results, which have just become available (see table), were disappointing so far as four-fold rises in antibody titre were concerned, though 44 ° had a titre of more than 1 in 20 after three weeks. The most interesting point arising from the study is that six out of 13 adults already had titres of more than 1 in 20, two having titres of 1 in 160. It was mainly in this group of adults that the four-fold rises occurred. With only one adolescent out of 19 having a fourfold rise it can hardly be said that the intradermal route with the Portojet was successful on this occasion, yet this is at variance with the findings in 1973. More work would be necessary to ascertain the true position of the
Salbutamol-induced ketoacidosis SIR,-I was interested to read the reports of ketoacidosis induced by salbutamol infusion in pregnant diabetics.' 2 We now report hyperglycaemia and ketosis in a non-diabetic patient treated with salbutamol infusion for asthma.
SIR,-The article by Dr A B Wilson (15 October, p 1001) discusses various proposals A 45-year-old woman presented with severe asthma of five days' duration. Pulse was 140'min for monitoring new drugs and makes a new with 45 mm Hg of paradox; peak flow rate proposal that may overcome the shortcomings 50 1,min; arterial blood gases breathing air were: of the others. Both the medical profession and Pao2 4 kPa (30 mm Hg), Paco2 6 kPa (45 mm Hg), the pharmaceutical industry are looking for a pH 7 27. Bililabstix urine testing was normal. method to achieve safer use of drugs. One Prednisone 15 mg six hourly; hydrocortisone characteristic of all the suggestions made so 500 mg six hourly, nebulised salbutamol, fluids far is that they meet the authors' requirements (not dextrose), 35 ¢% oxygen and aminophylline but generally at someone else's expense (for infusion (1 5 mg 'min) produced little improvement example, the patient or the doctor or the and after four hours aminophylline was replaced by salbutamol infusion in increasing doses until pharmacist or the Prescription Pricing 15 tig min was being given. Eight hours after Authority). In designing any kind of system it admission blood gases had progressively improved is sensible to start by identifying the requireto: Pao2 14 kPa (106 mm Hg), Paco2 4 kPa ments to be satisfied. May I suggest the (30 mm Hg), pH 7 36, breathing 35 ', oxygen. following: Sixteen hours after admission, 2 % glycosuria and (1) To maximise the patient's probability of a moderate reaction for ketones were noted, and recovery-this implies that once a product is blood sugar was 12 8 mmol/l, but blood gases and licensed its availability should not be restricted pH were unchanged. Salbutamol infusion rate was by fear of the unknown; (2) to make the doctor aware of foreseeable adverse reactions at the Results of haemagglutination inhibition tests after 0-15 ml intradertnal influienza vaccine time he prescribes the drug, so that he can act responsibly and rationally'; (3) to detect 4-fold rise of Geometric mean Titres of 20 or more HI titre adverse reactions that may occur infrequently; Before After Before After (4) to quantify the extent of such adverse 7 15 6 numbers (32) 225 9 6 14 reactions; (5) to provide a means to contact Total 6 38 5 >30 years (13) 540 8 6 11 patients who may be at risk; (6) to minimise 13-20 I years (19) .. 00 0 0 8 95 3 the additional work and cost for all concerned.
