- Email: [email protected]
ALLOPURINOL MODULATION OF HIGH-DOSE FLUOROURACIL TOXICITY
1353
teaching that not every "underweight" child is suffering (currently) from malnutrition or that the slope of the weight curve is the best indicator of weight status; but the evaluation it allows of the child’s present weight is especially valuable when, often in developing countries, there are insufficient points the graph to make a meaningful curve. Together with simple clinical signs for lack of muscle and subcutaneous fat, the classification helps establish definite criteria for the diagnosis of the different degrees and types of malnutrition and for the action the P.H.c.w. needs to take.s Length/height assessment will not be feasible as a routine at the primary level in many developing countries. (3) The Wellcome classification is useful in the nutritional evaluation of communities6-s and the simple data it generates can be supplemented if need be.6 The use of the same system in individual and in community assessment9 helps P.H.C.W.S to understand the links between the clinical and epidemiological aspects of the problem, and the charts then promote the execution by P.H.C.W.S of community actions needed at the primary level.’° This may prove to be the most important use of growth charts in the long run. (4) The system permits the ongoing collection of simple nutritional statistics9 which P.H.C.W.S can readily understand and use to monitor their community activities. (5) With regard to international standardisation the W.H.O. guidelines report that most growth charts studied from around the world used a system of percentage classification of weight deficit. The blank section on the W.H.O. chart for "reasons for special care" implies that the P.H.C.W.S will be able to fill in risk factors without a memory aid; often this will not be so. The Mozambican chart has the most common risk factors printed as checklists near the weight graph. Those factors which apply in the longer term (often from birth) have to be ticked. Those which apply more at specific times are to be written in the column of the appropriate month. as so
on
Mother and Child Health
of lifts. Their intra-abdominal pressure was measured with an intragastric pressure transducer mounted on a fine catheter (Gaeltec). An attempt was made to measure the degree of pain increase caused by the lifts on a verbal scale ranging from 0 (no pain increase) to 10 (the worst possible pain increase imaginable.4 In the back-pain group, the painful lifts produced significantly higher pressure rises than did the painless lifts (factor analysis P<0.01) and the controls (P<0.01). There was no significant difference between the painless lifts and the controls. The pressure rise was plotted against the pain scale for various groups of lift. These demonstrated some correlation between the pressure rise and the perceived pain: 5 kg lifts with the arms 50% extended (R=0.24 ; p<0.05); 5 kg lifts with the arms 100% extended (R=0.36 ; r<005); and forward thrust with the arms 100% extended (R=0-36; P<0.05). The evidence suggests that this pressure rise may be related to low back pain and therefore may be used as a method of objectively measuring that pain. These results, which will be reported in full elsewhere, emphasise the physiological importance of the abdomen in supporting the lumbar spine. Department for Spinal Disorders, Institute of Orthopædics, Robert Jones and Agnes Hunt Orthopædic Hospital, Oswestry, Shropshire SY10 7AG
JEREMY C. T. FAIRBANK JOHN P. O’BRIEN
Department of Human Biology and Health, University of Surrey
P. R. DAVIS
Section,
Ministry of Health, Maputo, Mozambique *Present address: Institute of
MALCOLM SEGALL* Development Studies, University
of
Sussex,
Brighton. INTRA-ABDOMINAL PRESSURE AND LOW BACK PAIN
SIR,-In chronic pain, and specifically with spinal pain, a rational and objective method of measurement of back pain has remained elusive. This has contributed to making back pain one of the most ignored and least understood pain syndromes in clinical science. The rise in intra-abdominal pressure during lifting is directly related to the theoretical load on the lumbar spine.1-3 There are essentially two mechanisms for resisting stresses on the lumbar spine-a musculoskeletal mechanism and a pneumatic mechanism, formed by the abdominal cavity. If one mechanism is interfered with the other might take over some of the strain. Patients who have recently had a laparotomy, produce lower than expected abdominal pressure rises during lifting (D. A. Stubbs, personal communication). Patients with 5. O
painful backs might be expected to have a higher than anticipated pressure rise. Further, the pressure rise may relate to the amount of pain the lift causes. These hypotheses were tested on 23 patients with chronic low back pain and on 12 normal controls. All were males aged 20-54 years. They were asked to perform a series of thirteen lifts of 5 and 10 kg weights in various directions. 22 of the 23 patients experienced increased pain in at least one of the series
Programa de Proteccao Materno-Infantile; technical annexes I & II. Ministry of Health, Mozambique, Maputo (in the press). 6. Waterlow, J. C. Br. med. J. 1972, iii, 566. 7. Eddy, T. P. Trop. Doctor, 1977, 7, 28. 8. Techniques d’enquete nutritionnelle rapide dans les villages (document AFR/ NUT/84). W.H.O. Regional Office for Africa, Brazzaville, 1977. 9. Bailey, K. V. Manual on Public Health Nutrition. W.H.O. Regional Office for Africa, Brazzaville, 1975. 10. Lessoins de santé primaires au Mozambique: official document presented at the W.H.O./UNICEF conference on primary health care at Alma Ata in September 1978. Ministry of Health, Mozambique, Maputo, 1978. 1. Davis, P. R. J. Anat., Lond. 1956, 90, 601. 2. Morris, J. M., Lucas, D. B., Bresler, E. J. Bone Jt Surg. 1961, 43A, 327. 3. Andersson, G. B. J., Ortengren, R., Nachemson, A. Spine, 1976, 1, 178.
ALLOPURINOL MODULATION OF HIGH-DOSE FLUOROURACIL TOXICITY
SIR,-The letter by Dr Fox and his colleagues (March 24, 677) has very important implications for all who use 5-fluorouracil (5-FU) in treating patients with malignancies. Fox et p.
al. suggest that the fact that tumour responses to 5-FU are in patients demonstrating drug toxicity points to the presence of a steep dose-response curve. Oxypurinol, the active in-vivo metabolite of allopurinol, inhibits orotate (pyrimore common
midine) phosphoribosyltransferase (PRPP transferase) and thymidine phosphorylase, two of the three enzymes which activate 5-FU, and Fox et al. go on to suggest that co-administration of allopurinol with 5-FU would in some way protect patients against 5-FU toxicity without interfering with 5-FU tumour-cell killing. We would argue that co-administration of allopurinol with 5-FU would preferentially protect tumour cells, not normal host cells, against the toxicity of 5-FU. This point is supported by the following:
(a) Nahas and Hall’ have demonstrated that, for the most part, 5-FU-sensitive colon carcinoma cells contain high levels of PRPP transferase, more so than do the normal surrounding colonic mucosal cells. These workers found that in-vivo 5-FU responses of human colon cancer were more common in tumours that contained higher PRPP transferase levels than in the surrounding colonic mucosal cells. If PRPP transferase were blocked by allopurinol, as Fox el al. suggest, tumour-cell kill by 5-FU should be adversely affected. (b) Since the availability of phosphoribosylpyrophosphate (PRPP) may be an important factor in 5-FU activation, then one would expect that any drug which would tend to utilize PRPP itself (i.e., oxypurinol) or inhibit its synthesis (i.e., oxypurinol) would be antagonistic to 4. Woodeforde, J. M., Merskey, H. J. psychosom. Res. 1972, 16, 173. 1. Nahas, A. L. Y., Savlov, E. D., Hall, T. C. Cancer Chemother. part I, 58, 909.
Rep. 1974,
1354 cells that have higher levels of the enzyme that uses PRPP. Hochstein and Utley2 have suggested that xanthine oxidase, which is inhibited by oxypurinol, may have a positive feedback influence on purine nucleotide synthesis by inhibiting a complex linkage between xanthine conversion to uric acid, which in turn generates 6-phosphogluconate from glucose-6-phosphate, yielding PRPP as the end product. (c) To add clinical evidence to the possible importance of PRPP transferase activity and the quantity of intracellular PRPP, we have noted that prior administration of methotrexate (a drug inhibiting the utilisation of PRPP for purine synthesis, thereby raising intracellular PRPP levels; Dr Edward Cadman personal communication) before treatment with 5-FU caused five of seven responses in metastatic adenocarcinoma of the colon. We attributed these responses to the possible enhancement of the PRPP transferase activation of 5-FU in colon tumour cells. Such would be consistent with the data of Nahas and Hall. tumour
The data presented by Fox et al., however, are very important because these workers found that four of ten patients with colorectal cancer had objective tumour regression after receiving a continuous infusion of 5-FU 2 or more g/m2/day 5 days. Since this amount of 5-FU is higher than that generally used, we would expect that their good tumour responses are due to the high doses of 5-FU which may have overcome allopurinol protection of colon tumour cells. In our studies with methotrexate and 5-FU we used doses of 5-FU equal to 1500 mg/m2 once every 3-4 weeks. 5-FU was given as a single bolus one hour after a large bolus of methotrexate, which we argued, would increase intracellular PRPP levels and force 5-FU into an activated state which would subsequently cause higher levels of FDUMP and also possibly push more 5-FU into tumour cell RNA.3 Perhaps Fox et al. should compare large doses of 5-FU alone versus concomitant administration with allopurinol, since it is quite possible that they are simply seeing better response-rates to higher doses of 5-FU. We would predict that allopurinol would inhibit the anti-tumour activity of S-FU. Since 5-FU is usually used at doses much lower than 2 g/m2/day 5 days, coadministration of allopurinol in an attempt to avert 5-FU toxicity might drastically lower (and, possibly, entirely negate) any beneficial anti-tumour response to 5-FU. GLENN TISMAN SHOW JEN GRACE WU
2101 West Beverly Boulevard, Montebello, California 90640, U.S.A
RISK MARKER FOR WERNICKE’S ENCEPHALOPATHY
SiR,-Your editorial of May 26
on Wernicke’s encephalowish for a risk marker for individuals simple pathy expresses susceptible to this illness. I believe that Blass and Gibson’ provided this when they found that transketolase in fibroblasts from patients with Wernicke-Korsakoff syndrome bound thiamine pyrophosphate less avidly than normal. The patients seem to have an inborn error of metabolism that is clinically important only when the diet is inadequate in thiamine. a
V.A. Hospital, North Chicago, Illinois 60064, U.S.A. and Department of Psychiatry, Chicago Medical School
SIR,-Acute epiglottitis, which is almost invariably caused by Haemophilus influenzae type b, is a life-threatening infection can
2. Hochstem,
affect adults
as
agar.2 Although
a good result was achieved in this case, it is possible that the response would have been less rapid if the isolate had been more resistant to ampicillin; some ampicillin-resistant strains of H. influenzce type b have an m.i.c. as great as 50 fLg/ml with a moderate inoculum. We suggest that chemotherapy in epiglottitis and in hxmophilus meningitis should begin with ampicillin and chloramphenicol in combination. Since 1974 ampicillin-resistant strains of H. influenzce type b have been isolated from children with meningitis5 and a chloramphenicol-resistant strain of H. influenzae type b causing meningitis has been reported.6 When antibiotic sensitivity tests have been done one of the two drugs can be withdrawn. Should strains of H. influenzx type b emerge which are resistant to both ampicillin and chloramphenicol, alternative drugs, such as co-trimoxazole will need to be considered. Although an aminoglycoside, especially gentamicin or tobramycin, could be useful in epiglottitis, the limited penetration of these drugs into cerebrospinal fluid would render them of doubtful value in meningitis.
I thank Dr Hugh Douglas and Dr Thomas Allen for their approval the case-notes of their patient, and Mr Andrew Moore for his
to use
technical assistance.
Microbiology Department, Adelaide Children’s Hospital, North Adelaide, South Australia 5006
well
as
children. Skilled
nasotra-
P., Utley, H. Mol. Pharmac. 1978, 4, 572. 3. Tisman, G., Wu, S. J. G. Proceedings of Second International Conference on Adjuvant Therapy of Cancer, 1979; abstr. 1. Blass, J. P., Gibson, G. E. New Engl. J. Med. 1977, 297, 1367.
DAVID HANSMAN
GLUCAGON AND INSULIN IN PANCREATIC EXOCRINE SECRETIONS
R. K. NADELLA
AMPICILLIN-INSENSITIVE HÆMOPHILUS INFLUENZÆ TYPE B CAUSING ACUTE EPIGLOTTITIS
which
cheal intubation’ and suitable chemotherapy are the keystones in management-intubation to relieve respiratory obstruction and chemotherapy to halt the bactersemia and so prevent infective complications, especially pneumonia, meningitis, and arthritis. In this hospital we have seen a child with epiglottitis in whom blood culture yielded an ampicillin-insensitive strain of H. influenzae type b. This was a girl aged 2 years and 11 months who presented on Oct. 27, 1978, with anorexia and fever of 1 day’s duration, followed by increasing respiratory distress. She was mildly febrile (37’4°C) and her epiglottis was reddened and swollen. A blood-sample for culture was collected, and the child was intubated and ampicillin administered intravenously at a dose of 200 mg/kg/day in four equally divided doses. There was a rapid improvement: within 24 h she was afebrile and could be extubated. Ampicillin was stopped after 48 h and replaced with amoxycillin orally in a dose of 50 mg/kg/day. H. influenzae type b was isolated from the blood culture; on disc diffusion testing2 the strain was insensitive to ampicillin (2 pLg) and tests for p-lactamaselyielded a positive result; the isolate was sensitive to chloramphenicol (10 ug), tetracycline (10 ug), trimethoprim (1.25 tg), and co-trimoxazole (25 tg). With the moderate inoculum of 1000 viable units the minimal inhibitory concentration (M.iC.) was 2.0 p.g ampicillin per ml, whereas an ampicillin-sensitive strain of H. influenzce type b tested as a control showed a mt.i.c. of 0.5 g per ml; tests were done by plate titration on heated blood
SIR,-Carr-Locke and Track’ found significant amounts of human pancreatic polypeptide (PP) in pancreatic juice obtained during cannulation of the papilla of Vater. Since others8 had noted that intravenous administration of PP 1.
Sweeney,
D.
B., Allen,
T.
H., Steven, I. M. Anœsth. intens. Care, 1973, 1,
526.
Hansman, D. Lancet, 1975, ii, 893. Perret, C. J. Nature, 1954, 174, 1012. Slack, M. P. E., Wheldon, D. B., Turk, D. C. Lancet, 1977, ii, 906. 5. Tomeh, M. O., Starr, S. E., McGowan, J. E., Terry, P. M., Nahmias, A J. J. Am. med. Ass. 1974, 229, 295. 6. Kinmonth, A. L., Storrs, C. N., Mitchell, R. G. Br. med. J. 1978, i, 694. 7. Carr-Locke, D. L., Track, N. S., Lancet, 1979, i, 151. 8. Greenberg, G. R., McCloy, R. F., Adrian, T. E., Chadwick, V. S., Baron, J. H., Bloom, S. R. ibid. 1978, ii, 1280.
2. 3. 4.
teaching that not every "underweight" child is suffering (currently) from malnutrition or that the slope of the weight curve is the best indicator of weight status; but the evaluation it allows of the child’s present weight is especially valuable when, often in developing countries, there are insufficient points the graph to make a meaningful curve. Together with simple clinical signs for lack of muscle and subcutaneous fat, the classification helps establish definite criteria for the diagnosis of the different degrees and types of malnutrition and for the action the P.H.c.w. needs to take.s Length/height assessment will not be feasible as a routine at the primary level in many developing countries. (3) The Wellcome classification is useful in the nutritional evaluation of communities6-s and the simple data it generates can be supplemented if need be.6 The use of the same system in individual and in community assessment9 helps P.H.C.W.S to understand the links between the clinical and epidemiological aspects of the problem, and the charts then promote the execution by P.H.C.W.S of community actions needed at the primary level.’° This may prove to be the most important use of growth charts in the long run. (4) The system permits the ongoing collection of simple nutritional statistics9 which P.H.C.W.S can readily understand and use to monitor their community activities. (5) With regard to international standardisation the W.H.O. guidelines report that most growth charts studied from around the world used a system of percentage classification of weight deficit. The blank section on the W.H.O. chart for "reasons for special care" implies that the P.H.C.W.S will be able to fill in risk factors without a memory aid; often this will not be so. The Mozambican chart has the most common risk factors printed as checklists near the weight graph. Those factors which apply in the longer term (often from birth) have to be ticked. Those which apply more at specific times are to be written in the column of the appropriate month. as so
on
Mother and Child Health
of lifts. Their intra-abdominal pressure was measured with an intragastric pressure transducer mounted on a fine catheter (Gaeltec). An attempt was made to measure the degree of pain increase caused by the lifts on a verbal scale ranging from 0 (no pain increase) to 10 (the worst possible pain increase imaginable.4 In the back-pain group, the painful lifts produced significantly higher pressure rises than did the painless lifts (factor analysis P<0.01) and the controls (P<0.01). There was no significant difference between the painless lifts and the controls. The pressure rise was plotted against the pain scale for various groups of lift. These demonstrated some correlation between the pressure rise and the perceived pain: 5 kg lifts with the arms 50% extended (R=0.24 ; p<0.05); 5 kg lifts with the arms 100% extended (R=0.36 ; r<005); and forward thrust with the arms 100% extended (R=0-36; P<0.05). The evidence suggests that this pressure rise may be related to low back pain and therefore may be used as a method of objectively measuring that pain. These results, which will be reported in full elsewhere, emphasise the physiological importance of the abdomen in supporting the lumbar spine. Department for Spinal Disorders, Institute of Orthopædics, Robert Jones and Agnes Hunt Orthopædic Hospital, Oswestry, Shropshire SY10 7AG
JEREMY C. T. FAIRBANK JOHN P. O’BRIEN
Department of Human Biology and Health, University of Surrey
P. R. DAVIS
Section,
Ministry of Health, Maputo, Mozambique *Present address: Institute of
MALCOLM SEGALL* Development Studies, University
of
Sussex,
Brighton. INTRA-ABDOMINAL PRESSURE AND LOW BACK PAIN
SIR,-In chronic pain, and specifically with spinal pain, a rational and objective method of measurement of back pain has remained elusive. This has contributed to making back pain one of the most ignored and least understood pain syndromes in clinical science. The rise in intra-abdominal pressure during lifting is directly related to the theoretical load on the lumbar spine.1-3 There are essentially two mechanisms for resisting stresses on the lumbar spine-a musculoskeletal mechanism and a pneumatic mechanism, formed by the abdominal cavity. If one mechanism is interfered with the other might take over some of the strain. Patients who have recently had a laparotomy, produce lower than expected abdominal pressure rises during lifting (D. A. Stubbs, personal communication). Patients with 5. O
painful backs might be expected to have a higher than anticipated pressure rise. Further, the pressure rise may relate to the amount of pain the lift causes. These hypotheses were tested on 23 patients with chronic low back pain and on 12 normal controls. All were males aged 20-54 years. They were asked to perform a series of thirteen lifts of 5 and 10 kg weights in various directions. 22 of the 23 patients experienced increased pain in at least one of the series
Programa de Proteccao Materno-Infantile; technical annexes I & II. Ministry of Health, Mozambique, Maputo (in the press). 6. Waterlow, J. C. Br. med. J. 1972, iii, 566. 7. Eddy, T. P. Trop. Doctor, 1977, 7, 28. 8. Techniques d’enquete nutritionnelle rapide dans les villages (document AFR/ NUT/84). W.H.O. Regional Office for Africa, Brazzaville, 1977. 9. Bailey, K. V. Manual on Public Health Nutrition. W.H.O. Regional Office for Africa, Brazzaville, 1975. 10. Lessoins de santé primaires au Mozambique: official document presented at the W.H.O./UNICEF conference on primary health care at Alma Ata in September 1978. Ministry of Health, Mozambique, Maputo, 1978. 1. Davis, P. R. J. Anat., Lond. 1956, 90, 601. 2. Morris, J. M., Lucas, D. B., Bresler, E. J. Bone Jt Surg. 1961, 43A, 327. 3. Andersson, G. B. J., Ortengren, R., Nachemson, A. Spine, 1976, 1, 178.
ALLOPURINOL MODULATION OF HIGH-DOSE FLUOROURACIL TOXICITY
SIR,-The letter by Dr Fox and his colleagues (March 24, 677) has very important implications for all who use 5-fluorouracil (5-FU) in treating patients with malignancies. Fox et p.
al. suggest that the fact that tumour responses to 5-FU are in patients demonstrating drug toxicity points to the presence of a steep dose-response curve. Oxypurinol, the active in-vivo metabolite of allopurinol, inhibits orotate (pyrimore common
midine) phosphoribosyltransferase (PRPP transferase) and thymidine phosphorylase, two of the three enzymes which activate 5-FU, and Fox et al. go on to suggest that co-administration of allopurinol with 5-FU would in some way protect patients against 5-FU toxicity without interfering with 5-FU tumour-cell killing. We would argue that co-administration of allopurinol with 5-FU would preferentially protect tumour cells, not normal host cells, against the toxicity of 5-FU. This point is supported by the following:
(a) Nahas and Hall’ have demonstrated that, for the most part, 5-FU-sensitive colon carcinoma cells contain high levels of PRPP transferase, more so than do the normal surrounding colonic mucosal cells. These workers found that in-vivo 5-FU responses of human colon cancer were more common in tumours that contained higher PRPP transferase levels than in the surrounding colonic mucosal cells. If PRPP transferase were blocked by allopurinol, as Fox el al. suggest, tumour-cell kill by 5-FU should be adversely affected. (b) Since the availability of phosphoribosylpyrophosphate (PRPP) may be an important factor in 5-FU activation, then one would expect that any drug which would tend to utilize PRPP itself (i.e., oxypurinol) or inhibit its synthesis (i.e., oxypurinol) would be antagonistic to 4. Woodeforde, J. M., Merskey, H. J. psychosom. Res. 1972, 16, 173. 1. Nahas, A. L. Y., Savlov, E. D., Hall, T. C. Cancer Chemother. part I, 58, 909.
Rep. 1974,
1354 cells that have higher levels of the enzyme that uses PRPP. Hochstein and Utley2 have suggested that xanthine oxidase, which is inhibited by oxypurinol, may have a positive feedback influence on purine nucleotide synthesis by inhibiting a complex linkage between xanthine conversion to uric acid, which in turn generates 6-phosphogluconate from glucose-6-phosphate, yielding PRPP as the end product. (c) To add clinical evidence to the possible importance of PRPP transferase activity and the quantity of intracellular PRPP, we have noted that prior administration of methotrexate (a drug inhibiting the utilisation of PRPP for purine synthesis, thereby raising intracellular PRPP levels; Dr Edward Cadman personal communication) before treatment with 5-FU caused five of seven responses in metastatic adenocarcinoma of the colon. We attributed these responses to the possible enhancement of the PRPP transferase activation of 5-FU in colon tumour cells. Such would be consistent with the data of Nahas and Hall. tumour
The data presented by Fox et al., however, are very important because these workers found that four of ten patients with colorectal cancer had objective tumour regression after receiving a continuous infusion of 5-FU 2 or more g/m2/day 5 days. Since this amount of 5-FU is higher than that generally used, we would expect that their good tumour responses are due to the high doses of 5-FU which may have overcome allopurinol protection of colon tumour cells. In our studies with methotrexate and 5-FU we used doses of 5-FU equal to 1500 mg/m2 once every 3-4 weeks. 5-FU was given as a single bolus one hour after a large bolus of methotrexate, which we argued, would increase intracellular PRPP levels and force 5-FU into an activated state which would subsequently cause higher levels of FDUMP and also possibly push more 5-FU into tumour cell RNA.3 Perhaps Fox et al. should compare large doses of 5-FU alone versus concomitant administration with allopurinol, since it is quite possible that they are simply seeing better response-rates to higher doses of 5-FU. We would predict that allopurinol would inhibit the anti-tumour activity of S-FU. Since 5-FU is usually used at doses much lower than 2 g/m2/day 5 days, coadministration of allopurinol in an attempt to avert 5-FU toxicity might drastically lower (and, possibly, entirely negate) any beneficial anti-tumour response to 5-FU. GLENN TISMAN SHOW JEN GRACE WU
2101 West Beverly Boulevard, Montebello, California 90640, U.S.A
RISK MARKER FOR WERNICKE’S ENCEPHALOPATHY
SiR,-Your editorial of May 26
on Wernicke’s encephalowish for a risk marker for individuals simple pathy expresses susceptible to this illness. I believe that Blass and Gibson’ provided this when they found that transketolase in fibroblasts from patients with Wernicke-Korsakoff syndrome bound thiamine pyrophosphate less avidly than normal. The patients seem to have an inborn error of metabolism that is clinically important only when the diet is inadequate in thiamine. a
V.A. Hospital, North Chicago, Illinois 60064, U.S.A. and Department of Psychiatry, Chicago Medical School
SIR,-Acute epiglottitis, which is almost invariably caused by Haemophilus influenzae type b, is a life-threatening infection can
2. Hochstem,
affect adults
as
agar.2 Although
a good result was achieved in this case, it is possible that the response would have been less rapid if the isolate had been more resistant to ampicillin; some ampicillin-resistant strains of H. influenzce type b have an m.i.c. as great as 50 fLg/ml with a moderate inoculum. We suggest that chemotherapy in epiglottitis and in hxmophilus meningitis should begin with ampicillin and chloramphenicol in combination. Since 1974 ampicillin-resistant strains of H. influenzce type b have been isolated from children with meningitis5 and a chloramphenicol-resistant strain of H. influenzae type b causing meningitis has been reported.6 When antibiotic sensitivity tests have been done one of the two drugs can be withdrawn. Should strains of H. influenzx type b emerge which are resistant to both ampicillin and chloramphenicol, alternative drugs, such as co-trimoxazole will need to be considered. Although an aminoglycoside, especially gentamicin or tobramycin, could be useful in epiglottitis, the limited penetration of these drugs into cerebrospinal fluid would render them of doubtful value in meningitis.
I thank Dr Hugh Douglas and Dr Thomas Allen for their approval the case-notes of their patient, and Mr Andrew Moore for his
to use
technical assistance.
Microbiology Department, Adelaide Children’s Hospital, North Adelaide, South Australia 5006
well
as
children. Skilled
nasotra-
P., Utley, H. Mol. Pharmac. 1978, 4, 572. 3. Tisman, G., Wu, S. J. G. Proceedings of Second International Conference on Adjuvant Therapy of Cancer, 1979; abstr. 1. Blass, J. P., Gibson, G. E. New Engl. J. Med. 1977, 297, 1367.
DAVID HANSMAN
GLUCAGON AND INSULIN IN PANCREATIC EXOCRINE SECRETIONS
R. K. NADELLA
AMPICILLIN-INSENSITIVE HÆMOPHILUS INFLUENZÆ TYPE B CAUSING ACUTE EPIGLOTTITIS
which
cheal intubation’ and suitable chemotherapy are the keystones in management-intubation to relieve respiratory obstruction and chemotherapy to halt the bactersemia and so prevent infective complications, especially pneumonia, meningitis, and arthritis. In this hospital we have seen a child with epiglottitis in whom blood culture yielded an ampicillin-insensitive strain of H. influenzae type b. This was a girl aged 2 years and 11 months who presented on Oct. 27, 1978, with anorexia and fever of 1 day’s duration, followed by increasing respiratory distress. She was mildly febrile (37’4°C) and her epiglottis was reddened and swollen. A blood-sample for culture was collected, and the child was intubated and ampicillin administered intravenously at a dose of 200 mg/kg/day in four equally divided doses. There was a rapid improvement: within 24 h she was afebrile and could be extubated. Ampicillin was stopped after 48 h and replaced with amoxycillin orally in a dose of 50 mg/kg/day. H. influenzae type b was isolated from the blood culture; on disc diffusion testing2 the strain was insensitive to ampicillin (2 pLg) and tests for p-lactamaselyielded a positive result; the isolate was sensitive to chloramphenicol (10 ug), tetracycline (10 ug), trimethoprim (1.25 tg), and co-trimoxazole (25 tg). With the moderate inoculum of 1000 viable units the minimal inhibitory concentration (M.iC.) was 2.0 p.g ampicillin per ml, whereas an ampicillin-sensitive strain of H. influenzce type b tested as a control showed a mt.i.c. of 0.5 g per ml; tests were done by plate titration on heated blood
SIR,-Carr-Locke and Track’ found significant amounts of human pancreatic polypeptide (PP) in pancreatic juice obtained during cannulation of the papilla of Vater. Since others8 had noted that intravenous administration of PP 1.
Sweeney,
D.
B., Allen,
T.
H., Steven, I. M. Anœsth. intens. Care, 1973, 1,
526.
Hansman, D. Lancet, 1975, ii, 893. Perret, C. J. Nature, 1954, 174, 1012. Slack, M. P. E., Wheldon, D. B., Turk, D. C. Lancet, 1977, ii, 906. 5. Tomeh, M. O., Starr, S. E., McGowan, J. E., Terry, P. M., Nahmias, A J. J. Am. med. Ass. 1974, 229, 295. 6. Kinmonth, A. L., Storrs, C. N., Mitchell, R. G. Br. med. J. 1978, i, 694. 7. Carr-Locke, D. L., Track, N. S., Lancet, 1979, i, 151. 8. Greenberg, G. R., McCloy, R. F., Adrian, T. E., Chadwick, V. S., Baron, J. H., Bloom, S. R. ibid. 1978, ii, 1280.
2. 3. 4.