872
experience are considered, rational choices then can be made for each patient. With either corticosteroid regimen, other measures need to be maintained to keep down the dosage. The withdrawal of chronic bronchodilator therapy from patients who had attained improved control with the addition of beclomethasone resulted in increased symptoms in one study." It is also important to emphasise that the use of non-corticosteroid measures, including chronic theophylline therapy in doses that maintain serum-theophylline concentrations in the therapeutic range, 19,20 can avoid the continuous use of corticosteroids in most patients.21 Pediatric Allergy and Pulmonary Division Clinical Research Center, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, U.S.A.
pleural adriamycin, the flow had diminished to less than 50 ml (the tube was checked to ensure that it had not been blocked . No patient in the series so far has had systemic or topical toxicity, probably because of the small dose used. It can often be difficult to distinguish radiologically pleural fibrosis (induced by chemotherapy or by the disease) from pleural effusions even on decubitus views. We are now using ultrasound in an attempt to make this distinction. Medical Diagnostic Unit and Cancer Clinic, Henderson General Hospital, McMaster University, Hamilton, Ontario L8V
1C3, Canada
S. D. DESAI A. FIGUEREDO
MILES WEINBERGER BARRY SHERMAN
GASTRIC EMPTYING, FIBRE, AND ABSORPTION
SiR,—Dr Holt and his colleagues (March 24, p. 636) have
demonstrated
how the addition of dietary fibre in a glucosetheir gastrectomy patient converted a diabetic blood-sugar curve, by the internationally agreed criteria, to normal. At the same time the area under the 2 h curve fell by 23%, suggesting modification of events in the small intestine. The combination of 16 g guar and 10 g pectin made up in 400 ml will form a gel that is likely to delay gastric emptying, as Holt et al. have demonstrated. However, mixing two forms of fibre makes it difficult to determine the contribution of each to the effects on absorption and to the adverse effects experienced. When given with paracetamol the fibre flattened the plasma-paracetamol curve, reducing the area under the 8 h curve by 16%. Again there was a continuing, delayed absorption, long after gastric emptying, evidenced by the gentler decay slope and also the similar 24 h urinary recovery-rates. In the glucose-tolerance studies the addition of pectin flattened the blood-glucose curve but left the mean peak rise at 30 min, as in the control. Propantheline delayed the peak to 1 h and did not cause the gentle decay phase shown with fibre. These data would suggest that there is certainly a second mechanism involved in the modification of absorption by fibre. The effect on gastric emptying is obviously important but further work is required to explain the mechanism of modification of absorption in the small bowel. tolerance
INTRACAVITARY DOXORUBICIN IN MALIGNANT EFFUSIONS
SIR,-We read with interest the letter by Dr Tattersall and colleagues (Feb. 17, p. 390). We are doing a controlled trial
comparing intrapleural doxorubicin (administered through an intercostal tube) with drainage via intercostal tube but without addition of any topical chemotherapeutic agent. Whilst it is too soon to make any firm statements (only fourteen patients so far, with short follow-ups) our early experience suggests that caution is needed in the interpretation of the absolute value of topical doxorubicin or other chemotherapeutic agents. Two out of three patients in our series who have had no intrapleural doxorubicin (intercostal tube only) have done very well; they have not had recurrent effusions over the past 20 and 28 weeks. The remaining patient who died 3 days after institution of intracostal drainage, had less than 100 ml of fluid at necropsy but the pleura were much thickened and affected by adhesions. These satisfactory results (in terms of recurrence of effusion) might have been ascribed to the chemotherapeutic agent had one been given. We were concerned about the possible local and systemic complications of doxorubicin and so we used small doses (5 mg in 15 ml normal saline). However, after the first six patients, we increased the dose to 10 mg in 15 ml saline, and this dose has been used in the controlled,trial. Of ten patients with 10 mg doxorubicin (’Adriamycin’) administered intrapleurally, three survived less than four weeks and one was lost to follow-up after the procedure so no firm conclusions can be drawn about possible recurrences on these four patients. One patient had no recurrence during 1-year survival. Another patient had no recurrence during a 6-month survival period. A third patient survived for 27 weeks without further tapping of the pleural effusion being necessary. Two patients have had no recurrence 10 weeks and 9 weeks after the intrapleural doxorubicin and are still alive. Although one patient survived 10 weeks, he required two further pleural taps and, at necropsy, had 2 litres of fluid with very adherent pleura. In two patients (one surviving less than 4 weeks), the response to intra-pleural adriamycin was dramatic: before intrapleural adriamycin 1-1/2 litres of fluid was draining through the pleural tube every 24 h, but within 24 h of intra16.
Yernault, J-C., Leclercq, R., Schandevyl, W., Virasoso, E., De Coster, A.,
Copinschi, G. Chest, 1977, 71, 698. 17. Toogood, J. H., Lefcoe, N. M., Haines, D. S. M., Jennings, B., Errington, N., Baksh, L., Chuang, L. J. Allergy clin. Immun. 1977, 59, 298. 18.
Richards, W., Platzker, A., Church, J. A., Yamamoto, F., Foster, S. Ann.
Allergy, 1978, 41, 274. 19. Hendeles, L., Weinberger, M., Wyatt, R. Am. J. Dis. Child. 1978, 132, 876. 20. Weinberger, M., Hendeles, L, Bighley, L. New Engl J. Med. 1978, 299, 852. 21. Ekwo, E., Weinberger, M. J. Allergy clin. Immun. 1978, 61, 240
test on
Department of Gastroenterology, Central Middlesex Hospital, London NW10
RODNEY H. TAYLOR
SIR,-Dr Holt and his colleagues have shown that guar gum and pectin significantly delay the gastric emptying of chelate of indium-113 in man and that the relation between the area under the plasma-paracetamol time curve and % test solution emptied from the stomach in 30 min was not significantly different when control and gel-fibre studies were compared. This implied that the altered gastric emptying was sufficient to explain the change of paracetamol absorption-rate. However, the results presented were such that, despite the significant positive correlation, only 34(’f (r2=0.34) of the variance of the area under the plasma-paracetamol/time curve could be attributed to changes of gastric emptying in the control studies. In the gel-fibre studies r2 was 0-42. Could other factors have been more important determinants of the area under the curve? Although gastric emptying is a major determinant of absorption-rate for orally administered substances does the same apply after high-viscosity meals? Is it possible that, in studies on high-viscosity meals, while gastric emptying and "absorpseem to be associated, both are dependent to other factors such as meal or lumen-content viscosity, rather than "absorption" rate being entirely dependent on gastric emptying? In other words a high-viscosity meal might slow gastric emptying but this may not account for ail of the slowing of absorption-rate. There might be some slowing of absorption-rate within the small gut. Would a proportion of
tion"
rates
may
some extent on
873 the variance of "absorption" rate much higher than 34-42% need to be due to gastric emptying before one could be certain that "the principal mode of action of gel-fibre on the absorption of glucose and paracetamol in man is a delay in the rate
of gastric emptying. In
a
1978,’
study reported I demonstrated
the Nutrition Society in December, that, in rats, when fractional gastric
to
emptying-rates and fractional disappearance-rates of glucose from the small intestine were measured 30 min and 1 h after low, intermediate, and high viscosity tube fed meals containing purified or depolymerised guar gum, fractional disappearancerates correlated well with gastric emptying-rates after all three meals (r=0.86, 0-99, at 1 h and 0.96, 0.90, 0.99 at 30 min for low, intermediate, and high viscosity meals, respectively; n=8 in each group). An analysis of variance, with the ratio of dependent significantly affect the value of the ratio. However, the high compared with the low viscosity meal prolonged the half-time of gastric emptying to 41 min from 16 min (P
experience are considered, rational choices then can be made for each patient. With either corticosteroid regimen, other measures need to be maintained to keep down the dosage. The withdrawal of chronic bronchodilator therapy from patients who had attained improved control with the addition of beclomethasone resulted in increased symptoms in one study." It is also important to emphasise that the use of non-corticosteroid measures, including chronic theophylline therapy in doses that maintain serum-theophylline concentrations in the therapeutic range, 19,20 can avoid the continuous use of corticosteroids in most patients.21 Pediatric Allergy and Pulmonary Division Clinical Research Center, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, U.S.A.
pleural adriamycin, the flow had diminished to less than 50 ml (the tube was checked to ensure that it had not been blocked . No patient in the series so far has had systemic or topical toxicity, probably because of the small dose used. It can often be difficult to distinguish radiologically pleural fibrosis (induced by chemotherapy or by the disease) from pleural effusions even on decubitus views. We are now using ultrasound in an attempt to make this distinction. Medical Diagnostic Unit and Cancer Clinic, Henderson General Hospital, McMaster University, Hamilton, Ontario L8V
1C3, Canada
S. D. DESAI A. FIGUEREDO
MILES WEINBERGER BARRY SHERMAN
GASTRIC EMPTYING, FIBRE, AND ABSORPTION
SiR,—Dr Holt and his colleagues (March 24, p. 636) have
demonstrated
how the addition of dietary fibre in a glucosetheir gastrectomy patient converted a diabetic blood-sugar curve, by the internationally agreed criteria, to normal. At the same time the area under the 2 h curve fell by 23%, suggesting modification of events in the small intestine. The combination of 16 g guar and 10 g pectin made up in 400 ml will form a gel that is likely to delay gastric emptying, as Holt et al. have demonstrated. However, mixing two forms of fibre makes it difficult to determine the contribution of each to the effects on absorption and to the adverse effects experienced. When given with paracetamol the fibre flattened the plasma-paracetamol curve, reducing the area under the 8 h curve by 16%. Again there was a continuing, delayed absorption, long after gastric emptying, evidenced by the gentler decay slope and also the similar 24 h urinary recovery-rates. In the glucose-tolerance studies the addition of pectin flattened the blood-glucose curve but left the mean peak rise at 30 min, as in the control. Propantheline delayed the peak to 1 h and did not cause the gentle decay phase shown with fibre. These data would suggest that there is certainly a second mechanism involved in the modification of absorption by fibre. The effect on gastric emptying is obviously important but further work is required to explain the mechanism of modification of absorption in the small bowel. tolerance
INTRACAVITARY DOXORUBICIN IN MALIGNANT EFFUSIONS
SIR,-We read with interest the letter by Dr Tattersall and colleagues (Feb. 17, p. 390). We are doing a controlled trial
comparing intrapleural doxorubicin (administered through an intercostal tube) with drainage via intercostal tube but without addition of any topical chemotherapeutic agent. Whilst it is too soon to make any firm statements (only fourteen patients so far, with short follow-ups) our early experience suggests that caution is needed in the interpretation of the absolute value of topical doxorubicin or other chemotherapeutic agents. Two out of three patients in our series who have had no intrapleural doxorubicin (intercostal tube only) have done very well; they have not had recurrent effusions over the past 20 and 28 weeks. The remaining patient who died 3 days after institution of intracostal drainage, had less than 100 ml of fluid at necropsy but the pleura were much thickened and affected by adhesions. These satisfactory results (in terms of recurrence of effusion) might have been ascribed to the chemotherapeutic agent had one been given. We were concerned about the possible local and systemic complications of doxorubicin and so we used small doses (5 mg in 15 ml normal saline). However, after the first six patients, we increased the dose to 10 mg in 15 ml saline, and this dose has been used in the controlled,trial. Of ten patients with 10 mg doxorubicin (’Adriamycin’) administered intrapleurally, three survived less than four weeks and one was lost to follow-up after the procedure so no firm conclusions can be drawn about possible recurrences on these four patients. One patient had no recurrence during 1-year survival. Another patient had no recurrence during a 6-month survival period. A third patient survived for 27 weeks without further tapping of the pleural effusion being necessary. Two patients have had no recurrence 10 weeks and 9 weeks after the intrapleural doxorubicin and are still alive. Although one patient survived 10 weeks, he required two further pleural taps and, at necropsy, had 2 litres of fluid with very adherent pleura. In two patients (one surviving less than 4 weeks), the response to intra-pleural adriamycin was dramatic: before intrapleural adriamycin 1-1/2 litres of fluid was draining through the pleural tube every 24 h, but within 24 h of intra16.
Yernault, J-C., Leclercq, R., Schandevyl, W., Virasoso, E., De Coster, A.,
Copinschi, G. Chest, 1977, 71, 698. 17. Toogood, J. H., Lefcoe, N. M., Haines, D. S. M., Jennings, B., Errington, N., Baksh, L., Chuang, L. J. Allergy clin. Immun. 1977, 59, 298. 18.
Richards, W., Platzker, A., Church, J. A., Yamamoto, F., Foster, S. Ann.
Allergy, 1978, 41, 274. 19. Hendeles, L., Weinberger, M., Wyatt, R. Am. J. Dis. Child. 1978, 132, 876. 20. Weinberger, M., Hendeles, L, Bighley, L. New Engl J. Med. 1978, 299, 852. 21. Ekwo, E., Weinberger, M. J. Allergy clin. Immun. 1978, 61, 240
test on
Department of Gastroenterology, Central Middlesex Hospital, London NW10
RODNEY H. TAYLOR
SIR,-Dr Holt and his colleagues have shown that guar gum and pectin significantly delay the gastric emptying of chelate of indium-113 in man and that the relation between the area under the plasma-paracetamol time curve and % test solution emptied from the stomach in 30 min was not significantly different when control and gel-fibre studies were compared. This implied that the altered gastric emptying was sufficient to explain the change of paracetamol absorption-rate. However, the results presented were such that, despite the significant positive correlation, only 34(’f (r2=0.34) of the variance of the area under the plasma-paracetamol/time curve could be attributed to changes of gastric emptying in the control studies. In the gel-fibre studies r2 was 0-42. Could other factors have been more important determinants of the area under the curve? Although gastric emptying is a major determinant of absorption-rate for orally administered substances does the same apply after high-viscosity meals? Is it possible that, in studies on high-viscosity meals, while gastric emptying and "absorpseem to be associated, both are dependent to other factors such as meal or lumen-content viscosity, rather than "absorption" rate being entirely dependent on gastric emptying? In other words a high-viscosity meal might slow gastric emptying but this may not account for ail of the slowing of absorption-rate. There might be some slowing of absorption-rate within the small gut. Would a proportion of
tion"
rates
may
some extent on
873 the variance of "absorption" rate much higher than 34-42% need to be due to gastric emptying before one could be certain that "the principal mode of action of gel-fibre on the absorption of glucose and paracetamol in man is a delay in the rate
of gastric emptying. In
a
1978,’
study reported I demonstrated
the Nutrition Society in December, that, in rats, when fractional gastric
to
emptying-rates and fractional disappearance-rates of glucose from the small intestine were measured 30 min and 1 h after low, intermediate, and high viscosity tube fed meals containing purified or depolymerised guar gum, fractional disappearancerates correlated well with gastric emptying-rates after all three meals (r=0.86, 0-99, at 1 h and 0.96, 0.90, 0.99 at 30 min for low, intermediate, and high viscosity meals, respectively; n=8 in each group). An analysis of variance, with the ratio of dependent significantly affect the value of the ratio. However, the high compared with the low viscosity meal prolonged the half-time of gastric emptying to 41 min from 16 min (P
