- Email: [email protected]
LUNG RESECTION FOR BRONCHIECTASIS
631
lative effect is shown over several days.Io
by the concentrations
in the
plasma
long-acting sulphonamide has some advantages in both prophylactic and therapeutic use. Only one dose a day is needed, and in the treatment of most susceptible infections an initial dose of 1-0 g. followed by 0-5 g. every twenty-four hours is sufficient.I2 When high sustained blood-levels are required to eliminate more resistant organisms, an initial dose of 2-0 g. followed by 1-0 g. daily may be given. In the prophylaxis of streptococcal infections a weekly dose of 30 mg. per kg. of body-weight has been used (about 1-5-2-0 g. in an adolescent or young adult), and has been found satisfactory in a preliminary trial. 13 As the drug so readily accumulates in the body it is advisable to determine the blood-level periodically if long courses are given, especially if renal function is impaired. The other compound, sulphachloropyridazine, shows numerous metabolic differences. After a single oral dose the chloro derivative has a half-life in the plasma about a fifth as long as that of the methoxy derivative. Urinary excretion is much more rapid with the chloro derivative, A
and the time taken for elimination of half the dose in the urine is only about a seventh of that for the methoxy compound.9As a result, higher and more frequent dosage -usually about 0-5-1-0 g. thrice daily-is needed with sulphachloropyridazine to attain adequate blood-levels. On the other hand, urinary levels are higher, and a smaller proportion is present in the conjugated form. This drug may therefore be useful in the treatment of urinary-tract infections 14 ; but in pyelonephritis high plasma and tissue concentrations may be more important than the level in the urine, which does not come into contact with the more deeply seated lesions. On this basis, sulphamethoxypyridazine has been used to produce high, sustained blood-levels for the treatment of urinary-tract infections, and satisfactory results have been obtained.I5 The investigations so far on these two sulphonamidopyridazine derivatives show that they are among the most active sulphonamides. They are clinically well tolerated. Their toxicity is probably similar to that of other antibacterial sulphonamides in current use, though this can be fully established only by longer clinical trials. These two compounds, so closely related chemically, have some sharply differing biological properties which will greatly influence their therapeutic applications. RESEARCH ON POPULATION GENETICS
THE Medical Research Council began to take an active part in developing research in genetics over twenty years ago. With the advent of nuclear energy this activity was increased, and the Council is seeking to recruit additional workers for research in university departments or as members of its own scientific staff.16The Council itself has lately made two important moves: first, the formation in London of a Clinical Genetics Research unit under the direction of Dr. J. A. Fraser Roberts, which began work last April; and now the establishment at Oxford of a complementary Population Genetics Research Unit under the direction of Dr. A. C. Stevenson, formerly professor of social and preventive medicine at the Queen’s University of Belfast. 13. Lepper, M. H., Simon, A. J., Marienfeld, C. J. Ann. N. Y. Acad. Sci. 1957, 69, 485. 14. Nanda, K. G. S., Batterman, R. C. ibid. p. 521. 15. Harris, A. P., Riley, H. D., Jr., Knight, V. Arch. intern. Med. 1957, 100, 701. 16. Report of the Medical Research Council for the Year 1955-56; p. 9. H.M. Stationery Office, 1957.
Hypotheses on the genetical structure of human populations are derived largely from theoretical considerations or from observations on experimental populations of animals; and the new unit will seek to test the validity of these in man. The unit’s work will probably include studies of the frequencies and patterns of marker traits in the population and of genetical linkage, and possibly studies of fertility patterns and of selection factors in marriages. The unit is to be accommodated at the Warneford Hospital and will in addition have offices in Oxford. If there is a local demand, genetical counselling clinics may be established
at
various
centres.
LUNG RESECTION FOR BRONCHIECTASIS
ago we drew attention to the favourable results of conservative management of bronchiectasis and suggested that surgical treatment is rarely desirable, because of the relatively high incidence even in experienced hands of postoperative complications such as pulmonary collapse, and because of the considerable risk A of further bronchiectasis in the remaining lung.! follow-up study by Gudbjerg2 of Copenhagen illustrates these points afresh. 52 patients treated by dissection lobectomy or segmental resection for unilateral disease were re-examined bronchographically after an average interval of five years. 2 patients had died in the immediate postoperative period, and 4 more during the follow-up; and in this potentially most favourable group only half were cured in the sense of having no remaining bronchiectasis demonstrable radiologically. (Nothing is said about pulmonary function in these patients.) In a third, fresh bronchiectasis was found to have developed, and the remainder had not had a radical operation. The results were better for rightsided operations, especially if confined to the middle lobe. Operations on the left lung were often unsatisfactory, particularly if the lingula was conserved after a lower lobectomy. As would be expected, postoperative pulmonary collapse or empyema increased the risk of a bad result, and so did increasing age. In a small group with unilateral disease submitted to pneumonectomy, the mortality was prohibitive, and half the patients died within four months. Of 32 patients with bilateral disease 5 died soon after operation and a further 8 during followup ; all but 2 survivors showed extension of the disease. By the criteria of the death-rate and radiological findings these results are discouraging; and knowledge of the functional capacity of those who were " cured " might make the picture still more sombre. There are probably several reasons. The incidence of postoperative complications was considerable, and the average age was very high; the series included people in their fifties and sixties who would not be operated on nowadays. It is true that antibiotics, physiotherapy, anxsthesia, and surgical technique have all improved since these patients had their operations, but improved technique is unlikely to affect the most important factor-namely, the inevitable distortion of the bronchial tree and interference with the drainage of the remaining bronchi. Gudbjerg suggests that there may be a further factor-constitutional susceptibility to bronchial infection.
A
YEAR or two
THE death has been announced of Sir THOMAS WILSON, consultant gynxcologist to Adelaide Hospital. 1. Lancet, 1955, ii, 489. 2. Gudbjerg, C. E. Acta
radiol., Stockh, 1957, suppl.
143.
lative effect is shown over several days.Io
by the concentrations
in the
plasma
long-acting sulphonamide has some advantages in both prophylactic and therapeutic use. Only one dose a day is needed, and in the treatment of most susceptible infections an initial dose of 1-0 g. followed by 0-5 g. every twenty-four hours is sufficient.I2 When high sustained blood-levels are required to eliminate more resistant organisms, an initial dose of 2-0 g. followed by 1-0 g. daily may be given. In the prophylaxis of streptococcal infections a weekly dose of 30 mg. per kg. of body-weight has been used (about 1-5-2-0 g. in an adolescent or young adult), and has been found satisfactory in a preliminary trial. 13 As the drug so readily accumulates in the body it is advisable to determine the blood-level periodically if long courses are given, especially if renal function is impaired. The other compound, sulphachloropyridazine, shows numerous metabolic differences. After a single oral dose the chloro derivative has a half-life in the plasma about a fifth as long as that of the methoxy derivative. Urinary excretion is much more rapid with the chloro derivative, A
and the time taken for elimination of half the dose in the urine is only about a seventh of that for the methoxy compound.9As a result, higher and more frequent dosage -usually about 0-5-1-0 g. thrice daily-is needed with sulphachloropyridazine to attain adequate blood-levels. On the other hand, urinary levels are higher, and a smaller proportion is present in the conjugated form. This drug may therefore be useful in the treatment of urinary-tract infections 14 ; but in pyelonephritis high plasma and tissue concentrations may be more important than the level in the urine, which does not come into contact with the more deeply seated lesions. On this basis, sulphamethoxypyridazine has been used to produce high, sustained blood-levels for the treatment of urinary-tract infections, and satisfactory results have been obtained.I5 The investigations so far on these two sulphonamidopyridazine derivatives show that they are among the most active sulphonamides. They are clinically well tolerated. Their toxicity is probably similar to that of other antibacterial sulphonamides in current use, though this can be fully established only by longer clinical trials. These two compounds, so closely related chemically, have some sharply differing biological properties which will greatly influence their therapeutic applications. RESEARCH ON POPULATION GENETICS
THE Medical Research Council began to take an active part in developing research in genetics over twenty years ago. With the advent of nuclear energy this activity was increased, and the Council is seeking to recruit additional workers for research in university departments or as members of its own scientific staff.16The Council itself has lately made two important moves: first, the formation in London of a Clinical Genetics Research unit under the direction of Dr. J. A. Fraser Roberts, which began work last April; and now the establishment at Oxford of a complementary Population Genetics Research Unit under the direction of Dr. A. C. Stevenson, formerly professor of social and preventive medicine at the Queen’s University of Belfast. 13. Lepper, M. H., Simon, A. J., Marienfeld, C. J. Ann. N. Y. Acad. Sci. 1957, 69, 485. 14. Nanda, K. G. S., Batterman, R. C. ibid. p. 521. 15. Harris, A. P., Riley, H. D., Jr., Knight, V. Arch. intern. Med. 1957, 100, 701. 16. Report of the Medical Research Council for the Year 1955-56; p. 9. H.M. Stationery Office, 1957.
Hypotheses on the genetical structure of human populations are derived largely from theoretical considerations or from observations on experimental populations of animals; and the new unit will seek to test the validity of these in man. The unit’s work will probably include studies of the frequencies and patterns of marker traits in the population and of genetical linkage, and possibly studies of fertility patterns and of selection factors in marriages. The unit is to be accommodated at the Warneford Hospital and will in addition have offices in Oxford. If there is a local demand, genetical counselling clinics may be established
at
various
centres.
LUNG RESECTION FOR BRONCHIECTASIS
ago we drew attention to the favourable results of conservative management of bronchiectasis and suggested that surgical treatment is rarely desirable, because of the relatively high incidence even in experienced hands of postoperative complications such as pulmonary collapse, and because of the considerable risk A of further bronchiectasis in the remaining lung.! follow-up study by Gudbjerg2 of Copenhagen illustrates these points afresh. 52 patients treated by dissection lobectomy or segmental resection for unilateral disease were re-examined bronchographically after an average interval of five years. 2 patients had died in the immediate postoperative period, and 4 more during the follow-up; and in this potentially most favourable group only half were cured in the sense of having no remaining bronchiectasis demonstrable radiologically. (Nothing is said about pulmonary function in these patients.) In a third, fresh bronchiectasis was found to have developed, and the remainder had not had a radical operation. The results were better for rightsided operations, especially if confined to the middle lobe. Operations on the left lung were often unsatisfactory, particularly if the lingula was conserved after a lower lobectomy. As would be expected, postoperative pulmonary collapse or empyema increased the risk of a bad result, and so did increasing age. In a small group with unilateral disease submitted to pneumonectomy, the mortality was prohibitive, and half the patients died within four months. Of 32 patients with bilateral disease 5 died soon after operation and a further 8 during followup ; all but 2 survivors showed extension of the disease. By the criteria of the death-rate and radiological findings these results are discouraging; and knowledge of the functional capacity of those who were " cured " might make the picture still more sombre. There are probably several reasons. The incidence of postoperative complications was considerable, and the average age was very high; the series included people in their fifties and sixties who would not be operated on nowadays. It is true that antibiotics, physiotherapy, anxsthesia, and surgical technique have all improved since these patients had their operations, but improved technique is unlikely to affect the most important factor-namely, the inevitable distortion of the bronchial tree and interference with the drainage of the remaining bronchi. Gudbjerg suggests that there may be a further factor-constitutional susceptibility to bronchial infection.
A
YEAR or two
THE death has been announced of Sir THOMAS WILSON, consultant gynxcologist to Adelaide Hospital. 1. Lancet, 1955, ii, 489. 2. Gudbjerg, C. E. Acta
radiol., Stockh, 1957, suppl.
143.