- Email: [email protected]
SALMON DISEASE
296
apparatus for detecting and reporting aircraft altitude already exists, so here is a practical way of ensuring that the standards are met. Technological progress, after all, has a momentum of its own, a momentum which can be guided or deflected but not entirely arrested. We shall do better to ride the supersonic whirlwind rather than defy it.
SPINAL NEUROFIBROMAS
WHEREAS more than 80 % of intracranial neoplasms eventually prove to be malignant, the converse is true of new growths within the spinal canal, where the great majority are benign. Early diagnosis of intraspinal tumours is imperative, since the earlier operation is performed the less likely is any significant residual disability. Gautier-Smith 1 has therefore done a useful service by analysing the clinical, radiological, and investigative features of 115 cases of spinal neurofibroma admitted to hospital under the care of Mr. Wylie
quite as good in those whose paraplegia was severe operation; nevertheless, of 18 patients with severe symptoms and signs 5 became quite normal and a further 9 had only very mild residual disability. The greatest diagnostic difficulty arose in patients with lumbosacral tumours; and in 1 the initial diagnosis was spinal subarachnoid haemorrhage. The average duration of symptoms before operation was forty-nine months, mainly because the great majority had been diagnosed as prolapse of the lumbar intervertebral disc. GautierSmith1 emphasises that the early manifestations of lumbosacral neurofibroma cannot be distinguished clinically from those of prolapsed disc. Sciatic pain was a common feature, and in two-thirds of patients straight X-rays failed to reveal any changes pointing to an intraspinal neoplasm. He maintains that there is a strong case for performing lumbar puncture and myelography in patients with sciatica whose symptoms have persisted for several months despite conservative management. Only in 3 of the lumbosacral patients was the c.s.F. protein less than 50 mg. per 100 ml. and in more than
were not
McKissock in the twenty years between 1945 and 1964. He has divided them into three groups, according to the site of the tumour-cervical, thoracic, and lumbosacral. In the 37 patients with cervical neurofibromas, pain was usually the first complaint (in 18), but symptoms of
spinal-cord dysfunction were nearly as common (16). Symptoms had been present for an average of twenty months before operation, and at the time of surgery all but 2 patients had signs of cord compression, 14 (38%) had sphincter disturbance and only 9 (24%) had been free from pain. All 6 patients who had had symptoms for more than four years had had root pains for some time before other symptoms began, and many of them had been regarded as having cervical spondylosis or prolapse of a cervical disc. The average age of the tumour cases, however, was 39-7 years, which is substantially lower than the average for patients with cervical myelopathy due to spondylosis: and 22 (59%) of the cervicalneurofibroma patients had diagnostic changes on plain X-ray films. Difficulty in distinguishing the condition from multiple sclerosis and intramedullary tumour was noted in the 9 patients who were free from pain and in 8 in whom the cerebrospinal-fluid protein was normal. In 18 (58%) of patients whose c.s.F. was examined the protein content was below 100 mg. per 100 ml. The results of operation in this group were good, and 32 (86-5%) of patients had virtually unrestricted activity within six months of the operation. Root pain was more common in the 44 patients with thoracic neurofibromas. Although cord compression occurred in 42 of the 44 patients and sphincter disturbance in 26 (59%) the relatively late appearance of these symptoms was somewhat unexpected in this group and may have explained why the average duration of symptoms before operation was twenty-seven months. Root pain had often been present for several years before signs of cord compression appeared. The plain X-rays showed pedicular erosion or other characteristic features in only about a third of cases ; but in all but 1 patient in this group the protein in the lumbar c.s.F. was more than 50 mg. per 100 ml., and in 11 patients the figure was greater than 1 g. per 100 ml. Surgical results were also good in this group, and 39 patients (89%) were able to work full-time after operation. The ultimate results 1.
Gautier-Smith,
P. C.
Brain, 1967, 90,
359.
before
half it was raised above 500 mg. per 100 ml. The crucial investigation is, of course, opaque myelography carried out by the lumbar route. Myelography invariably disclosed the neoplasm in the cervical and dorsal cases, and in only 2 patients was there any important side-effect (retention of urine, which recovered completely). The myelogram was also positive in the vast majority of patients with lumbosacral lesions, but in 1 the initial examination failed to reveal a tumour although a repeat myelogram three years later demonstrated it. The results of operation in the lumbosacral group were not so satisfactory as in the cervical and dorsal cases, in that only 22 out of 34 (65%) made a reasonably complete This difference can presumably be linked to the long delay in diagnosis in several patients and to the fact that the tumour was often so intimately connected with the roots of the cauda equina that total removal was impossible. Satisfactory treatment would almost certainly have been possible if these cases had been diagnosed earlier. Gautier-Smith concludes that although spinal neurofibromas may present in a variety of ways, root pain is a prominent feature in most cases. Had patients with pain of this kind been investigated earlier with plain X-rays, c.s.F. examination, and myelography, much illness would have been saved and the surgical results, good as they were, might have been improved.
recovery.
SALMON DISEASE
THOSE who have been puzzled by the many produring the past two years on the fatal disease of salmon seen first in Irish and later in English rivers may find some comforting parallels in the early history of human bacteriology. Much of this was a catalogue of attempts to link ill-defined diseases with microorganisms which were difficult to isolate and impossible to identify. Henle’s criteria of pathogenicity had been forgotten and Koch’s postulates not yet formulated. A contribution2 from two distinguished bacteriologists summarises what is known with certainty about this salmon disease. It is not much. Among anglers the three main causes of death in salmon are-apart from a legitimate end on a hookattacks by seals, furunculosis due to Aeromonas salmon-
nouncements
2.
Ajmal, M., Hobbs, B. C. Nature, Lond., 1967, 215,
141.
297 "
icida, and found dead" . The Irish disease was something different. It killed a large number of the fish in an affected river and no-one had seen the like of it. It was characterised by haemorrhagic or ulcerated patches on the skin, mostly on the upper surfaces of the body and often covered with a layer of fungal growth due to Saprolegna sp. Pseudomonas spp. and Aeromonas liquefaciens were found in many of these lesions, but these organisms are not uncommon on healthy fish of all sorts, and they probably play no part in causing salmon disease. The diseases of game animals have had more attention in the United States than here. The traditions of the frontier are not extinct, and the pursuit of mammals or fish is a major national interest in which a lot of money is involved. It was almost fifty years ago that Davis described a lethal disease of game fish associated with a bacterium which he could not grow in vitro but which, in suspension, arranged itself in a palisade of parallel organisms. Because of this habit he labelled it Bacillus columnaris. Later workers have devised a medium which will support its growth, but the systematists are still debating whether it belongs to the genus Chondrococcus or Cytophaga. This organism has been isolated from many of the diseased salmon during the recent outbreak and, later, from coarse fish in various parts of England. Ajmal and Hobbs2 give clear directions for its cultivation and recognition, and this should encourage a more exact definition of the disease. As a sideline to this inquiry, two other bacteria which seem to cause disease in fish have been identified.3 One is either a Corynebacterium or a Listeria, the other is allied to Pasteurella. A knowledge of the causal organism is obviously the first step towards some understanding of the pathology and epidemiology of this disease, but the difficulties are forbidding. The pioneers who studied anthrax could count both the dead and the survivors. Some animals reported dead of anthrax died of other causes, but they
could be distinguished without difficulty. Healthy and infected animals could be kept in a controlled environment. Materia morbis could be inoculated and the effects observed. The problems of the piscine pathologist are not so easy. Dead fish are likely to be carried away by stream or tide, and estimates of mortality must be guesswork. There is seldom a laboratory handy to a salmon river, and postmortem material in a state of moderate decay is not satisfactory. Technical difficulties make experimental work on salmon almost impossible, but the discovery that the disease may attack perch and dace offers some hope. The first need is
find out how the disease may be fish and how it spreads in Nature. Will the infection pass through the intact skin or is previous traumatic damage necessary? Physical contact cannot be excluded as a means of infection, as anyone knows who has watched the shoals of salmon under the bridge at Galway. That the disease first appeared almost simultaneously in several adjacent rivers in Co. Kerry suggested that the infection had begun when the fish were still at sea. Salmon return to the river where they were spawned-but not invariably and a few eccentrics seem to try one or more other rivers before they begin their ascent. Did some of these carry the disease from river to river? The almost simultaneous appearance of
passed from fish
3.
to
to
Ajmal, M., Hobbs, B. C. ibid. p. 142.
the disease among coarse fish in rivers so far apart as the Trent and the Parrett is more difficult to explain. A few salmon try to make their way up both these unprofitable rivers, and it is known that birds such as a mallard can carry weed and aquatic snails from river to river; but such guesses do not hold much promise. The epidemiology of the disease, so far as we know it, almost suggests that a spread from fish to fish may be only a secondary factor in its distribution. In the United States this disease was associated with especially hot weather: this does not hold good here, but a search for some environmental cause is overdue. The specialised methods needed to isolate C. columnaris have been applied to few fish without evidence of this disease. Perhaps it is a not uncommon
organism.
CHOICE OF ANTIBIOTIC
RECENT leading articles on chloramphenicol 1have been followed by further correspondence on the use of this controversial drug. Its efficacy as a broad-spectrum antibiotic is unchallenged, but there is considerable disagreement on its indications and toxicity. While the Food and Drug Administration in the U.S.A. and the Committee on Safety of Drugs in the United Kingdom have warned of its serious effects on the bone-marrow, it continues to be widely used abroad. Last year, in a symposium on the chemotherapy of infections with special emphasis on chloramphenicol,3 Italian workers in particular spoke of its value in a wide variety of circumstances, and claimed that bone-marrow depression was not a significant hazard in their experience. Similarly, Sheba4 has described its wide use in Israel with an apparent lack of serious blood dyscrasias. He suggests that differences in formulation or dose may be responsible for regional differences in toxicity, or that genetic and racial factors may be important. These questions are at present unresolved. We do realise, however, as Freston has emphasised,5 that chloramphenicol probably gives rise to two forms of bone-marrow toxicity. One is an acute effect which is found commonly at blood-levels above 25 ;jLg. per 100 ml. The white-blood-cell count falls, and the platelet and red-cell count may also be depressed. Vacuolisation and inhibition of cellular respiration occur. These changes are readily and rapidly reversed when the drug is discontinued. Secondly chloramphenicol may give rise to aplastic anaemia, which is usually, if not always, fatal; and it may become manifest several weeks after discontinuation of the drug. While we would repeat that chloramphenicol should not be withheld because of possible toxicity when the clinical indications for its use are unequivocal and there is no suitable alternative, it must be restricted to such cases. Its prescription for upperrespiratory-tract infections, particularly when no bacteriological studies have been carried out, can hardly be defended. One attraction of chloramphenicol is its effectiveness over a wide spectrum of bacterial activity, with only a relatively small proportion of resistant strains. This has often made it the drug of choice where the severity of an 1. Lancet, 1967, i, 32. 2. Br. med. J. 1967, i, 649. 3. Postgrad. med. J. 1967, 43. Supplement: The Chemotherapy of Infections. 4. Sheba, C. Lancet, 1967, i, 1007. 5. Freston, J. Postgrad. med. J. 1967, 43. Supplement: The Chemotherapy of Infections.
apparatus for detecting and reporting aircraft altitude already exists, so here is a practical way of ensuring that the standards are met. Technological progress, after all, has a momentum of its own, a momentum which can be guided or deflected but not entirely arrested. We shall do better to ride the supersonic whirlwind rather than defy it.
SPINAL NEUROFIBROMAS
WHEREAS more than 80 % of intracranial neoplasms eventually prove to be malignant, the converse is true of new growths within the spinal canal, where the great majority are benign. Early diagnosis of intraspinal tumours is imperative, since the earlier operation is performed the less likely is any significant residual disability. Gautier-Smith 1 has therefore done a useful service by analysing the clinical, radiological, and investigative features of 115 cases of spinal neurofibroma admitted to hospital under the care of Mr. Wylie
quite as good in those whose paraplegia was severe operation; nevertheless, of 18 patients with severe symptoms and signs 5 became quite normal and a further 9 had only very mild residual disability. The greatest diagnostic difficulty arose in patients with lumbosacral tumours; and in 1 the initial diagnosis was spinal subarachnoid haemorrhage. The average duration of symptoms before operation was forty-nine months, mainly because the great majority had been diagnosed as prolapse of the lumbar intervertebral disc. GautierSmith1 emphasises that the early manifestations of lumbosacral neurofibroma cannot be distinguished clinically from those of prolapsed disc. Sciatic pain was a common feature, and in two-thirds of patients straight X-rays failed to reveal any changes pointing to an intraspinal neoplasm. He maintains that there is a strong case for performing lumbar puncture and myelography in patients with sciatica whose symptoms have persisted for several months despite conservative management. Only in 3 of the lumbosacral patients was the c.s.F. protein less than 50 mg. per 100 ml. and in more than
were not
McKissock in the twenty years between 1945 and 1964. He has divided them into three groups, according to the site of the tumour-cervical, thoracic, and lumbosacral. In the 37 patients with cervical neurofibromas, pain was usually the first complaint (in 18), but symptoms of
spinal-cord dysfunction were nearly as common (16). Symptoms had been present for an average of twenty months before operation, and at the time of surgery all but 2 patients had signs of cord compression, 14 (38%) had sphincter disturbance and only 9 (24%) had been free from pain. All 6 patients who had had symptoms for more than four years had had root pains for some time before other symptoms began, and many of them had been regarded as having cervical spondylosis or prolapse of a cervical disc. The average age of the tumour cases, however, was 39-7 years, which is substantially lower than the average for patients with cervical myelopathy due to spondylosis: and 22 (59%) of the cervicalneurofibroma patients had diagnostic changes on plain X-ray films. Difficulty in distinguishing the condition from multiple sclerosis and intramedullary tumour was noted in the 9 patients who were free from pain and in 8 in whom the cerebrospinal-fluid protein was normal. In 18 (58%) of patients whose c.s.F. was examined the protein content was below 100 mg. per 100 ml. The results of operation in this group were good, and 32 (86-5%) of patients had virtually unrestricted activity within six months of the operation. Root pain was more common in the 44 patients with thoracic neurofibromas. Although cord compression occurred in 42 of the 44 patients and sphincter disturbance in 26 (59%) the relatively late appearance of these symptoms was somewhat unexpected in this group and may have explained why the average duration of symptoms before operation was twenty-seven months. Root pain had often been present for several years before signs of cord compression appeared. The plain X-rays showed pedicular erosion or other characteristic features in only about a third of cases ; but in all but 1 patient in this group the protein in the lumbar c.s.F. was more than 50 mg. per 100 ml., and in 11 patients the figure was greater than 1 g. per 100 ml. Surgical results were also good in this group, and 39 patients (89%) were able to work full-time after operation. The ultimate results 1.
Gautier-Smith,
P. C.
Brain, 1967, 90,
359.
before
half it was raised above 500 mg. per 100 ml. The crucial investigation is, of course, opaque myelography carried out by the lumbar route. Myelography invariably disclosed the neoplasm in the cervical and dorsal cases, and in only 2 patients was there any important side-effect (retention of urine, which recovered completely). The myelogram was also positive in the vast majority of patients with lumbosacral lesions, but in 1 the initial examination failed to reveal a tumour although a repeat myelogram three years later demonstrated it. The results of operation in the lumbosacral group were not so satisfactory as in the cervical and dorsal cases, in that only 22 out of 34 (65%) made a reasonably complete This difference can presumably be linked to the long delay in diagnosis in several patients and to the fact that the tumour was often so intimately connected with the roots of the cauda equina that total removal was impossible. Satisfactory treatment would almost certainly have been possible if these cases had been diagnosed earlier. Gautier-Smith concludes that although spinal neurofibromas may present in a variety of ways, root pain is a prominent feature in most cases. Had patients with pain of this kind been investigated earlier with plain X-rays, c.s.F. examination, and myelography, much illness would have been saved and the surgical results, good as they were, might have been improved.
recovery.
SALMON DISEASE
THOSE who have been puzzled by the many produring the past two years on the fatal disease of salmon seen first in Irish and later in English rivers may find some comforting parallels in the early history of human bacteriology. Much of this was a catalogue of attempts to link ill-defined diseases with microorganisms which were difficult to isolate and impossible to identify. Henle’s criteria of pathogenicity had been forgotten and Koch’s postulates not yet formulated. A contribution2 from two distinguished bacteriologists summarises what is known with certainty about this salmon disease. It is not much. Among anglers the three main causes of death in salmon are-apart from a legitimate end on a hookattacks by seals, furunculosis due to Aeromonas salmon-
nouncements
2.
Ajmal, M., Hobbs, B. C. Nature, Lond., 1967, 215,
141.
297 "
icida, and found dead" . The Irish disease was something different. It killed a large number of the fish in an affected river and no-one had seen the like of it. It was characterised by haemorrhagic or ulcerated patches on the skin, mostly on the upper surfaces of the body and often covered with a layer of fungal growth due to Saprolegna sp. Pseudomonas spp. and Aeromonas liquefaciens were found in many of these lesions, but these organisms are not uncommon on healthy fish of all sorts, and they probably play no part in causing salmon disease. The diseases of game animals have had more attention in the United States than here. The traditions of the frontier are not extinct, and the pursuit of mammals or fish is a major national interest in which a lot of money is involved. It was almost fifty years ago that Davis described a lethal disease of game fish associated with a bacterium which he could not grow in vitro but which, in suspension, arranged itself in a palisade of parallel organisms. Because of this habit he labelled it Bacillus columnaris. Later workers have devised a medium which will support its growth, but the systematists are still debating whether it belongs to the genus Chondrococcus or Cytophaga. This organism has been isolated from many of the diseased salmon during the recent outbreak and, later, from coarse fish in various parts of England. Ajmal and Hobbs2 give clear directions for its cultivation and recognition, and this should encourage a more exact definition of the disease. As a sideline to this inquiry, two other bacteria which seem to cause disease in fish have been identified.3 One is either a Corynebacterium or a Listeria, the other is allied to Pasteurella. A knowledge of the causal organism is obviously the first step towards some understanding of the pathology and epidemiology of this disease, but the difficulties are forbidding. The pioneers who studied anthrax could count both the dead and the survivors. Some animals reported dead of anthrax died of other causes, but they
could be distinguished without difficulty. Healthy and infected animals could be kept in a controlled environment. Materia morbis could be inoculated and the effects observed. The problems of the piscine pathologist are not so easy. Dead fish are likely to be carried away by stream or tide, and estimates of mortality must be guesswork. There is seldom a laboratory handy to a salmon river, and postmortem material in a state of moderate decay is not satisfactory. Technical difficulties make experimental work on salmon almost impossible, but the discovery that the disease may attack perch and dace offers some hope. The first need is
find out how the disease may be fish and how it spreads in Nature. Will the infection pass through the intact skin or is previous traumatic damage necessary? Physical contact cannot be excluded as a means of infection, as anyone knows who has watched the shoals of salmon under the bridge at Galway. That the disease first appeared almost simultaneously in several adjacent rivers in Co. Kerry suggested that the infection had begun when the fish were still at sea. Salmon return to the river where they were spawned-but not invariably and a few eccentrics seem to try one or more other rivers before they begin their ascent. Did some of these carry the disease from river to river? The almost simultaneous appearance of
passed from fish
3.
to
to
Ajmal, M., Hobbs, B. C. ibid. p. 142.
the disease among coarse fish in rivers so far apart as the Trent and the Parrett is more difficult to explain. A few salmon try to make their way up both these unprofitable rivers, and it is known that birds such as a mallard can carry weed and aquatic snails from river to river; but such guesses do not hold much promise. The epidemiology of the disease, so far as we know it, almost suggests that a spread from fish to fish may be only a secondary factor in its distribution. In the United States this disease was associated with especially hot weather: this does not hold good here, but a search for some environmental cause is overdue. The specialised methods needed to isolate C. columnaris have been applied to few fish without evidence of this disease. Perhaps it is a not uncommon
organism.
CHOICE OF ANTIBIOTIC
RECENT leading articles on chloramphenicol 1have been followed by further correspondence on the use of this controversial drug. Its efficacy as a broad-spectrum antibiotic is unchallenged, but there is considerable disagreement on its indications and toxicity. While the Food and Drug Administration in the U.S.A. and the Committee on Safety of Drugs in the United Kingdom have warned of its serious effects on the bone-marrow, it continues to be widely used abroad. Last year, in a symposium on the chemotherapy of infections with special emphasis on chloramphenicol,3 Italian workers in particular spoke of its value in a wide variety of circumstances, and claimed that bone-marrow depression was not a significant hazard in their experience. Similarly, Sheba4 has described its wide use in Israel with an apparent lack of serious blood dyscrasias. He suggests that differences in formulation or dose may be responsible for regional differences in toxicity, or that genetic and racial factors may be important. These questions are at present unresolved. We do realise, however, as Freston has emphasised,5 that chloramphenicol probably gives rise to two forms of bone-marrow toxicity. One is an acute effect which is found commonly at blood-levels above 25 ;jLg. per 100 ml. The white-blood-cell count falls, and the platelet and red-cell count may also be depressed. Vacuolisation and inhibition of cellular respiration occur. These changes are readily and rapidly reversed when the drug is discontinued. Secondly chloramphenicol may give rise to aplastic anaemia, which is usually, if not always, fatal; and it may become manifest several weeks after discontinuation of the drug. While we would repeat that chloramphenicol should not be withheld because of possible toxicity when the clinical indications for its use are unequivocal and there is no suitable alternative, it must be restricted to such cases. Its prescription for upperrespiratory-tract infections, particularly when no bacteriological studies have been carried out, can hardly be defended. One attraction of chloramphenicol is its effectiveness over a wide spectrum of bacterial activity, with only a relatively small proportion of resistant strains. This has often made it the drug of choice where the severity of an 1. Lancet, 1967, i, 32. 2. Br. med. J. 1967, i, 649. 3. Postgrad. med. J. 1967, 43. Supplement: The Chemotherapy of Infections. 4. Sheba, C. Lancet, 1967, i, 1007. 5. Freston, J. Postgrad. med. J. 1967, 43. Supplement: The Chemotherapy of Infections.