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COMPUTERISED TOMOGRAPHY AND SUBDURAL HÆMATOMAS
110 died before sensitivites showed these to be resistant to this therapy. A necropsy was not done. This is the first report of a scotochromogen (Runyon type it) infection complicating hairy-cell leukaemia. The four previously reported cases of atypical mycobacteriosis in this disease involved type i and type ni organisms.1-3 From these, Weinstein and colleagues concluded there may be a disproportionate risk of such infections becoming disseminated and proving fatal. There is great pressure to identify the responsible organism in this clinical setting, however, and this may have biased the selection of these cases for publication. Disseminated infection, which is generally defined by multi-organ involvement,4 was not established in our case, nor was it documented in one of the cases reported by Weinstein et al. Regional lymph-nodes were, however, involved in both instances.
Malignancy in general is associated with an increased prevalence of mycobacterial infection, and this can be attributed to impaired cellular immunity. This impairment is especially evident among the lymphoproliferative disorders, and is often compounded by cancer chemotherapy. With hairy-cell leukxmia, defective monocyte function and monocytopenia may be further relevant factors, as Weinstein et al. remarked. Most studies linking malignancy with mycobacteriosis have excluded infections with atypical organisms. Their relative importance was consequently unclear until the study of Feld and colleagues5 showed that atypical organisms were involved in 51% (30/59) of such cases. If these findings are corroborated, the possibility of an atypical, and hence drug-resistant, organism should be considered from the outset whenever acid-fast bacilli are found in such immunocompromised patients. This is well illustrated by our case, the patient dying shortly before drug insensitivity was confirmed. Divisions of Hematology/Oncology and Pulmonary Diseases,
Department of Medicine, Medical Center, University Hospital, Morgantown, West Virginia 26506,
U.S.A.
ALEX M. HENDRICK D. J. HENDRICK
CYCLOSPORIN A
SIR,-In
interesting pilot studies of the clinical use of published in your Dec. 23/30 issue, worrying
two
A side-effects were encountered which had not been seen in earlier animal experiments. As both groups of workers suggest, it is to be hoped that lower dosages of the drug will prove effectively immunosuppressant without interfering with hepatic and renal function. This problem can only be resolved when more is known about the uptake, distribution, and half-life of cyclosporin A in man, particularly when administered by mouth. Meantime, it may be worth trying to draw some tentative conclusions from the limited data available. Firstly, hepatic and renal disturbance of varying intensity has been encountered in most patients to whom the drug has been given, whether or not they have received allografts. The hepatic effects appear to be mild but directly related to cyclosporin-A administration and to dosage. Serum bilirubin, alkaline phosphatase, and alanine aminotransferase values are significantly raised but decline rapidly with reducing drug dosage and may even fall to normal within 24 h of abrupt drug withdrawal. Similarly, some renal disturbance has been observed in patients who previously had normal function; dysfunction appears to be dose related and rapidly reversible on withdrawal of cyclosporin A even in kidney-allografted patients
cyclosporin
2. Manes, J. L., Blair, O. M. J. Am. med. Ass. 1976, 236, 878. 3. Case Records of the Massachusetts General Hospital New Engl. J. Med. 1977, 296, 1218. 4. Caplan, M. H., Armstrong, D., Rosen, P., Cancer, 1974, 33, 850. 5. Feld, R., Bodey, G. P., Groschel, D. Archs intern. Med. 1976, 136, 67.
who have been anuric for several days. This, coupled with the surprisingly normal morphology demonstrated by the Cambridge group in biopsy material from non-functioning grafts, strongly suggests that cyclosporin A directly affects tubular cells without causing necrosis, and that dysfunction is unlikely to be caused by rejection or vascular defects. It is tempting to speculate that cyclosporin A is acting rather like a continuous overdose of antidiuretic hormone (A.D.H.). It is -after all a cyclic polypeptide which bears an admittedly superficial resemblance to A.D.H. This might promote conversion of A.T.P. to cyclic 3’,5’-A.M.P. and thence affect water permeability in the distal convolutions and collecting tubules. Perhaps selective binding to neurophysin-like proteins in the kidneys is a necessary precursor to this hormone-like activity. If this is the case, then it might be possible to counter the effect with other agents such as low dosages of corticosteroids and thus balance water permeability in the distal tubules. Division of Comparative Medicine, Clinical Research Centre, Harrow, Middlesex HA1 3UJ
C.
J. GREEN
COMPUTERISED TOMOGRAPHY AND SUBDURAL HÆMATOMAS on the prevention of secondary brain after head damage injury’ cites a paper by Galbraith et al. as evidence that computerised tomographic (c.T.) scanning is a reliable means of detecting subdural hxmatomas. While this is true in most cases, c.T. occasionally misses large subdural collections. Even in the preserce of a negative c.T. scan, further diagnostic measures should be undertaken if the clinical pic-
SiR,—Your editorial
ture so warrants.
Acute subdural hxmatomas generally present as high-density masses, while those in the chronic stages tend to have low density in the c.T. scan. During the transition from high to low density, these lesions may be isodense with respect to brain and, therefore, not visible. Isodense lesions can also occur during acute stages of subdural bleeding if the patient has a low hxmoglobin or if the bleeding occurs into a pre-existing chronic subdural collection. The frequency of isodense subdural hxmatomas on C.T. scanning has ranged from 7%2 to
17%.3 The presence of isodense lesions, if unilateral, can be inferred by the concomitant distortion of the ventricular system usually visible in the c.T. scan. All the isodense lesions observed by Galbraith et al. were unilateral and causing ventricular distortion. If the lesions are bilateral, however, the c.T. scan may show no evidence of any lesion. Unfortunately, bilateral subdural collections are far from rare. In one of the largest published series, they were found in 34% of all the patients with subdural hmmatomas.4 Although c.T. scanning can be of great assistance in the diagnosis of subdural hxmatoma, the possibility of false-negative results must not be overlooked. In one series5 4% of patients had a negative c.T. scan despite having subdural hxmatomas, proved by angiography or surgery. If a subdural hsematoma is suspected on clinical grounds, a negative c.T. scan should not rule against the possible use of exploratory burr holes or cerebal angiography in search for such lesion. Because of its non-invasive nature, however, c.T. scanning still is preferable to other more traditional diagnostic procedures as the initial, and possibly the only, test.
Neurology Service, Veterans Administration Hospital, Portland, Oregon 97201, U.S.A.
1. Lancet, 1978, ii, 1189. 2. Galbraith, S., Blaiklock, C. T.,
LUIS GARCIA-BUÑUEL
Jennett, B., Steven, J. L. Br. J Surg. 1976, 63, 157. 3. Kim, K. S., Hemmati, M., Weinberg, P. E. Radiology, 1978, 128, 71. 4. Dublin, A. B., French, B. M., Rennick, J. M. ibid. 1977,122, 365. 5. Forbes, G. S., Sheedy, P. F., Piepgrass, D. G., Houser, O. W. ibid. 1978, 126, 143.
Malignancy in general is associated with an increased prevalence of mycobacterial infection, and this can be attributed to impaired cellular immunity. This impairment is especially evident among the lymphoproliferative disorders, and is often compounded by cancer chemotherapy. With hairy-cell leukxmia, defective monocyte function and monocytopenia may be further relevant factors, as Weinstein et al. remarked. Most studies linking malignancy with mycobacteriosis have excluded infections with atypical organisms. Their relative importance was consequently unclear until the study of Feld and colleagues5 showed that atypical organisms were involved in 51% (30/59) of such cases. If these findings are corroborated, the possibility of an atypical, and hence drug-resistant, organism should be considered from the outset whenever acid-fast bacilli are found in such immunocompromised patients. This is well illustrated by our case, the patient dying shortly before drug insensitivity was confirmed. Divisions of Hematology/Oncology and Pulmonary Diseases,
Department of Medicine, Medical Center, University Hospital, Morgantown, West Virginia 26506,
U.S.A.
ALEX M. HENDRICK D. J. HENDRICK
CYCLOSPORIN A
SIR,-In
interesting pilot studies of the clinical use of published in your Dec. 23/30 issue, worrying
two
A side-effects were encountered which had not been seen in earlier animal experiments. As both groups of workers suggest, it is to be hoped that lower dosages of the drug will prove effectively immunosuppressant without interfering with hepatic and renal function. This problem can only be resolved when more is known about the uptake, distribution, and half-life of cyclosporin A in man, particularly when administered by mouth. Meantime, it may be worth trying to draw some tentative conclusions from the limited data available. Firstly, hepatic and renal disturbance of varying intensity has been encountered in most patients to whom the drug has been given, whether or not they have received allografts. The hepatic effects appear to be mild but directly related to cyclosporin-A administration and to dosage. Serum bilirubin, alkaline phosphatase, and alanine aminotransferase values are significantly raised but decline rapidly with reducing drug dosage and may even fall to normal within 24 h of abrupt drug withdrawal. Similarly, some renal disturbance has been observed in patients who previously had normal function; dysfunction appears to be dose related and rapidly reversible on withdrawal of cyclosporin A even in kidney-allografted patients
cyclosporin
2. Manes, J. L., Blair, O. M. J. Am. med. Ass. 1976, 236, 878. 3. Case Records of the Massachusetts General Hospital New Engl. J. Med. 1977, 296, 1218. 4. Caplan, M. H., Armstrong, D., Rosen, P., Cancer, 1974, 33, 850. 5. Feld, R., Bodey, G. P., Groschel, D. Archs intern. Med. 1976, 136, 67.
who have been anuric for several days. This, coupled with the surprisingly normal morphology demonstrated by the Cambridge group in biopsy material from non-functioning grafts, strongly suggests that cyclosporin A directly affects tubular cells without causing necrosis, and that dysfunction is unlikely to be caused by rejection or vascular defects. It is tempting to speculate that cyclosporin A is acting rather like a continuous overdose of antidiuretic hormone (A.D.H.). It is -after all a cyclic polypeptide which bears an admittedly superficial resemblance to A.D.H. This might promote conversion of A.T.P. to cyclic 3’,5’-A.M.P. and thence affect water permeability in the distal convolutions and collecting tubules. Perhaps selective binding to neurophysin-like proteins in the kidneys is a necessary precursor to this hormone-like activity. If this is the case, then it might be possible to counter the effect with other agents such as low dosages of corticosteroids and thus balance water permeability in the distal tubules. Division of Comparative Medicine, Clinical Research Centre, Harrow, Middlesex HA1 3UJ
C.
J. GREEN
COMPUTERISED TOMOGRAPHY AND SUBDURAL HÆMATOMAS on the prevention of secondary brain after head damage injury’ cites a paper by Galbraith et al. as evidence that computerised tomographic (c.T.) scanning is a reliable means of detecting subdural hxmatomas. While this is true in most cases, c.T. occasionally misses large subdural collections. Even in the preserce of a negative c.T. scan, further diagnostic measures should be undertaken if the clinical pic-
SiR,—Your editorial
ture so warrants.
Acute subdural hxmatomas generally present as high-density masses, while those in the chronic stages tend to have low density in the c.T. scan. During the transition from high to low density, these lesions may be isodense with respect to brain and, therefore, not visible. Isodense lesions can also occur during acute stages of subdural bleeding if the patient has a low hxmoglobin or if the bleeding occurs into a pre-existing chronic subdural collection. The frequency of isodense subdural hxmatomas on C.T. scanning has ranged from 7%2 to
17%.3 The presence of isodense lesions, if unilateral, can be inferred by the concomitant distortion of the ventricular system usually visible in the c.T. scan. All the isodense lesions observed by Galbraith et al. were unilateral and causing ventricular distortion. If the lesions are bilateral, however, the c.T. scan may show no evidence of any lesion. Unfortunately, bilateral subdural collections are far from rare. In one of the largest published series, they were found in 34% of all the patients with subdural hmmatomas.4 Although c.T. scanning can be of great assistance in the diagnosis of subdural hxmatoma, the possibility of false-negative results must not be overlooked. In one series5 4% of patients had a negative c.T. scan despite having subdural hxmatomas, proved by angiography or surgery. If a subdural hsematoma is suspected on clinical grounds, a negative c.T. scan should not rule against the possible use of exploratory burr holes or cerebal angiography in search for such lesion. Because of its non-invasive nature, however, c.T. scanning still is preferable to other more traditional diagnostic procedures as the initial, and possibly the only, test.
Neurology Service, Veterans Administration Hospital, Portland, Oregon 97201, U.S.A.
1. Lancet, 1978, ii, 1189. 2. Galbraith, S., Blaiklock, C. T.,
LUIS GARCIA-BUÑUEL
Jennett, B., Steven, J. L. Br. J Surg. 1976, 63, 157. 3. Kim, K. S., Hemmati, M., Weinberg, P. E. Radiology, 1978, 128, 71. 4. Dublin, A. B., French, B. M., Rennick, J. M. ibid. 1977,122, 365. 5. Forbes, G. S., Sheedy, P. F., Piepgrass, D. G., Houser, O. W. ibid. 1978, 126, 143.