667
Despair over the future NHS SIR,-Despite
all the debates and words written about the 1989
white-paper on the National Health Service few clinicians can yet judge whether this change in our way of working will or will not be the advantage of our patients. Many of us find ourselves becoming fellow travellers, largely because of the most profligate over-riding of the democratic process. At least [,40 million has been spent on establishing the new framework before the National Health Service Bill has been passed. Prof Harry Keen has tried his best to set this to rights and many of us wish him well, despite his failure (March 3, p 528). Despite the working-papers that followed publication of this ill-conceived white-paper we are still being told, when a self-evident problem is pointed out, that arrangements to deal with it will be to
later. I see no evidence that the accurate information system needed for an internal market will be in place by April, 1991. Nobody has defmed the validity of the "contracts" which supposedly control the exercise: where do they lie on the spectrum between a broad general agreement and a legally binding, precise contract? Just how profound the changes are came to me abruptly a few weeks ago, and I am still unable to come to terms with what was said to me. Our new regional general manager told me that if I wished to ensure proper funding for our district general hospital I must go to general practices on the boundaries of our district and sell my services: in other words, I advertise what I can offer by way of a consultant service. I told him that this was totally against the ethics of our profession. I imagine he simply thought me an old fool. The white-paper is really about rationing. No country can afford all that medical science can do for its people, and I suppose it was ever thus. Nevertheless in my youth we did see the promised land-one in which health care is a basic human right. The National Health Service is the greatest experiment in social equity that Britain has seen, and until the early 1970s it seemed to be a successful one. I have long been convinced that it was the oil crisis of those times that prevented its further development. The C40 million that has already been spent in the expectation that Parliament will pass the necessary legislation could, if allocated differently, have prevented the cut in services we have seen in the past few months. Will the money needed to construct an internal market make the NHS so much more efficient that less rationing will be required? Is the change so designed that the rich, through private insurance, will be able to obtain an unacceptable advantage in the restricted availability of health care? Will a two-tier system of NHS hospitals and general practices develop so that less privileged groups get less than their share? This is the first managerial revolution to imply a profound cultural change in medical practice-one that may alter the calibre and commitment of people who come into medicine. Throughout all the stresses and strains of the past 25 years the total commitment of junior colleagues to the concept of an NHS for all has been a great comfort to me. If I have ever detected any wavering it has related to private patients who come onto the general ward. If a different type of young person were to be attracted into medicine-one who was in it purely for financial reward-then indeed would my grey hairs be brought in sorrow to the grave.
published
Postgraduate Medical Centre, Salisbury General Infirmary, Salisbury, Wiltshire SP2 7SX, UK
P. M. S. GILLAM
Continued marketing of a useless (’Varidase’) in Panama
drug
SIR, The marketing of "Varidase’ (streptokinase/streptodornase; tablets in Central America exemplifies shared irresponsibility by manufacturers and drug regulators. The preparation is promotedl as an anti-inflammatory agent for trauma, abscesses, acute or chronic thrombophlebitis, cellulitis, sinusitis, haematomas, sprains, fractures, boils, acne, otitis, episiotomies, tooth extraction, and dental inflammatory processes. When given by mouth streptodornase is inactivated by the gastric fluid, and Lederle)
not absorbed2 Clinical efficacy has not been established and the use of this and other enzyme preparations (such as bromelains) have been considered of doubtful valued This enzyme combination product was voluntarily withdrawn from the USA by the manufacturer in 1981, but marketing in other countries, notably Panama, has continued. A re-evaluation of publications on varidase, supported by the recommendation of a US Food and Drug Administration task forced resulted in the withdrawal of varidase from Panama’s social security drug formulary by the medicines commission in 1986. Varidase purchases by the social security scheme, providing pharmaceuticals for 85% of the population, had amounted to $270 000 (0-7% of drug expenditure) in 1984. Although the head of the department of pharmacy and drugs of the Panama Ministry of Health was a member of the Medicines Commission at the time varidase was withdrawn from the formulary, the product was never withdrawn from the market, and when the licence expired in 1988 it was renewed. The continued marketing of this useless enzyme combination product is a clear example of double standards by a multinational drug company and of the unwillingness of health authorities in developing countries to live up to their responsibilities.
streptokinase is
Department of Pharmacology, Faculty of Medicine, University of Panama, Panama City, Panama, and Medicines Commission, Social Security Institute, Panama
DAVID LEE
1. Rosenstein E, ed. Diccionario de especialidades farmacéuticas, 18th ed. CAD Mexico.
2 3. 4. 5.
6.
Panamericana de Libros de Medicina, 1987. ed. Martindale: the extra pharmacopoeia, 28th ed. London: Pharmaceutical Press, 1982. Anon. Br Nat Formul 1985; no 10:325. Goodman LS, Gilman A, eds The pharmacological basis of therapeutics, 5th ed. New York: Macmillan, 1975. Modell W, ed. Drugs of choice 1972-1973. St Louis. CV Mosby, 1972. Anon Fed Reg 1985; (Dec 13):51102-04.
Reynolds JEF,
Evening primrose oil
and
eczema
SIR,-In your issue of Nov 25 (p 1261) Dr Wade and colleagues review the evidence drug companies use to justify advertising. Most doctors will be able to cite optimistic or exaggerated claims but we are especially concerned about ’Epogam’ (evening primrose oil; Scotia Pharmaceuticals). The promotional literature states that evening primrose oil produces "a substantial and highly significant clinical improvement" in atopic eczema. The active ingredient is claimed to be y-linolenic acid, a precursor of arachidonic acid and produced in man by the desaturation of the essential fatty acid linoleic acid. The company refers to eight placebo-controlled trials of epogam, four with a crossover design and four parallel studies (one study is cited separately for children and adults). The numbers of patients entering the studies are provided (202 in the crossover studies and 109 in the parallel studies), not the numbers completing the trials. Four studies are referenced as "data on file"; one reference is not to the results of a trial but to an account of therapeutic principles in atopic dermatitis;l only three have been published in refereed journals.2-4 Of the 311 patients entering trials cited as supporting epogam, for only 128 who completed trials have details been
published. No published trial yields a significant advantage of epogam over placebo in direct comparisons of dermatologists’ assessment of eczema. Eczema was assessed on 10 cm linear or 5 or 6 point scales for area, redness, scaling, and overall severity. In the parallel studies there was no significant difference although both active and placebo groups tended to improve.3,4 In the crossover study2 data are presented as changes from baseline rather than as actual scores, and the difference between placebo and epogam may have been due to different baseline scores, as happened in one of the parallel studies.3 A more meaningful comparison would have been between actual scores.
On these criteria
none
of the studies demonstrated
a
significant advantage of epogam over placebo in the clinical grading
668
of eczema. Onerecorded improvement in patients’ assessments of itch but the large difference in pre-trial scores between the groups makes interpretation difficult. Scotia Pharmaceuticals have given us details of two unpublished studies; neither shows a significant clinical difference between epogram and placebo. All the trials have been included in a meta-analysis,s originating from the Efamol Research Institute, which claimed very significant benefits for epogam in the treatment of eczema. The largest published trial was a double-blind crossover study completed by 123 patients with atopic eczema in which no significant effect of epogam was seen.6 The meta-analysis and the promotional literature reject these findings and suggest that placebo and epogam tablets were mixed, rendering the study void. Atopic eczema is a common and distressing condition, and the market for any potential treatment is huge. A safe oral treatment has obvious attractions. As for the evaluation of therapy in any chronic
relapsing disease, a double-blind, randomised, placebo-controlled parallel trial is the best study design. Such trials as have been done with epogam in atopic eczema do not show a significant advantage over placebo, and a meta-analysis is no more reliable than the data on which it is based. The claim of a "substantial and highly significant clinical improvement" is not substantiated. This should be considered before doctors put patients on a treatment for which even the manufacturers
to
recommend a treatment time of 8-12 weeks
achieve a benefit.
Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK
G. R. SHARPE P. M. FARR
Meigel W. Treatment of atopic dermatitis. Z Hautkr 1986; 61: 473-78. Wright S, Burton JL. Oral evening-primrose-seed oil improves atopic eczema. Lancet 1982; ii: 1220-22. 3. Schalin-Karrila M, Mattila L, Jansen CT, Uotila P. Evening primrose oil m the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol 1987; 117: 11-19. 4. Bordoni A, Biagi PL, Masi M, et al. Evening primrose oil (Efamol) in the treatment of children with atopic eczema. Drugs Exp Clin Res 1987; 14: 291-97. 5. Morse PF, Horrobin DF, Manku MS, et al. Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema: relationship between plasma essential fatty add changes and clinical response. Br J Dermatol 1989; 121: 75-90. 6. Bamford JTM, Gibson RW, Renier CM. Atopic eczema unresponsive to evening primrose oil (linoleic and &ggr;-linolenic acids). J Am Acad Dermatol 1985; 13: 959-65. 1.
2.
Pseudotumor cerebri associated with
leuprorelin acetate SIR,-Leuprorelin acetate is a synthetic nonapeptide analogue of naturally occurring gonadotropin releasing hormone (GnRH or LHRH) that is used in the treatment of sterility and advanced prostatic cancer. Its main side-effects include hot flushes, vaginal dryness, electrocardiographic changes, local wheal reactions, and peripheral oedema.1 We describe a patient in whom pseudotumor cerebri (benign increased intracranial pressure) developed during treatment with leuprorelin acetate agonist. A 33-year-old man with a long history of hypogonadism and azoospermia was admitted because of rheumatic fever. During the past 2 years, he had been placed on a pulsatile LHRH pump (’Lupron’) without improvement in his sterility. A year later, while still on leuprorelin acetate, the patient had severe constant headaches. On admission he had bilateral papilloedema. Neurological examination and computed tomography of brain were normal. The cerebrospinal fluid (CSF) was clear and acellular at a pressure of 429 mm H2O, within protein 17 mg/dl and glucose 51 mg/dl. Cultures for bacteria, viruses, and tuberculosis were negative. Visual field examination revealed slight bilateral nasal loss. No known
cause
of increased intracranial pressure
was
discontinuation of the drug. Transient frontal headaches have been frequently reported during treatment with another LHRH analogue.’ Pseudotumor cerebri is caused by several drugs, including tetracycline, steroids, vitamin A, nalidixic acid, nitrofurantoin, sulphur preparations, and phenytoin,
levothyroxine. Departments of Internal Medicine and Neurology, Beilinson Medical Centre, Petah Tiqva, Israel 49 100
N. ARBER R. FADILA J. PINKHAS
H. SHIRIN E. MELAMED Y. SIDI
GS, Coddington CC, Winkel CA, Shawker TH, Lonaux DL, Collins RL. Efficacy of a gonadotropin-releasing hormone agonist in the treatment of uterine leiomyomata. Fertil Steril 1989; 51: 951-56 2. Bowman MA. Pseudotumour cerebri. Am Fam Physician 1978; 35: 177-82. 3. Hoffman HJ. Pseudotumour cerebri. Surg Neurol 1987; 27: 405. 1 Letterie
Evidence for neoplasia in "pseudolymphoma" of lung SIR,-"Pseudolymphoma" is
a term
used
to
describe extranodal
tumour-like
lymphoid hyperplasia which is not clearly neoplastic histologically;’ its origin is uncertain. Our molecular genetic and cytogenetic studies in a case of pulmonary pseudolymphoma revealed the tumour to be neoplastic and of B-cell origin. A 43-year-old woman was admitted in December, 1988, for evaluation of slowly progressive lung disease which she had had for about 4 years. She had a history of left orbital tumour diagnosed histologically as a benign lymphoid hyperplasia in March, 1988. Chest X-rays revealed nodular shadows in the bilateral lower lung fields but there was no evidence of tumour involvement in other regions. She had autoimmune haemolytic anaemia (Hb 97 g/dl, haptoglobin 3-1 mg/dl, direct and indirect Coombs’ test positive); the gammaglobulin level was normal. In February, 1989, she underwent right lower lobectomy with removal of the tumour, which was histologically compatible with pseudolymphoma.1 Immunophenotypic findings on fresh excised tumour cells indicated polyclonal lymphoid hyperplasia. Studies of tumour DNA by Southern hybridisation with JH, JK, Cp, and Jyl probes revealed clonal rearrangements of Ig heavy-chain and kappa-chain genes (fig 1). Cytogenetic study after short-term culture of tumour cells without mitogens revealed, in the 11 metaphases studied, 7 normal diploid and 4 hyperdiploid patterns. +3, +7, lp+, and +mar2 were common constitutional abnormalities in 4 hyperdiploid metaphases (fig 2), that consisted of 49-50 chromosomes with minor karyotypic instabilities. Although some studies of extranodal lymphoid hyperplasias have revealed clonal Ig rearrangements2-4 this is not direct evidence of malignancy, and no cytogenetic study has been reported so far. The
found.
Leuprorelin acetate was discontinued. On follow-up the papilloedema resolved and headaches and visual-field defects subsided. Six months later, he had a normal CSF pressure of 180 H2O. Neurological and fundoscopic examinations were normal 30 months later. Headaches did not recur. We believe that leuprorelin acetate was responsible for the emergence of pseudotumor cerebri in our patient. There is no reported association between rheumatic fever and pseudotumor became normal Intracranial after cerebri.2,3 pressure
mm
Fig 1-Southern hybridisation analysis of DNA from tumour. - =germlme band position,
Despair over the future NHS SIR,-Despite
all the debates and words written about the 1989
white-paper on the National Health Service few clinicians can yet judge whether this change in our way of working will or will not be the advantage of our patients. Many of us find ourselves becoming fellow travellers, largely because of the most profligate over-riding of the democratic process. At least [,40 million has been spent on establishing the new framework before the National Health Service Bill has been passed. Prof Harry Keen has tried his best to set this to rights and many of us wish him well, despite his failure (March 3, p 528). Despite the working-papers that followed publication of this ill-conceived white-paper we are still being told, when a self-evident problem is pointed out, that arrangements to deal with it will be to
later. I see no evidence that the accurate information system needed for an internal market will be in place by April, 1991. Nobody has defmed the validity of the "contracts" which supposedly control the exercise: where do they lie on the spectrum between a broad general agreement and a legally binding, precise contract? Just how profound the changes are came to me abruptly a few weeks ago, and I am still unable to come to terms with what was said to me. Our new regional general manager told me that if I wished to ensure proper funding for our district general hospital I must go to general practices on the boundaries of our district and sell my services: in other words, I advertise what I can offer by way of a consultant service. I told him that this was totally against the ethics of our profession. I imagine he simply thought me an old fool. The white-paper is really about rationing. No country can afford all that medical science can do for its people, and I suppose it was ever thus. Nevertheless in my youth we did see the promised land-one in which health care is a basic human right. The National Health Service is the greatest experiment in social equity that Britain has seen, and until the early 1970s it seemed to be a successful one. I have long been convinced that it was the oil crisis of those times that prevented its further development. The C40 million that has already been spent in the expectation that Parliament will pass the necessary legislation could, if allocated differently, have prevented the cut in services we have seen in the past few months. Will the money needed to construct an internal market make the NHS so much more efficient that less rationing will be required? Is the change so designed that the rich, through private insurance, will be able to obtain an unacceptable advantage in the restricted availability of health care? Will a two-tier system of NHS hospitals and general practices develop so that less privileged groups get less than their share? This is the first managerial revolution to imply a profound cultural change in medical practice-one that may alter the calibre and commitment of people who come into medicine. Throughout all the stresses and strains of the past 25 years the total commitment of junior colleagues to the concept of an NHS for all has been a great comfort to me. If I have ever detected any wavering it has related to private patients who come onto the general ward. If a different type of young person were to be attracted into medicine-one who was in it purely for financial reward-then indeed would my grey hairs be brought in sorrow to the grave.
published
Postgraduate Medical Centre, Salisbury General Infirmary, Salisbury, Wiltshire SP2 7SX, UK
P. M. S. GILLAM
Continued marketing of a useless (’Varidase’) in Panama
drug
SIR, The marketing of "Varidase’ (streptokinase/streptodornase; tablets in Central America exemplifies shared irresponsibility by manufacturers and drug regulators. The preparation is promotedl as an anti-inflammatory agent for trauma, abscesses, acute or chronic thrombophlebitis, cellulitis, sinusitis, haematomas, sprains, fractures, boils, acne, otitis, episiotomies, tooth extraction, and dental inflammatory processes. When given by mouth streptodornase is inactivated by the gastric fluid, and Lederle)
not absorbed2 Clinical efficacy has not been established and the use of this and other enzyme preparations (such as bromelains) have been considered of doubtful valued This enzyme combination product was voluntarily withdrawn from the USA by the manufacturer in 1981, but marketing in other countries, notably Panama, has continued. A re-evaluation of publications on varidase, supported by the recommendation of a US Food and Drug Administration task forced resulted in the withdrawal of varidase from Panama’s social security drug formulary by the medicines commission in 1986. Varidase purchases by the social security scheme, providing pharmaceuticals for 85% of the population, had amounted to $270 000 (0-7% of drug expenditure) in 1984. Although the head of the department of pharmacy and drugs of the Panama Ministry of Health was a member of the Medicines Commission at the time varidase was withdrawn from the formulary, the product was never withdrawn from the market, and when the licence expired in 1988 it was renewed. The continued marketing of this useless enzyme combination product is a clear example of double standards by a multinational drug company and of the unwillingness of health authorities in developing countries to live up to their responsibilities.
streptokinase is
Department of Pharmacology, Faculty of Medicine, University of Panama, Panama City, Panama, and Medicines Commission, Social Security Institute, Panama
DAVID LEE
1. Rosenstein E, ed. Diccionario de especialidades farmacéuticas, 18th ed. CAD Mexico.
2 3. 4. 5.
6.
Panamericana de Libros de Medicina, 1987. ed. Martindale: the extra pharmacopoeia, 28th ed. London: Pharmaceutical Press, 1982. Anon. Br Nat Formul 1985; no 10:325. Goodman LS, Gilman A, eds The pharmacological basis of therapeutics, 5th ed. New York: Macmillan, 1975. Modell W, ed. Drugs of choice 1972-1973. St Louis. CV Mosby, 1972. Anon Fed Reg 1985; (Dec 13):51102-04.
Reynolds JEF,
Evening primrose oil
and
eczema
SIR,-In your issue of Nov 25 (p 1261) Dr Wade and colleagues review the evidence drug companies use to justify advertising. Most doctors will be able to cite optimistic or exaggerated claims but we are especially concerned about ’Epogam’ (evening primrose oil; Scotia Pharmaceuticals). The promotional literature states that evening primrose oil produces "a substantial and highly significant clinical improvement" in atopic eczema. The active ingredient is claimed to be y-linolenic acid, a precursor of arachidonic acid and produced in man by the desaturation of the essential fatty acid linoleic acid. The company refers to eight placebo-controlled trials of epogam, four with a crossover design and four parallel studies (one study is cited separately for children and adults). The numbers of patients entering the studies are provided (202 in the crossover studies and 109 in the parallel studies), not the numbers completing the trials. Four studies are referenced as "data on file"; one reference is not to the results of a trial but to an account of therapeutic principles in atopic dermatitis;l only three have been published in refereed journals.2-4 Of the 311 patients entering trials cited as supporting epogam, for only 128 who completed trials have details been
published. No published trial yields a significant advantage of epogam over placebo in direct comparisons of dermatologists’ assessment of eczema. Eczema was assessed on 10 cm linear or 5 or 6 point scales for area, redness, scaling, and overall severity. In the parallel studies there was no significant difference although both active and placebo groups tended to improve.3,4 In the crossover study2 data are presented as changes from baseline rather than as actual scores, and the difference between placebo and epogam may have been due to different baseline scores, as happened in one of the parallel studies.3 A more meaningful comparison would have been between actual scores.
On these criteria
none
of the studies demonstrated
a
significant advantage of epogam over placebo in the clinical grading
668
of eczema. Onerecorded improvement in patients’ assessments of itch but the large difference in pre-trial scores between the groups makes interpretation difficult. Scotia Pharmaceuticals have given us details of two unpublished studies; neither shows a significant clinical difference between epogram and placebo. All the trials have been included in a meta-analysis,s originating from the Efamol Research Institute, which claimed very significant benefits for epogam in the treatment of eczema. The largest published trial was a double-blind crossover study completed by 123 patients with atopic eczema in which no significant effect of epogam was seen.6 The meta-analysis and the promotional literature reject these findings and suggest that placebo and epogam tablets were mixed, rendering the study void. Atopic eczema is a common and distressing condition, and the market for any potential treatment is huge. A safe oral treatment has obvious attractions. As for the evaluation of therapy in any chronic
relapsing disease, a double-blind, randomised, placebo-controlled parallel trial is the best study design. Such trials as have been done with epogam in atopic eczema do not show a significant advantage over placebo, and a meta-analysis is no more reliable than the data on which it is based. The claim of a "substantial and highly significant clinical improvement" is not substantiated. This should be considered before doctors put patients on a treatment for which even the manufacturers
to
recommend a treatment time of 8-12 weeks
achieve a benefit.
Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK
G. R. SHARPE P. M. FARR
Meigel W. Treatment of atopic dermatitis. Z Hautkr 1986; 61: 473-78. Wright S, Burton JL. Oral evening-primrose-seed oil improves atopic eczema. Lancet 1982; ii: 1220-22. 3. Schalin-Karrila M, Mattila L, Jansen CT, Uotila P. Evening primrose oil m the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins. Br J Dermatol 1987; 117: 11-19. 4. Bordoni A, Biagi PL, Masi M, et al. Evening primrose oil (Efamol) in the treatment of children with atopic eczema. Drugs Exp Clin Res 1987; 14: 291-97. 5. Morse PF, Horrobin DF, Manku MS, et al. Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema: relationship between plasma essential fatty add changes and clinical response. Br J Dermatol 1989; 121: 75-90. 6. Bamford JTM, Gibson RW, Renier CM. Atopic eczema unresponsive to evening primrose oil (linoleic and &ggr;-linolenic acids). J Am Acad Dermatol 1985; 13: 959-65. 1.
2.
Pseudotumor cerebri associated with
leuprorelin acetate SIR,-Leuprorelin acetate is a synthetic nonapeptide analogue of naturally occurring gonadotropin releasing hormone (GnRH or LHRH) that is used in the treatment of sterility and advanced prostatic cancer. Its main side-effects include hot flushes, vaginal dryness, electrocardiographic changes, local wheal reactions, and peripheral oedema.1 We describe a patient in whom pseudotumor cerebri (benign increased intracranial pressure) developed during treatment with leuprorelin acetate agonist. A 33-year-old man with a long history of hypogonadism and azoospermia was admitted because of rheumatic fever. During the past 2 years, he had been placed on a pulsatile LHRH pump (’Lupron’) without improvement in his sterility. A year later, while still on leuprorelin acetate, the patient had severe constant headaches. On admission he had bilateral papilloedema. Neurological examination and computed tomography of brain were normal. The cerebrospinal fluid (CSF) was clear and acellular at a pressure of 429 mm H2O, within protein 17 mg/dl and glucose 51 mg/dl. Cultures for bacteria, viruses, and tuberculosis were negative. Visual field examination revealed slight bilateral nasal loss. No known
cause
of increased intracranial pressure
was
discontinuation of the drug. Transient frontal headaches have been frequently reported during treatment with another LHRH analogue.’ Pseudotumor cerebri is caused by several drugs, including tetracycline, steroids, vitamin A, nalidixic acid, nitrofurantoin, sulphur preparations, and phenytoin,
levothyroxine. Departments of Internal Medicine and Neurology, Beilinson Medical Centre, Petah Tiqva, Israel 49 100
N. ARBER R. FADILA J. PINKHAS
H. SHIRIN E. MELAMED Y. SIDI
GS, Coddington CC, Winkel CA, Shawker TH, Lonaux DL, Collins RL. Efficacy of a gonadotropin-releasing hormone agonist in the treatment of uterine leiomyomata. Fertil Steril 1989; 51: 951-56 2. Bowman MA. Pseudotumour cerebri. Am Fam Physician 1978; 35: 177-82. 3. Hoffman HJ. Pseudotumour cerebri. Surg Neurol 1987; 27: 405. 1 Letterie
Evidence for neoplasia in "pseudolymphoma" of lung SIR,-"Pseudolymphoma" is
a term
used
to
describe extranodal
tumour-like
lymphoid hyperplasia which is not clearly neoplastic histologically;’ its origin is uncertain. Our molecular genetic and cytogenetic studies in a case of pulmonary pseudolymphoma revealed the tumour to be neoplastic and of B-cell origin. A 43-year-old woman was admitted in December, 1988, for evaluation of slowly progressive lung disease which she had had for about 4 years. She had a history of left orbital tumour diagnosed histologically as a benign lymphoid hyperplasia in March, 1988. Chest X-rays revealed nodular shadows in the bilateral lower lung fields but there was no evidence of tumour involvement in other regions. She had autoimmune haemolytic anaemia (Hb 97 g/dl, haptoglobin 3-1 mg/dl, direct and indirect Coombs’ test positive); the gammaglobulin level was normal. In February, 1989, she underwent right lower lobectomy with removal of the tumour, which was histologically compatible with pseudolymphoma.1 Immunophenotypic findings on fresh excised tumour cells indicated polyclonal lymphoid hyperplasia. Studies of tumour DNA by Southern hybridisation with JH, JK, Cp, and Jyl probes revealed clonal rearrangements of Ig heavy-chain and kappa-chain genes (fig 1). Cytogenetic study after short-term culture of tumour cells without mitogens revealed, in the 11 metaphases studied, 7 normal diploid and 4 hyperdiploid patterns. +3, +7, lp+, and +mar2 were common constitutional abnormalities in 4 hyperdiploid metaphases (fig 2), that consisted of 49-50 chromosomes with minor karyotypic instabilities. Although some studies of extranodal lymphoid hyperplasias have revealed clonal Ig rearrangements2-4 this is not direct evidence of malignancy, and no cytogenetic study has been reported so far. The
found.
Leuprorelin acetate was discontinued. On follow-up the papilloedema resolved and headaches and visual-field defects subsided. Six months later, he had a normal CSF pressure of 180 H2O. Neurological and fundoscopic examinations were normal 30 months later. Headaches did not recur. We believe that leuprorelin acetate was responsible for the emergence of pseudotumor cerebri in our patient. There is no reported association between rheumatic fever and pseudotumor became normal Intracranial after cerebri.2,3 pressure
mm
Fig 1-Southern hybridisation analysis of DNA from tumour. - =germlme band position,
