947
because in several patients increasing from 3 x4 mg to 3 x 8 mg daily seemed to improve the antiemetic effect. PCP is well described in patients receiving intensive
chemotherapy including prolonged high-dose steroids,2 usually
as
part of the management of high-grade lymphomas, and cotrimoxazole prophylaxis is a routine part of treatment in these
patients. However, PCP as a complication of antiemetic therapy is less well recognised. EMA/CO results in consistent but manageable
myelosuppression and since the appearance of 2 cases of PCP-like infections coincided with an increase in the dose of dexamethasone used we think it likely that these two episodes were due to the high steroid exposure resulting from the regular weekly chemotherapy. In the two studies recently reported chemotherapy was administered with 14 or 21 day intervals, providing an average dose of 24 and 18 mg dexamethasone, respectively, per week compared with 48 mg per week for patients receiving EMA/CO. When intensive weekly chemotherapy regimens of this type are being used there is thus a strong case for using non-steroid antiemetic prophylaxis (eg, domperidone, prochloperazine,
PDGF.6 This might enhance the effect of PDGF released from platelet plugs both in the clubbed finger and the arterial wall. Since platelet changes are determined in the megakaryocyte a study of the biology of this cell might help to explain many vascular changes, including those in clubbing.
J. F. M. is Bntish Heart Foundation professor of Cardiovascular Science. Department of Medicine, King’s College School of Medicine and Dentistry, London SE5 9PJ, UK University Department of
2. 3.
5.
London W6 8RF, UK
1. Newlands ES, Bagshawe
KD, Begent RHJ, Rustin GJS, Holden L. Results with the EMA/CO regimen in high nsk gestational trophoblastic rumours, 1979-1989. Br J Obstet Gynaecol 1991; 98: 550-57. 2. Browne M, Hubbard SM, Longo DL, et al. Excess prevalence of Pneumocystis carinii pneumonia in lymphoma patients receiving chemotherapy Ann Intern Med 1986; 104: 338-44.
Finger clubbing SIR,-For finger clubbing has been a sign without a pathophysiological meaning. Fox and colleagues’ finding (Aug 3, p 313) that the capillaries in clubbed fmgers contain material that is antigenically positive for platelets supports Dickinson and Martin’s1 hypothesis that platelet-derived growth factor (PDGF) liberated from megakaryocytes and platelet clumps was responsible for the cellular hyperplasia. This has several implications. Firstly, clubbing has become a sign of a change in the megakaryocyte-platelet axis. Our data show that megakaryocytes are larger in patients with carcinoma of the lung than in controls.2 Platelets have no nuclei and only residual amounts of mRNA. Platelet PDGF is determined by megakaryocyte mRNA for PDGFTherefore, clubbing might be a sign of altered synthetic capacity by megakaryocytes in carcinoma of the lung (and other diseases where it occurs). Secondly, Fox and colleagues’ finding is indirect evidence that platelet production results from fragmentation of megakaryocyte cytoplasm in the pulmonary circulation.’ In clubbing one could postulate that activated megakaryocytes and megakaryocyte cytoplasmic particles pass from the pulmonary arterial circulation into the systemic circulation via abnormal circulation around lung tumours or chronic pulmonary inflammation. In cyanotic congenital heart disease, this may occur via right to left shunts. Thirdly, their finding might throw some light on the role of platelets in atherogenesis. Atherosclerosis is a proliferative disease of the vessel wall in which PDGF has been implicated. Evidence has been presented that the initial arterial wall proliferation is secondary to the occlusion by platelets of vasa vasorum in the vessel wall. These vessels are the same size as those Fox and colleagues found to contain platelets in clubbing. If release of PDGF from platelets in such vessels can cause cellular hyperplasia in finger clubbing, then analogous changes might occur in the arterial wall secondary to release of PDGF from platelets occluding the microcirculation of the vessel wall. Hypoxia of tissue distal to occlusion of the microcirculation with platelets will probably arise. Exposure of cultured cells to hypoxia can cause an increase in their production of mRNA for several centuries
CJ, Martin JF. Megakaryocytes and platelet clumps as the course of finger clubbing. Lancet 1987; ii: 1434-35. Knstensen SD, Bath PMW, Gladwin AM, Thorpe JAC, Martin JF. Increased megakaryocyte size in bronchial carcinoma Eur J Clin Invest 1989; 19: A5. Gladwin AM, Carrier MJ, Beesley JE, Lelchuk R, Hancock, Martin JF. Identification of mRNA for PDGF B-chain in human megakarycoytes isolated using a novel immunomagnetic separation method. Br JHaematol 1990; 76: 333-39. Martin JF, Levine RF. Evidence in favour of the lungs and against the bone marrow as the site of platelet production. In: Page CP, ed. The platelet in health and disease. Oxford: Blackwell Scientific Publications, 1991: 1-9. Martin JF, Booth RG, Moncada S. Arterial wall hypoxia following thrombosis of the vasa vasorum is an initial lesion in atherosclerosis Eur J Clin Invest 1991; 21:
1. Dickinson
4.
Department of Medical Oncology, Charing Cross Hospital,
STEEN D. KRISTENSEN
Aarhus, Denmark
ondansetron)
KIERAN MCCORMACK GORDON J. S. RUSTIN DAVID B. SMITH E. S. NEWLANDS
Cardiology,
Skejby Hospital,
and adding dexamethasone only if the emesis is very difficult to control. Prophylactic co-trimoxazole in conjunction with dexamethasone may also be considered but is not used with EMA/CO because of the potential interaction with methotrexate.
or
JOHN F. MARTIN
355-59. 6. Sakanassen KS, Powell JS, Raines EW, Ross R. Selective expression of platelet denved growth factor B-chain mRNA by human endothelial cells and by human peripheral blood monocytes but not by smooth muscle cells. Thromb Haemost 1987; 58: 261.
Alfuzosin for
benign prostatic hypertrophy
SIR,-Mr C:happle (July 20, p 182), commenting on our report (June 15, p 1457) of alfuzosin, a novel a1-blocker, in benign prostatic hypertrophy (BPH), records his own experience with prazosin. There is now little doubt that al-blockade with several agents such as alfuzosin, doxazosin, indoramin, prazosin, terazosin, and YM 617, can afford measurable relief to many patients with BPH: however, xl-blockers do not seem to reverse permanently the pathophysiology of BPH. It has been suggested that about 40 per 100 patients who do not need surgery can be maintained indefinitely on medical treatment; because their condition is not progressive, such patients may reach a certain stage, thereafter remaining stable.l,2. Our study only partly answered the questions of long-term treatment with an oc,-blocker, since an improvement in voiding symptoms was seen after 6 months of alfuzosin. In fact, this improvement was maintained in patients who continued alfuzosin in an open study, up to 12 months (n =121 ), 18 months (n=56), 24 months (n = 45), and 30 months (n= 19) (unpublished data), without the development of tolerance or side-effects due to long-term administration. Since candidates for
in BPH may need treatment for many years, the response to and compliance with such drugs remain critical issues; furthermore, the notion of long-term treatment in BPH has to be defmed.
crl-blockade
long-term
Service of Urology, Hôpital de Bicêtre, 94270 Kremlin-Bicêtre, France
H. BENSADOUN
Synthelabo Recherche, Paris
M. C. DELAUCHE-CAVALLIER P. ATTALI
A. JARDIN
1. Caine M. Alpha-adrenergic blocker for the treatment of benign prostatic hyperplasia.
Urol Clin North Am 1990; 17: 641-49. 2. Ball AJ, Feneley RCL, Abrams PH. The Br J Urol 1981; 53: 613-16.
natural history of untreated "prostatism".
Monitoring TURP SIR,-In your Sept 7 editorial you note that none of the methods used to detect irrigation fluid absorption-from use of radioisotopes to monitoring changes in serum sodium-have found general favour in urological practice. The breath alcohol method correlates well with changes in serum sodium, but neither detects acute perivesical absorption. Continuous sodium monitoring with an intravenously placed electrode is technically insufficiently reliable.’ New portable blood gas and electrolyte analysers giving results in 90 s with 250 III whole blood samples can be used in operating theatres and allow the convenient measurement of whole blood sodium
because in several patients increasing from 3 x4 mg to 3 x 8 mg daily seemed to improve the antiemetic effect. PCP is well described in patients receiving intensive
chemotherapy including prolonged high-dose steroids,2 usually
as
part of the management of high-grade lymphomas, and cotrimoxazole prophylaxis is a routine part of treatment in these
patients. However, PCP as a complication of antiemetic therapy is less well recognised. EMA/CO results in consistent but manageable
myelosuppression and since the appearance of 2 cases of PCP-like infections coincided with an increase in the dose of dexamethasone used we think it likely that these two episodes were due to the high steroid exposure resulting from the regular weekly chemotherapy. In the two studies recently reported chemotherapy was administered with 14 or 21 day intervals, providing an average dose of 24 and 18 mg dexamethasone, respectively, per week compared with 48 mg per week for patients receiving EMA/CO. When intensive weekly chemotherapy regimens of this type are being used there is thus a strong case for using non-steroid antiemetic prophylaxis (eg, domperidone, prochloperazine,
PDGF.6 This might enhance the effect of PDGF released from platelet plugs both in the clubbed finger and the arterial wall. Since platelet changes are determined in the megakaryocyte a study of the biology of this cell might help to explain many vascular changes, including those in clubbing.
J. F. M. is Bntish Heart Foundation professor of Cardiovascular Science. Department of Medicine, King’s College School of Medicine and Dentistry, London SE5 9PJ, UK University Department of
2. 3.
5.
London W6 8RF, UK
1. Newlands ES, Bagshawe
KD, Begent RHJ, Rustin GJS, Holden L. Results with the EMA/CO regimen in high nsk gestational trophoblastic rumours, 1979-1989. Br J Obstet Gynaecol 1991; 98: 550-57. 2. Browne M, Hubbard SM, Longo DL, et al. Excess prevalence of Pneumocystis carinii pneumonia in lymphoma patients receiving chemotherapy Ann Intern Med 1986; 104: 338-44.
Finger clubbing SIR,-For finger clubbing has been a sign without a pathophysiological meaning. Fox and colleagues’ finding (Aug 3, p 313) that the capillaries in clubbed fmgers contain material that is antigenically positive for platelets supports Dickinson and Martin’s1 hypothesis that platelet-derived growth factor (PDGF) liberated from megakaryocytes and platelet clumps was responsible for the cellular hyperplasia. This has several implications. Firstly, clubbing has become a sign of a change in the megakaryocyte-platelet axis. Our data show that megakaryocytes are larger in patients with carcinoma of the lung than in controls.2 Platelets have no nuclei and only residual amounts of mRNA. Platelet PDGF is determined by megakaryocyte mRNA for PDGFTherefore, clubbing might be a sign of altered synthetic capacity by megakaryocytes in carcinoma of the lung (and other diseases where it occurs). Secondly, Fox and colleagues’ finding is indirect evidence that platelet production results from fragmentation of megakaryocyte cytoplasm in the pulmonary circulation.’ In clubbing one could postulate that activated megakaryocytes and megakaryocyte cytoplasmic particles pass from the pulmonary arterial circulation into the systemic circulation via abnormal circulation around lung tumours or chronic pulmonary inflammation. In cyanotic congenital heart disease, this may occur via right to left shunts. Thirdly, their finding might throw some light on the role of platelets in atherogenesis. Atherosclerosis is a proliferative disease of the vessel wall in which PDGF has been implicated. Evidence has been presented that the initial arterial wall proliferation is secondary to the occlusion by platelets of vasa vasorum in the vessel wall. These vessels are the same size as those Fox and colleagues found to contain platelets in clubbing. If release of PDGF from platelets in such vessels can cause cellular hyperplasia in finger clubbing, then analogous changes might occur in the arterial wall secondary to release of PDGF from platelets occluding the microcirculation of the vessel wall. Hypoxia of tissue distal to occlusion of the microcirculation with platelets will probably arise. Exposure of cultured cells to hypoxia can cause an increase in their production of mRNA for several centuries
CJ, Martin JF. Megakaryocytes and platelet clumps as the course of finger clubbing. Lancet 1987; ii: 1434-35. Knstensen SD, Bath PMW, Gladwin AM, Thorpe JAC, Martin JF. Increased megakaryocyte size in bronchial carcinoma Eur J Clin Invest 1989; 19: A5. Gladwin AM, Carrier MJ, Beesley JE, Lelchuk R, Hancock, Martin JF. Identification of mRNA for PDGF B-chain in human megakarycoytes isolated using a novel immunomagnetic separation method. Br JHaematol 1990; 76: 333-39. Martin JF, Levine RF. Evidence in favour of the lungs and against the bone marrow as the site of platelet production. In: Page CP, ed. The platelet in health and disease. Oxford: Blackwell Scientific Publications, 1991: 1-9. Martin JF, Booth RG, Moncada S. Arterial wall hypoxia following thrombosis of the vasa vasorum is an initial lesion in atherosclerosis Eur J Clin Invest 1991; 21:
1. Dickinson
4.
Department of Medical Oncology, Charing Cross Hospital,
STEEN D. KRISTENSEN
Aarhus, Denmark
ondansetron)
KIERAN MCCORMACK GORDON J. S. RUSTIN DAVID B. SMITH E. S. NEWLANDS
Cardiology,
Skejby Hospital,
and adding dexamethasone only if the emesis is very difficult to control. Prophylactic co-trimoxazole in conjunction with dexamethasone may also be considered but is not used with EMA/CO because of the potential interaction with methotrexate.
or
JOHN F. MARTIN
355-59. 6. Sakanassen KS, Powell JS, Raines EW, Ross R. Selective expression of platelet denved growth factor B-chain mRNA by human endothelial cells and by human peripheral blood monocytes but not by smooth muscle cells. Thromb Haemost 1987; 58: 261.
Alfuzosin for
benign prostatic hypertrophy
SIR,-Mr C:happle (July 20, p 182), commenting on our report (June 15, p 1457) of alfuzosin, a novel a1-blocker, in benign prostatic hypertrophy (BPH), records his own experience with prazosin. There is now little doubt that al-blockade with several agents such as alfuzosin, doxazosin, indoramin, prazosin, terazosin, and YM 617, can afford measurable relief to many patients with BPH: however, xl-blockers do not seem to reverse permanently the pathophysiology of BPH. It has been suggested that about 40 per 100 patients who do not need surgery can be maintained indefinitely on medical treatment; because their condition is not progressive, such patients may reach a certain stage, thereafter remaining stable.l,2. Our study only partly answered the questions of long-term treatment with an oc,-blocker, since an improvement in voiding symptoms was seen after 6 months of alfuzosin. In fact, this improvement was maintained in patients who continued alfuzosin in an open study, up to 12 months (n =121 ), 18 months (n=56), 24 months (n = 45), and 30 months (n= 19) (unpublished data), without the development of tolerance or side-effects due to long-term administration. Since candidates for
in BPH may need treatment for many years, the response to and compliance with such drugs remain critical issues; furthermore, the notion of long-term treatment in BPH has to be defmed.
crl-blockade
long-term
Service of Urology, Hôpital de Bicêtre, 94270 Kremlin-Bicêtre, France
H. BENSADOUN
Synthelabo Recherche, Paris
M. C. DELAUCHE-CAVALLIER P. ATTALI
A. JARDIN
1. Caine M. Alpha-adrenergic blocker for the treatment of benign prostatic hyperplasia.
Urol Clin North Am 1990; 17: 641-49. 2. Ball AJ, Feneley RCL, Abrams PH. The Br J Urol 1981; 53: 613-16.
natural history of untreated "prostatism".
Monitoring TURP SIR,-In your Sept 7 editorial you note that none of the methods used to detect irrigation fluid absorption-from use of radioisotopes to monitoring changes in serum sodium-have found general favour in urological practice. The breath alcohol method correlates well with changes in serum sodium, but neither detects acute perivesical absorption. Continuous sodium monitoring with an intravenously placed electrode is technically insufficiently reliable.’ New portable blood gas and electrolyte analysers giving results in 90 s with 250 III whole blood samples can be used in operating theatres and allow the convenient measurement of whole blood sodium
