1552
lymphocytic inflammatory cell infiltration, and neuronal loss with gliosis. White matter was widely affected in 1 patient. Inclusion bodies were not present and electronmicroscopy did not show viral particles. With standard immunohistochemical techniques and mouse monoclonal anti-CMV (Dako) we could not demonstrate CMV antigen, a result similar to that obtained by Power et al.l Using in-situ hybridisation and a biotinylated CMV-DNA probe (Enzo Biochem, New York) with appropriate positive and negative controls
we
could
not
detect CMV nucleic acid in three
representative sections of brain tissue derived from each of 3 patients (total nine sections).3 The CMV probe was derived from a mixture of two clones of CMV sequences, one cloned into the Bam HI site of pIB176 and the other cloned into the Bam HI site of pUC18. This negative result is at variance with the widespread CMV positivity that Power et all obtained in 7 of 10 patients. The presence of Epstein-Barr virus (EBV) in RE brain tissue has been reported previously.’ In view of these discordant results it is possible that RE is an aetiologically diverse disorder in which the fairly uniform clinicopathological features represent the terminal stage of expression of various viral brain infections that include CMV, and others yet to be described. In agreement with Power et all about the need to pursue more convincing evidence of CMV causation we now routinely set up viral cultures on all resected RE brain tissue. Finally, there remains the possibility of viral triggering of an autoimmune mechanism of cortical and white matter destruction in which the initiating virus is no longer detectable by any of the above techniques. Such a hypothesis would be in keeping with the previous demonstration of immune complexes in RE brain tissue5 and would help to explain further the initially positive and subsequently negative CMV in-situ hybridisation study in one of Power and colleagues’ patients.
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
M. A. FARRELL L. CHENG M. E. CORNFORD W. W. GRODY H. V. VINTERS
C, Poland SD, Blume WT, et al. Cytomegalovirus and Rasmussen’s encephalitis. Lancet 1990; 336: 1282-84. 2. Rasmussen T, Andermann F. Update on the syndrome of "chronic encephalitis" and epilepsy. Cleveland Clin J Med 1989; 56 (suppl 2): S181-84. 3. Vinters HV, Kwok MK, Ho HW, et al. Cytomegalovirus in the nervous system of patients with the acquired immune deficiency syndrome. Brain 1989; 112: 245-68. 4. Walter FG, Renella RR. Epstein-Barr virus in brain and Rasmussen’s encephalitis. 1. Power
Lancet 1989; i: 279-80. 5. Andrews JM, Thompson JA, Pysher TJ, et al. Chronic encephalitis, epilepsy and cerebrovascular immune complex deposits. Ann Neurol 1990; 28: 88-90
Papaverine, benzodiazepines, and prolonged erections SIR,—The application of intracavernosal drugs to the diagnosis and treatment of erectile dysfunction has gained increasing acceptance since the chance finding in 1977 that papaverine injected into the corpus cavernosum could produce an erection.1 Although generally free from systemic side-effects, prolonged erection is an inevitable risk if a patient’s detumescence mechanisms cannot overcome the action of the drug. We have recently seen 2 patients who showed an interesting association between prolonged erections and simultaneous benzodiazepine and papaverine. A 47-year-old man with a history of erectile failure over several years, despite normal early morning erections, had a normal physical examination and hormonal screen. Before an intracavernosal test dose of 60 mg papaverine, 10 mg of diazepam was given intravenously because of patient anxiety. A full erection was achieved but persisted six h after injection. Despite instruction to return for pharmacological reversal, he attended his local accident and emergency centre, where ice-packs were applied until detumescence took place. A 30-year-old man with normal early morning erections in the absence of any other findings of impotence was diagnosed as having psychogenic erectile failure. Papaverine-stimulated colour doppler studies were completed with 60 mg papaverine; before papaverine injection, 5 mg diazepam was given intravenously because of patient
The doppler study showed an excellent arterial response with no evidence of a venous leak, but full erection persisted five h later and intracavernosal noradrenaline was necessary to reduce it. Both patients had prolonged erections after both diazepam and intracavernosal papaverine at doses appropriate for age and body weight. These are the only patients who received diazepam. Papaverine is an arteriolar smooth muscle relaxant and causes vasodilatation of the arterioles supplying the corpora. Secondary veno-occlusion develops as intracavernosal pressure rises and the trabecular venules are compressed. Diazepam also has muscle relaxant properties. We believe that our 2 patients had an exacerbated response to papaverine because of summation of these muscle relaxant effects. This finding has not been reported previously, and suggests that caution should be exercised in the choice of papaverine dose in patients receiving an anxiolytic either regularly or as a single dose. If a papaverine-induced erection becomes prolonged, it is best treated by aspiration through a large-bore needle. Should this fail, the intracavernosal injection of an alpha-adrenoceptor agonist such as phenylephrine (I mg bolus) or noradrenaline is usually successful.3 The local application of ice-packs, as used in the first case, is unlikely to be of benefit.
anxiety.
Departments of Urology and Radiology, St Bartholomew’s and Middlesex Hospitals, London EC1A 7BE, UK
J. A. VALE R. S. KIRBY W. LEES
1. Michal V, Kramar R, Pospichal J, Hejhal L. Arterial epigastrico-cavernous anastomosis for the treatment of sexual impotence. World J Surg 1977; 1: 515-20 2. Lue TF, McAninch JW. Priapism. In: Tanagho EA, Lue TF, McClure RD, eds. Contemporary management of impotence and infertility. Baltimore: Williams and
Wilkins, 1988: 201-10. 3. Lue TF, Hellstrom WJG, McAninch JW, Tanagho EA. Priapism: a refined approach to diagnosis and treatment. J Urol 1986; 136: 104-08.
Acute heart
retransplantation
SIR,—The Eurotransplant group (May 11, p 1158) discuss the a "high urgency programme" for acute heart retransplantation. They question whether acute retransplantation is justified but suggest further data and longer follow-up before conclusions can be made. In our opinion the data available demonstrate that urgent retransplantation is unjustifiable. The concept of urgency is a relative one. From March, 1979, to September, 1990, 588 patients were accepted at Papworth Hospital for cardiac transplantation. Although we do not have an urgent category, 136 patients (23%) died before the operation could be done, and the time to death averaged only 66 days. Survival after urgent transplantation is worse than for patients treated electively.’ We have done thirteen cardiac retransplantations in 12 patients over the same period.2 The first graft had failed because of primary organ failure (1 patient;1 day postoperatively), acute rejection (3 patients; atamedianoflldays [range 9-41days]), coronary occlusive disease (8 patients, nine grafts; 1833 [191-3232] days). 8 patients (67%) died within a year. Only those patients who were formally reassessed for operation and had coronary occlusive disease as the cause of graft failure survived for more than 100 days after the transplant operation. The Registry of the International Society for Heart Transplantation, in a more detailed analysis than the one referred to by the Eurotransplant group,3has recorded an operative mortality of 63% for retransplantations within a month compared with 13% for those done more than 6 months after the first operation. Early graft failure results from conditions, such as primary organ failure, severe rejection, and infection, that result in critically ill patients who have a very poor prognosis. This contrasts with patients on "routine" cardiac transplant waiting lists who have a better chance of using scarce organs effectively, but who also are at high risk of dying. If a poorly selected transplanted patient dies, a suitable recipient may have been denied life-saving treatment. The Eurotransplant data point to a 1-year actuarial survival of only 42% for the 25 patients retransplanted from 60 patients listed for reoperation. This is well below the internationally reported 81 % for first-time transplant patients.3 Those data do not include the indications for reoperation or survival figures for patients listed but results of
lymphocytic inflammatory cell infiltration, and neuronal loss with gliosis. White matter was widely affected in 1 patient. Inclusion bodies were not present and electronmicroscopy did not show viral particles. With standard immunohistochemical techniques and mouse monoclonal anti-CMV (Dako) we could not demonstrate CMV antigen, a result similar to that obtained by Power et al.l Using in-situ hybridisation and a biotinylated CMV-DNA probe (Enzo Biochem, New York) with appropriate positive and negative controls
we
could
not
detect CMV nucleic acid in three
representative sections of brain tissue derived from each of 3 patients (total nine sections).3 The CMV probe was derived from a mixture of two clones of CMV sequences, one cloned into the Bam HI site of pIB176 and the other cloned into the Bam HI site of pUC18. This negative result is at variance with the widespread CMV positivity that Power et all obtained in 7 of 10 patients. The presence of Epstein-Barr virus (EBV) in RE brain tissue has been reported previously.’ In view of these discordant results it is possible that RE is an aetiologically diverse disorder in which the fairly uniform clinicopathological features represent the terminal stage of expression of various viral brain infections that include CMV, and others yet to be described. In agreement with Power et all about the need to pursue more convincing evidence of CMV causation we now routinely set up viral cultures on all resected RE brain tissue. Finally, there remains the possibility of viral triggering of an autoimmune mechanism of cortical and white matter destruction in which the initiating virus is no longer detectable by any of the above techniques. Such a hypothesis would be in keeping with the previous demonstration of immune complexes in RE brain tissue5 and would help to explain further the initially positive and subsequently negative CMV in-situ hybridisation study in one of Power and colleagues’ patients.
Department of Pathology and Laboratory Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
M. A. FARRELL L. CHENG M. E. CORNFORD W. W. GRODY H. V. VINTERS
C, Poland SD, Blume WT, et al. Cytomegalovirus and Rasmussen’s encephalitis. Lancet 1990; 336: 1282-84. 2. Rasmussen T, Andermann F. Update on the syndrome of "chronic encephalitis" and epilepsy. Cleveland Clin J Med 1989; 56 (suppl 2): S181-84. 3. Vinters HV, Kwok MK, Ho HW, et al. Cytomegalovirus in the nervous system of patients with the acquired immune deficiency syndrome. Brain 1989; 112: 245-68. 4. Walter FG, Renella RR. Epstein-Barr virus in brain and Rasmussen’s encephalitis. 1. Power
Lancet 1989; i: 279-80. 5. Andrews JM, Thompson JA, Pysher TJ, et al. Chronic encephalitis, epilepsy and cerebrovascular immune complex deposits. Ann Neurol 1990; 28: 88-90
Papaverine, benzodiazepines, and prolonged erections SIR,—The application of intracavernosal drugs to the diagnosis and treatment of erectile dysfunction has gained increasing acceptance since the chance finding in 1977 that papaverine injected into the corpus cavernosum could produce an erection.1 Although generally free from systemic side-effects, prolonged erection is an inevitable risk if a patient’s detumescence mechanisms cannot overcome the action of the drug. We have recently seen 2 patients who showed an interesting association between prolonged erections and simultaneous benzodiazepine and papaverine. A 47-year-old man with a history of erectile failure over several years, despite normal early morning erections, had a normal physical examination and hormonal screen. Before an intracavernosal test dose of 60 mg papaverine, 10 mg of diazepam was given intravenously because of patient anxiety. A full erection was achieved but persisted six h after injection. Despite instruction to return for pharmacological reversal, he attended his local accident and emergency centre, where ice-packs were applied until detumescence took place. A 30-year-old man with normal early morning erections in the absence of any other findings of impotence was diagnosed as having psychogenic erectile failure. Papaverine-stimulated colour doppler studies were completed with 60 mg papaverine; before papaverine injection, 5 mg diazepam was given intravenously because of patient
The doppler study showed an excellent arterial response with no evidence of a venous leak, but full erection persisted five h later and intracavernosal noradrenaline was necessary to reduce it. Both patients had prolonged erections after both diazepam and intracavernosal papaverine at doses appropriate for age and body weight. These are the only patients who received diazepam. Papaverine is an arteriolar smooth muscle relaxant and causes vasodilatation of the arterioles supplying the corpora. Secondary veno-occlusion develops as intracavernosal pressure rises and the trabecular venules are compressed. Diazepam also has muscle relaxant properties. We believe that our 2 patients had an exacerbated response to papaverine because of summation of these muscle relaxant effects. This finding has not been reported previously, and suggests that caution should be exercised in the choice of papaverine dose in patients receiving an anxiolytic either regularly or as a single dose. If a papaverine-induced erection becomes prolonged, it is best treated by aspiration through a large-bore needle. Should this fail, the intracavernosal injection of an alpha-adrenoceptor agonist such as phenylephrine (I mg bolus) or noradrenaline is usually successful.3 The local application of ice-packs, as used in the first case, is unlikely to be of benefit.
anxiety.
Departments of Urology and Radiology, St Bartholomew’s and Middlesex Hospitals, London EC1A 7BE, UK
J. A. VALE R. S. KIRBY W. LEES
1. Michal V, Kramar R, Pospichal J, Hejhal L. Arterial epigastrico-cavernous anastomosis for the treatment of sexual impotence. World J Surg 1977; 1: 515-20 2. Lue TF, McAninch JW. Priapism. In: Tanagho EA, Lue TF, McClure RD, eds. Contemporary management of impotence and infertility. Baltimore: Williams and
Wilkins, 1988: 201-10. 3. Lue TF, Hellstrom WJG, McAninch JW, Tanagho EA. Priapism: a refined approach to diagnosis and treatment. J Urol 1986; 136: 104-08.
Acute heart
retransplantation
SIR,—The Eurotransplant group (May 11, p 1158) discuss the a "high urgency programme" for acute heart retransplantation. They question whether acute retransplantation is justified but suggest further data and longer follow-up before conclusions can be made. In our opinion the data available demonstrate that urgent retransplantation is unjustifiable. The concept of urgency is a relative one. From March, 1979, to September, 1990, 588 patients were accepted at Papworth Hospital for cardiac transplantation. Although we do not have an urgent category, 136 patients (23%) died before the operation could be done, and the time to death averaged only 66 days. Survival after urgent transplantation is worse than for patients treated electively.’ We have done thirteen cardiac retransplantations in 12 patients over the same period.2 The first graft had failed because of primary organ failure (1 patient;1 day postoperatively), acute rejection (3 patients; atamedianoflldays [range 9-41days]), coronary occlusive disease (8 patients, nine grafts; 1833 [191-3232] days). 8 patients (67%) died within a year. Only those patients who were formally reassessed for operation and had coronary occlusive disease as the cause of graft failure survived for more than 100 days after the transplant operation. The Registry of the International Society for Heart Transplantation, in a more detailed analysis than the one referred to by the Eurotransplant group,3has recorded an operative mortality of 63% for retransplantations within a month compared with 13% for those done more than 6 months after the first operation. Early graft failure results from conditions, such as primary organ failure, severe rejection, and infection, that result in critically ill patients who have a very poor prognosis. This contrasts with patients on "routine" cardiac transplant waiting lists who have a better chance of using scarce organs effectively, but who also are at high risk of dying. If a poorly selected transplanted patient dies, a suitable recipient may have been denied life-saving treatment. The Eurotransplant data point to a 1-year actuarial survival of only 42% for the 25 patients retransplanted from 60 patients listed for reoperation. This is well below the internationally reported 81 % for first-time transplant patients.3 Those data do not include the indications for reoperation or survival figures for patients listed but results of
