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Neurologic Complications in Organ Transplant Recipients
Book reviews
325
limited packaging capabilities of viruses, attention has also turned to chemically-based synthetic cationic liposomes as delivery vehicles. A great many commercial and noncommercial liposome systems are now available. In the neuromuscular ®eld much attention has, quite understandably, concentrated on the possible bene®t of gene therapy in Duchenne muscular dystrophy. Yet this must be the worst model for demonstrating any possible value of gene therapy. The dystrophin gene is enormous and therefore presents major problems in packaging, and all the skeletal muscles, as well as heart muscle, would have to be treated. It might therefore seem more reasonable to test the ef®cacy of any gene therapeutic regime in a disorder where the gene is small, and where the major and most serious phenotypic expression is tissuelimited. For example the STA gene and its function in the cardiac conduction system in Emery±Dreifuss muscular dystrophy. Another experimental approach being considered is the use of synthetic oligonucleotides which may block (antisense) or circumvent a speci®c point mutation. Also, most recently, the possibility of upregulating a protein which could compensate for a genetically de®cient product has attracted attention. For example the upregulation of fetal haemoglobin with hydroxyurea has proved helpful in the management of sickle cell anemia. The possible therapeutic effect of upregulating utrophin to compensate for dystrophin de®ciency in Duchenne muscular dystrophy is now being investigated most notably by colleagues in Oxford. Following an introductory chapter which summarizes what is meant by gene therapy, successive chapters deal with viral and non-viral delivery systems, the applications so far in monogenic disorders (most notably cystic ®brosis), multifactorial disorders (cancer, atherosclerosis, and diabetes) and infectious diseases, the problems of targeting speci®c tissues and ®nally the design, ethical problems, and future of gene therapy. Each chapter is well-referenced, upto-date and easy to read. For those who need an authoritative review of this important subject, this little book can be highly recommended. Alan Emery Department of Neurology, Royal Devon & Exeter Hospital, Exeter, UK
The truly remarkable expansion in organ transplantation has signi®cantly increased this area of consultative work for the neurologists, and this book attempts to provide background information for the neurologist facing a clinical problem in an organ transplant recipient The ®rst few chapters outline the peri-operative facts of relevance to a neurologist and provide a useful review of the various techniques used in the different forms of organ transplantation and the obvious potential sources of problems. The second part of the book systematically reviews the diagnosis and management of the major neurological disorders which may af¯ict organ transplant recipients. Chapters of particular merit include an excellent description of the neurological manifestations of immunosuppressive agents. I found this the most useful chapter, as many of these agents produce neurological syndromes which need to be differentiated from the many other conditions which may af¯ict these patients. Less good is the chapter on disorders of consciousness. The authors quite rightly point out the dif®culties of differentiating the effects of sedative agents from the whole range of metabolic and other problems which may be seen in this clinical setting. This is clearly a dif®cult area and it is all too easy to give an adverse prognosis on the basis of a neurological assessment because of a failure to recognize that the patients condition appears worse than it actually is because of the effects of sedative and other drugs. The chapter makes reference to the measurement of drug levels, but does not emphasize suf®ciently the value of the assessment of re¯ex eye movements in patients in coma as most sedative or anaesthetic drugs selectively depress these and hence their assessment can be useful when doubts about the cause of coma or the depth of coma exist. The ®nal few chapters cover neuromuscular disorders, stroke, tumours and demyelinating disorders and provide useful references to these important topics. Overall, this is a useful book and one that should be available to all those working in major institutions that have transplantation programmes in place. Certainly all neurologists in this sort of situation should read the ®rst few chapters that give the background to the major forms of transplantation.
Neurologic Complications in Organ Transplant Recipients ISBN 0 7506 7066 5
PII: S0960 -8 966(99)00121 -2
PII: S 0960-896 6(99)00120-0
Consultative work has always been a big part of the day to day activities of neurologists and requests to see possibly brain damaged patients in Intensive Care Units and Cardiothoracic Centres is a common occurrence for most of us.
N.E.F. Cartlidge Department of Neurology, Ward 11, Royal Victoria In®rmary, Newcastle upon Tyne, NE1 4LP, UK
325
limited packaging capabilities of viruses, attention has also turned to chemically-based synthetic cationic liposomes as delivery vehicles. A great many commercial and noncommercial liposome systems are now available. In the neuromuscular ®eld much attention has, quite understandably, concentrated on the possible bene®t of gene therapy in Duchenne muscular dystrophy. Yet this must be the worst model for demonstrating any possible value of gene therapy. The dystrophin gene is enormous and therefore presents major problems in packaging, and all the skeletal muscles, as well as heart muscle, would have to be treated. It might therefore seem more reasonable to test the ef®cacy of any gene therapeutic regime in a disorder where the gene is small, and where the major and most serious phenotypic expression is tissuelimited. For example the STA gene and its function in the cardiac conduction system in Emery±Dreifuss muscular dystrophy. Another experimental approach being considered is the use of synthetic oligonucleotides which may block (antisense) or circumvent a speci®c point mutation. Also, most recently, the possibility of upregulating a protein which could compensate for a genetically de®cient product has attracted attention. For example the upregulation of fetal haemoglobin with hydroxyurea has proved helpful in the management of sickle cell anemia. The possible therapeutic effect of upregulating utrophin to compensate for dystrophin de®ciency in Duchenne muscular dystrophy is now being investigated most notably by colleagues in Oxford. Following an introductory chapter which summarizes what is meant by gene therapy, successive chapters deal with viral and non-viral delivery systems, the applications so far in monogenic disorders (most notably cystic ®brosis), multifactorial disorders (cancer, atherosclerosis, and diabetes) and infectious diseases, the problems of targeting speci®c tissues and ®nally the design, ethical problems, and future of gene therapy. Each chapter is well-referenced, upto-date and easy to read. For those who need an authoritative review of this important subject, this little book can be highly recommended. Alan Emery Department of Neurology, Royal Devon & Exeter Hospital, Exeter, UK
The truly remarkable expansion in organ transplantation has signi®cantly increased this area of consultative work for the neurologists, and this book attempts to provide background information for the neurologist facing a clinical problem in an organ transplant recipient The ®rst few chapters outline the peri-operative facts of relevance to a neurologist and provide a useful review of the various techniques used in the different forms of organ transplantation and the obvious potential sources of problems. The second part of the book systematically reviews the diagnosis and management of the major neurological disorders which may af¯ict organ transplant recipients. Chapters of particular merit include an excellent description of the neurological manifestations of immunosuppressive agents. I found this the most useful chapter, as many of these agents produce neurological syndromes which need to be differentiated from the many other conditions which may af¯ict these patients. Less good is the chapter on disorders of consciousness. The authors quite rightly point out the dif®culties of differentiating the effects of sedative agents from the whole range of metabolic and other problems which may be seen in this clinical setting. This is clearly a dif®cult area and it is all too easy to give an adverse prognosis on the basis of a neurological assessment because of a failure to recognize that the patients condition appears worse than it actually is because of the effects of sedative and other drugs. The chapter makes reference to the measurement of drug levels, but does not emphasize suf®ciently the value of the assessment of re¯ex eye movements in patients in coma as most sedative or anaesthetic drugs selectively depress these and hence their assessment can be useful when doubts about the cause of coma or the depth of coma exist. The ®nal few chapters cover neuromuscular disorders, stroke, tumours and demyelinating disorders and provide useful references to these important topics. Overall, this is a useful book and one that should be available to all those working in major institutions that have transplantation programmes in place. Certainly all neurologists in this sort of situation should read the ®rst few chapters that give the background to the major forms of transplantation.
Neurologic Complications in Organ Transplant Recipients ISBN 0 7506 7066 5
PII: S0960 -8 966(99)00121 -2
PII: S 0960-896 6(99)00120-0
Consultative work has always been a big part of the day to day activities of neurologists and requests to see possibly brain damaged patients in Intensive Care Units and Cardiothoracic Centres is a common occurrence for most of us.
N.E.F. Cartlidge Department of Neurology, Ward 11, Royal Victoria In®rmary, Newcastle upon Tyne, NE1 4LP, UK