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Danil Hammoudi.MD

Imene Benayache. MD



The Medical news of August 2003:


Monitored Therapy Articles: 25 Aug 03
The articles below have been selected on the basis of your Monitored Therapies.
  Outcome of symptomatic patients undergoing extracardiac Fontan conversion and cryoablation -(J Thorac Cardiovasc Surg)
  Cyclosporin A for the treatment of severe Henoch-Schonlein glomerulonephritis -(Pediatr Nephrol)
  Clinical and cellular pharmacology in relation to solid tumours of childhood -(Cancer Treat Rev)
  Gemcitabine plus cisplatin vs. gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial -(Lung Cancer Online)
  Lung function changes and pulmonary complications in patients with stage III non-small cell lung cancer treated with gemcitabine/cisplatin as part of combined modality treatment -(Lung Cancer Online)
  Phase I/II study of concurrent twice-weekly paclitaxel and weekly cisplatin with radiation therapy for stage III non-small cell lung cancer -(Lung Cancer Online)
  Gemcitabine in cervical cancer -(Gynecol Oncol)
  Gemcitabine combination chemotherapy of ovarian cancer -(Gynecol Oncol)
  Quantitative Analysis of Dobutamine-Atropine Stress Echocardiography -(Eur J Echocardiogr)
  Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography: optimal diagnostic models using off-line tissue Doppler in the MYDISE study -(Eur Heart J)
  Correlation between fine motor activity and striatal dopamine D(2) receptor density in patients with schizophrenia and healthy controls -(Psychiatry Res)
  Antipsychotic treatment in schizophrenia: atypical options and NICE guidance -(Eur Psychiatry)
  Comorbidity of parkinsonism and schizophrenia in a patient treated with clozapine -(Eur Psychiatry)
  Management of Hepatic Arterial Infusion Port Following Prophylactic Regional Chemotherapy in Patients who have Undergone Curative Resection of Colorectal Liver Metastases -(Surg Today)
  Antimicrobial peptides : potential use in skin infections -(Am J Clin Dermatol)
  Efficacy of Intrathecal Morphine for Analgesia Following Elective Cesarean Section: comparison with Previous Delivery -(J Nippon Med Sch)
  Percutaneous treatment of complications occurring during hemodialysis graft recanalization -(Eur J Radiol)
  A patient with rheumatic mitral stenosis and an atrial myxoma -(Eur J Echocardiogr)
more articles
Other Articles of Interest
Help the NTK Initiative be of more value to you and your colleagues.  Please read and rate one or more of these articles.
  Pneumonectomy in children for destroyed lung and the long-term consequences -(J Thorac Cardiovasc Surg)
  A novel method for sentinel lymph node mapping using magnetite in patients with non-small cell lung cancer -(J Thorac Cardiovasc Surg)
  Long-term survival and prognostic factors of five-year survivors with complete resection of non-small cell lung carcinoma -(J Thorac Cardiovasc Surg)
  Reconstruction of the trachea with a tubed radial forearm free flap -(J Thorac Cardiovasc Surg)
  Comparison of polytetrafluoroethylene patch aortoplasty and end-to-end anastomosis for coarctation of the aorta -(J Thorac Cardiovasc Surg)

23 Aug 03 NTK Score Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma -(Cancer)NEW
23 Aug 03 NTK Score Venous Thrombosis in Cancer Patients: Insights from the FRONTLINE Survey -(Oncologist)NEW
23 Aug 03 NTK Score Severe intoxication after an intentional overdose of amlodipine -(Acta Anaesthesiol Scand)NEW
22 Aug 03 NTK Score Linezolid versus vancomycin for treatment of resistant Gram-positive infections in children -(Pediatr Infect Dis J)NEW
22 Aug 03 NTK Score T1a breast carcinoma and the role of axillary dissection -(Arch Surg)NEW
The articles above obtained NTK Scores of 70 or higher using the NTK Science Scoring System.  NTK Scores reflect ratings received through August 24.

These articles are related to your Monitored Therapies and specialty.  For other highly scored articles, click here

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New Definition For Metabolic Syndrome Predicts Coronary Heart Disease And Type 2 Diabetes
A new simplified definition for metabolic syndrome effectively identifies individuals at risk for coronary heart disease (CHD) and type 2 diabetes, report researchers from THE United Kingdom. The definition of metabolic syndrome recently proposed by the National Cholesterol Education Program (NCEP) incorporates thresholds for five easily measured ...Full Story

    Danil Hammoudi.MD

Sinoe Medical Association

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The Bair Hugger Patient Warming System In Prolonged Vascular Surgery: An Infection Risk?

Joseph KC Huang, Elizabeth F Shah, Narayanan Vinodkumar, MA Hegarty, Robert A Greatorex

Crit Care 7(3):R13-R16, 2003. © 2003 BioMed Central, Ltd.

Posted 08/20/2003

Abstract and Introduction


Introduction: Use of the Bair Hugger forced-air patient warming system during prolonged abdominal vascular surgery may lead to increased bacterial contamination of the surgical field by mobilization of the patient's skin flora.
Methods: This possibility was studied by analyzing bacterial content in air and wound specimens collected during surgery in 16 patients undergoing abdominal vascular prosthetic graft insertion procedure, using the Bair Hugger patient warming system. The bacterial colony counts from the beginning and the end of surgery were compared, and the data analyzed using the Wilcoxon matched pairs test.
Results: The results showed not only that there was no increase in bacterial counts at the study sites, but also that there was a decrease (P < 0.01) in air bacterial content around the patient and in the operating theatre after prolonged use of the patient warmer. No wound or graft infections occurred.
Conclusion: The use of this warming system does not lead to increased bacterial contamination of the operating theatre atmosphere, and it is unlikely to affect the surgical field adversely.


Forced-air patient warming systems, such as Bair Hugger (Augustine Medical Inc., Eden Prairie, MN, USA), were developed in the 1980s and are acknowledged as being the most clinically effective patient warming modality.[1,2] The advantages of avoiding hypothermia for patients undergoing major surgical procedures are well established, and include decreased blood loss (with consequent reduction in blood product use),[3] wound infection,[4] duration of intensive care and hospital stay [5,6] and cardiac ischaemia,[7,8] and increased survival.[6,9,10] However, a potential disadvantage is the risk for bacterial contamination of the operating theatre environment. Prolonged exposure of the patient to the exhaust of the warming blanket could potentially mobilize their resident skin organisms into the theatre atmosphere, and thence into the surgical field, possibly increasing the risk for prosthetic material infection. This has not previously been investigated.

We studied whether use of the Bair Hugger patient warming system increased bacterial contamination of the operating theatre and the surgical wound during prolonged surgery.



Sixteen consecutive patients undergoing aortic surgery with prosthetic graft insertion were prospectively studied. All vascular surgery was performed in a standard positive pressure theatre. The Bair Hugger upper body blanket (model 522) was used for all patients. Bacteria sampling sites are shown in Fig. 1. Air samples were taken using standard techniques from the theatre atmosphere (sites A1-A3) and around the axillae (sites B1 and B2), where the exhaust air emerged, using the Biotest RCS centrifugal air sampler and Biotest Hycon TC agar strips (Biotest UK Ltd, Solihull, West Midlands, UK). A total of 160 l of air was sampled in 4 min from each of these sites. Sterile swabs were used to take specimens from the warming unit and hose (site C) and immediately plated onto standard blood agar culture media. Further specimens were taken from the wound edges with touch plates of blood agar (site D). Two readings were taken from each site, one when the warming blanket was first applied at the start of the operation and again at the end of the operation. All the culture media were then incubated at 36°C for 24 hours. The number of bacterial colonies visible to the naked eye on each of the agar strips and culture plates were then counted by hand and recorded.


Figure 1. Sampling sites. A1-A3, room air; B1 and B2, exhaust from under drapes; C, hose and filter of warming unit; D, wound.

The duration of the operation was recorded. There were nine staff circulating in the operating theatre: three surgeons, two anaesthetists, one operating department assistant and three nurses. All patients had three doses of intravenous antibiotics perioperatively. The data were analyzed using the Wilcoxon matched pairs test.[11]



Twelve male and four female patients were included in the present study. Their mean age was 72.5 years (range 60-86 years). The mean duration of use of the warming blanket was 234 min (range 180-270 min). From each site, the number of bacterial colonies at the start of surgery was compared with that at the end of the operation.

Results are shown in Table 1 and Table 2. All operating theatre air specimens (sites A1-A3) exhibited a decrease in colony counts at the end of surgery (mean reduction 36.4%). The exhaust air (sites B1 and B2) colony counts also decreased at the end of surgery, although the size of the reduction was much less (mean reduction 9.5%). In the Wilcoxon matched pairs test, the test statistic T equalled 0, because the rank difference was negative for all specimens from sites A1-A3, and B1 and B2. This indicates that there was a significant decrease in the colony counts at the end of surgery as compared with the beginning (P < 0.01). All filter (site C) and wound specimens (site D) were sterile.

None of the patients developed postoperative wound or prosthetic infections during a 6-month follow-up period.

In the present study bacteria were not typed; only the absolute numbers of colonies cultured were counted. Typing was to be done only if there was an increase in colony counts at the end of surgery, and this did not occur in any of the patients studied.



As indicated above, the benefits of maintaining normothermia in surgical patients is well documented. It has been shown that the warming equipment itself does not cause bacterial dispersal [12] but the role of patient flora was not investigated and the study was not conducted in a true surgical setting. This remained a concern in our unit, especially because some bacteria in wound infections originated from the patients' skin.[13] The present study did not show any increase in the mobilization and dispersal of patient resident skin organisms. The exhaust air from beneath the surgical drapes, which had passed over the patient's skin, showed a decrease in the number of bacterial counts at the end of surgery, and this demonstrated that there was no increase in air contamination associated with the Bair Hugger patient warming system. Furthermore, it indicated that the warm air stream did not force circulation of the patients' skin organisms. If the Bair Hugger were affecting the atmosphere adversely, then the room air counts would also be expected to increase rather than decrease. In fact, the colony numbers in room air and system exhaust were reduced and this was consistent.

Although the study was not designed to evaluate other causes of bacterial presence in the operating theatre, we feel that the higher count at the beginning of surgery in room air may be due to the unrestricted movement of personnel in and out of the operating room, with opening and closing of doors, leading to increased air flow and turbulence. Toward the end of surgery, movement of staff is much less and this may explain the fall in bacterial counts seen as the air turbulence decreases.[14,15]


We conclude that the use of the Bair Hugger patient warming system during prolonged abdominal surgery does not lead to increased bacterial contamination of the operating theatre atmosphere, and it is therefore unlikely to cause contamination of the surgical field.



Table 1. Comparison of the mean number of colonies

Site (see Fig. 1) Mean number of colonies Mean change
Start of operation End of operation
Operating room air (A1-A3) 112.9 (82-296) 71.7 (62-162) 36.4% reduction
Exhaust (B1 and B2) 31.6 (22-90) 28.6 (15-86) 9.5% reduction
Hose/filter (C) 0 0 -
Wound (D) 0 0 -

Values are expressed as mean (range).

Table 2. Comparison of colony numbers

Patient number Number of bacterial colonies at different sites (see Fig. 1)
Room air (A1-A3) Exhaust (B1 and B2)
Pre Post Change Pre Post Change
1 112 71 -41 29 27 -2
2 102 62 -40 32 30 -2
3 99 70 -29 24 22 -2
4 98 73 -25 22 21 -1
5 97 62 -35 27 25 -2
6 120 67 -53 25 23 -2
7 89 63 -26 37 25 -12
8 129 73 -56 24 22 -2
9 124 68 -56 27 23 -4
10 296 141 -155 90 86 -4
11 98 70 -28 30 24 -6
12 82 63 -19 31 30 -1
13 96 66 -30 22 20 -2
14 91 64 -27 28 25 -3
15 90 68 -22 31 29 -2
16 83 66 -17 27 26 -1


  1. Sessler DI: Consequences and treatment of perioperative hypothermia.Anesth Clin North Am 1994, 12:425-456
  2. Mahoney CB, Odom J: Maintaining intraoperative normothermia: a meta-analysis of outcomes with costs.AANA J 1999, 67:155-164
  3. Schmied H, Kurz A, Sessler DI, Kozek S, Reiter A: Mild intraoperative hypothermia increases blood loss and allogenic transfusion requirements during total hip arthroplasty.Lancet 1996, 347:289-292
  4. Leaper DJ, Melling AG: Antibiotic prophylaxis in clean surgery: clean non-implant wounds.J Chemother 2001, 13(spec no 1):96-101
  5. Kurz A, Sessler DI, Lenhardt R: Perioperative normothermia to reduce the incidence of surgical wound infection and shorten hospitalization. Study of Wound Infection and Temperature Group.N Engl J Med 1996, 334:1209-1215
  6. Tryba M, Leban J: Does active warming of severely injured trauma patients influence perioperative morbidity?Anesthesiology 1996, 85(suppl 3A):A283
  7. Frank SM, Fleisher LA, Breslow MJ, Higgins MS, Olson KF, Kelly S, Beattie C: Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. A randomized clinical trial.JAMA 1997, 277:1127-1134
  8. Frank SM, Christopherson R: Unintentional hypothermia is associated with postoperative myocardial ischaemia.Anesthesiology 1993, 78:468-476
  9. Uebelen R, Schultze K: Unintended decreasing body temperature: a stepchild of perioperative care and outcome consequence.Br J Anaesth 1998, 80(suppl 1):A26
  10. Bush Jr H, Hydo LJ, Fisher D: Hypothermia during elective abdominal aortic aneurysm repair: the high price of avoidable morbidity.J Vasc Surg 1995, 21:392-402
  11. Bland M: Introduction to Medical Statistics 3 Edition Oxford: Oxford University Press 2000
  12. Avidan MS, Jones N, Ing R, Khoosal M, Lundgren C, Morrell DF: Convection warmers- not just hot air.Anaesthesia 1997, 52:1073-1076
  13. Bitkover CY, Marcusson E, Ransjo U: Spread of coagulase-negative staphylococci during cardiac operations in a modern operating room.Ann Thorac Surg 2000, 69:1110-1115
  14. Gosden PE, MacGowan AP, Bannister GC: Importance of air quality and related factors in the prevention of infection in orthopaedic implant surgery.J Hosp Infect 1998, 39:173-180
  15. Pittet D, Ducel G: Infectious risk factors related to operating rooms.Infect Control Hosp Epidemiol 1994, 15:456-462

Sidebar: Key Messages

Joseph KC Huang,1 Elizabeth F Shah,1 Narayanan Vinodkumar,1 MA Hegarty,2 and Robert A Greatorex3

1Surgical Registrar, Department of Surgery, Queen Elizabeth Hospital, King's Lynn, UK
2Consultant Pathologist, Department of Microbiology, Queen Elizabeth Hospital, King's Lynn, UK
3Consultant Surgeon, Department of Surgery, Queen Elizabeth Hospital, King's Lynn, UK




Gene Therapy in Parkinson's Disease: A Newsmaker Interview With Matthew During, MD, MSc

Laurie Barclay, MD

Aug. 21, 2003 — Editor's Note: Earlier this week at New York–Presbyterian Hospital, the first of 12 patients approved by the U.S. Food and Drug Administration (FDA) for participation in a phase I trial received gene therapy for severe Parkinson's disease via adeno-associated viral (AAV) vector-mediated somatic cell gene transfer. Under stereotactic guidance, neurosurgeons infused into the subthalamic nucleus (STN) 3.5 billion viral particles, each bearing a copy of a human gene for glutamic acid decarboxylase, an enzyme needed for production of the neurotransmitter gamma aminobutyric acid (GABA).

Opponents of this treatment point to earlier disasters in gene therapy history, suggest that efficacy has not been demonstrated adequately in primates, and express concern that viruses could replicate within the brain or shut down neural transmission by overexpression of inhibitory proteins. Furthermore, therapeutic alternatives such as deep brain stimulation (DBS) have been shown to be effective.

Although the main goal of this phase I trial is safety rather than efficacy, the investigators and their patients are hoping to see some benefit within three months after surgery. To learn more about the implications and expectations of this controversial therapy, Medscape's Laurie Barclay interviewed co-investigator Matthew During, MD, DSc, a professor of molecular medicine at the University of Auckland in New Zealand. Dr. During is founder and consultant of Neurologix, Inc., a company that has an interest in commercialization of gene therapy for neurologic disorders.

Medscape: What does the gene therapy procedure entail?

Dr. During: The surgery entails a stereotactic neurosurgical procedure under local anesthetic. First, magnetic resonance imaging ([MRI] using a new generation 3T machine) is used to image the target region, the subthalamic nucleus (STN). However, because millimeter accuracy is required, during surgery the STN is mapped using microelectrodes by recording from single neurons as the electrode is slowly moved towards the STN using a microdrive. Once the signature firing pattern of the STN is obtained, confirming that the electrode is in the STN, the fine wire electrode is pulled out, leaving just the microelectrode sheath through which a hair-thin (170 µm) hollow vitreous silica fiber is inserted. Thirty-five µL containing 3.5 billion particles of the viral vector, an AAV containing the human GAD gene (cDNA), is then infused at 0.5 µL/min together with 15 µL 25% mannitol. After the 100-minute infusion period, the delivery catheter is withdrawn and the wound closed.

Medscape: Based on animal models and other relevant data, what is the rationale for this procedure?

Dr. During: The rationale is based on both animal experiments as well as proof-of-principle human studies. We know largely from primate studies, but also from human electrophysiological studies, that the STN is overactive in Parkinson's disease, with increased burst and tonic firing of the neurons. This is because the degeneration of midbrain dopaminergic neurons leads to loss of the normal inhibitory drive onto the STN; hence, it is disinhibited or overactive. If you lesion the STN or electrically silence it by using very high frequency electrical stimulation, typically around 130 Hz in DBS, the symptoms of Parkinson's are dramatically reduced. A colleague, Dr. Anders Lozano from the University of Toronto, has published that the effects of DBS can be mimicked by the local infusion of muscimol, a GABA agonist. These data suggest that strategies to inhibit or dampen the firing of the STN should lead to clinical improvement. Because drug infusion lasts only a few minutes and requires a pump and a continuous supply of the drug, it is not a practical procedure.

DBS is effective; however, it is associated with an approximate rate of 30% for adverse events, including infection, erosions, disconnects, battery failures, and pain. This is in addition to the expense: $20,000 for the hardware alone; the need for a second procedure carried out under general anesthesia for implantation of the stimulator in the chest; as well as prolonged and repeated programming time. We believe that if we could obtain similar results to DBS but with a simple one-shot injection approach, with no hardware and under local anesthesia, then this could be a considerable advance and make the 10% to 15% of Parkinson's disease patients who could benefit from surgery more likely to receive an effective therapy.

There is also some theoretical advantage of delivering the GAD gene to the STN over DBS, as the GABA production and release occurs not only in the STN, but in the major afferent pathway in the internal segment of the globus pallidus (GPi), which is also disinhibited in Parkinson's disease. Hence, the gene transfer into the STN leads to inhibition of both the STN and GPi, both of which are targets for DBS. The critical animal experiments in support of this hypothesis were published by our team in Science in October of 2002.

Medscape: How is the first patient doing after surgery?

Dr. During: He is doing great. He was discharged Aug. 20 from New York–Presbyterian Hospital. He has had no fever and no complications. His MRI done two days after surgery shows no inflammation or changes in the STN, just trace evidence of the microelectrode track leading to the STN.

Medscape: What are the expectations for this phase I trial?

Dr. During: First and foremost, safety. In the best-case scenario we would like to see some clinical benefit. This first patient has largely unilateral disease, and we were limited by the FDA for this phase I study to perform unilateral surgery only. The hope is to see clinical benefit even with this lowest dose — the trial includes four patients in each of three dose cohorts, in a traditional open-label, dose-escalation design. We are also monitoring surrogate markers, including 2-deoxyglucose PET, which we believe will be a good barometer of efficient gene transfer.

Medscape: What are the potential advantages and disadvantages of gene therapy compared with DBS and other alternatives?

Dr. During: The major advantages are no hardware; the entire procedure is carried out under local anesthetic; and ultimately we believe this approach will prove safer than alternatives, including DBS. Although we used very precise microelectrode mapping of the STN, in the future we believe that unlike DBS, where placement is absolutely critical down to the millimeter, for gene transfer we could obtain good results even if we were several millimeters from the midtarget zone. Hence, this surgery could be carried out by general neurosurgeons using simple MRI-guided stereotactic procedures. In addition, DBS requires a lot of fiddling and involvement by the referring neurologist, who needs to program the stimulator, and this is not always simple or straightforward. The 30% adverse event rate associated with DBS is also not trivial, and we believe this should be much less with the AAV gene transfer.

The disadvantages of gene therapy largely relate to the unknowns. Nathan Klein is the world's first patient, and therefore we have no evidence of efficacy. It just simply may not work or benefit him and other patients in the future. Secondly, we are using a virus, which can potentially spread or be transported retrogradely by axons projecting to the STN. If that happens, gene expression could occur in regions outside the STN, and this might lead to symptoms similar to those associated with the use of benzodiazepines, drugs that act to facilitate GABA-ergic transmission. Specifically, we might see drowsiness, sedation, and confusion, or potentially other neurologic deficits.

Finally, again because this is such a new approach, there may be untoward effects that are entirely unpredictable. The vector may integrate at low efficiency, and this could disrupt normal gene function, again leading to neurologic signs and symptoms. We have not seen evidence of this in our animal studies, including nonhuman primate safety testing, but the human brain is different and hence there is always the risk of seeing something that was not apparent in the animal studies.

Medscape: Are there other risks associated with gene therapy in general? How do they relate to this specific application?

Dr. During: Several of the most concerning risks associated with gene therapy are less likely with this specific application. The biggest concerns relate to toxicity and immunogenicity of the virus, leading to a major inflammatory response or an overwhelming immune reaction similar to that which occurred with the unfortunate Jesse Gelsinger case. Here, we are using a nonpathogenic virus, which does not elicit significant immune responses, particularly when given directly into the brain, so we do not expect any inflammatory or immunological responses.

The next major concern is whether the vector integrates, and thereby disrupts the expression of normal genes, particularly those involving regulation of the cell cycle. An example of this is the alarming cases of leukemia that occured in two of the children enrolled in the French X-linked SCID protocol, in which high titer retroviruses were used for gene delivery into hemopoietic stem and progenitor cells. This event, we believe, is not a significant risk in our current protocol because first we are not using retroviruses, but AAV. Although AAV can integrate, they do so at a much, much lower frequency, and again, unlike retroviruses, they have never been associated with an oncogenic event.

Moreover, in the target cells in our protocol, postmitotic neurons, activation of oncogenes leads not to the formation of cancer, but to apoptosis of the transduced cells. Hence, even in the worst-case scenario with activation of an oncogene in the target brain region, the cells would die, not form a brain tumor. Ablation of the STN is an experimental therapy of Parkinson's disease and is carried out in places where the costs of DBS are prohibitive, and it shows some efficacy. So this event would likely cause clinical benefit, not harm to the patient.

Medscape: What do you envision as the future role of gene therapy in Parkinson's disease and in other neurodegenerative disorders?

Dr. During: We believe that ultimately gene therapy will replace other surgical approaches, not only to Parkinson's disease but also to epilepsy and potentially to other neurologic disorders. There was much excitement earlier this month about the Science paper on AAV gene therapy of amyotrophic lateral sclerosis, for example. Those investigators also commented that they plan to proceed to clinical trials. We envisage gene therapy being complementary to drug therapy and part of mainstream medicine in the future.

Reviewed by Gary D. Vogin, MD


Laurie Barclay, MD Writer for Medscape Medical News

Medscape Medical News is edited by Deborah Flapan, assistant managing editor of news at Medscape. Send press releases and comments to

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