Microbial Community Dynamics and Response to Plant Growth-Promoting Microorganisms in the Rhizosphere of Four Common Food Crops Cultivated in Hydroponics.

Plant growth promoting microorganisms (PGPMs) of the plant root zone microbiome have received limited attention in hydroponic cultivation systems. In the framework of a project aimed at the development of a biological life support system for manned missions in space, we investigated the effects of PGPMs on four common food crops (durum and bread wheat, potato and soybean) cultivated in recirculating hydroponic systems for a whole life cycle. Each crop was inoculated with a commercial PGPM mixture and the composition of the microbial communities associated with their root rhizosphere, rhizoplane/endosphere and with the recirculating nutrient solution was characterised through 16S- and ITS-targeted Illumina MiSeq sequencing. PGPM addition was shown to induce changes in the composition of these communities, though these changes varied both between crops and over time. Microbial communities of PGPM-treated plants were shown to be more stable over time. Though additional development is required, this study highlights the potential benefits that PGPMs may confer to plants grown in hydroponic systems, particularly when cultivated in extreme environments such as space.

TRACHEAL ALLOTRANSPLANTATION AND REGENERATION.

Non-malignant and malignant obstruction of the tracheal airway causes significant morbidity and mortality. With increased use of artificial airways, benign and iatrogenic complications are increasing. A tracheal stenosis that is less than 5 cm in length can be resected with end-to-end anastomosis. Longer tracheal lesions can be treated in a palliative way by placement of a stent to secure airway lumen patency. The management of tracheal defects is an evolving field. Tracheal transplantation and tracheal regeneration may provide major treatment advances to cases with long-segment tracheal involvement. This review examines the current possibilities and future prospects in the area of tracheal transplantation and regeneration.

Early experience in transoral robotic surgery (TORS) for non-oropharyngeal head and neck malignancies: a review of functional and oncologic outcomes.

OBJECTIVE: To review and summarize functional and oncologic outcomes after transoral robotic surgery (TORS) for non-oropharyngeal head and neck malignancies. DATA SOURCES: The MEDLINE database and bibliographies of relevant studies were searched through December 2014. METHODS: Search strategy was ((transoral) AND surgery) AND robotics) OR TORS. Abstracts and titles were screened for relevance and full articles of the selected records were evaluated and critically appraised after inclusion. Data concerning functional and oncologic outcomes as well as adverse effects were collected. RESULTS: 22 records were eventually included in the review. For TORS in the treatment of glottic, hypopharyngeal ands supraglottic cancer we retained 3 case series (26 patients), 5 case series (36 patients) and 6 case series (67 patients) respectively. 8 case reports/series (14 patients) assessing safety and feasibility of TORS for tumours in the parapharyngeal space, nasopharynx and skull base were also evaluated. In general, treatment of laryngeal and hypopharyngeal cancer by means of TORS seems to be feasible and safe with satisfying functional and short-term oncologic results. For treatment of malignant tumours in the parapharyngeal space, nasopharynx and skull base, the benefits of TORS, when compared to classic surgical techniques, are still uncertain and are particularly based on theoretical advantages. CONCLUSION: TORS offers an interesting new approach for treating non-oropharyngeal head and neck malignancies. However, long-term results are still not reported and TORS should be directly compared to existing therapeutic options in randomized controlled trials. Until then, its use should be subject to critical appraisal.

Superficial circumflex iliac artery perforator flap for reconstruction of oral defects after tumor resection.

BACKGROUND: The superficial circumflex iliac artery perforator (SCIP) flap, which is the most recent advance in free flap surgery, is described as an evolution of the conventional free groin flap. It has been applied to limb and penile reconstruction. The SCIP flap is versatile and has many advantages, but there are few reports on the application of the SCIP flap to head and neck defects. CASE REPORT: We used a SCIP flap for reconstruction after resection of an oral malignant tumor in two women, aged 43 and 55 years, who presented between 2010 and 2012 with squamous cell carcinoma of the right floor of the mouth and tongue. After resection, the SCIP flap was elevated and used to reconstruct the defect Both flaps survived well. CONCLUSIONS: We confirmed that the SCIP flap is an ideal thin, pliable, and reliable skin flap for reconstructing intra-oral soft-tissue defects with minimal donor-site morbidity.

Prefabrication and prelamination strategies for the reconstruction of complex defects of trachea and larynx.

Complex tracheal and laryngeal defects can be reconstructed using prelamination and prefabrication techniques. Three clinical situations are described in detail in the article. In short segment restenosis defects within scarred surroundings, we restore the fibrocartilaginous defect with a radial forearm fascia flap prelaminated with buccal mucosa or cartilage. This provides a newly vascularized inner lining to the tracheal defect and restores the tubular convexity. For long segment defects we need a technique that can withstand respiratory forces. We use a heterotopic prefabrication strategy to vascularize a tracheal allograft wrapped in forearm fascia. Chimerism is created by replacing donor respiratory epithelium with buccal mucosa of the recipient. After orthotopic transfer, this chimerism allows immunosuppression to be tapered and stopped when bronchoscopy shows mucosal integrity of the new trachea, since the recipient epithelium replaces the allogeneic inner tracheal lining by means of a chronic rejection process. A distinct situation occurs after resection of a unilateral larynx tumor, which usually results in a total laryngectomy with loss of both vocal cords, since reconstruction of the hemilarynx is considered too complex. First, we prefabricate a nearby four-ring autologous tracheal segment using radial forearm fascia. In a second stage, this orthotopically vascularized trachea restores the laryngeal structure with the aim to conserve one vocal cord and thus speech. Orthotopic and heterotopic prelamination and prefabrication strategies offer efficient and reproducible solutions for the restoration of challenging short and long segment tracheal defects, as well as unilateral laryngeal defects. The series in this review article are based on previous studies and case reports. The level of evidence is III-"Study of nonconsecutive patients, without a universally applied gold standard: case-control study".

Incidence of multiglandular disease in sporadic primary hyperparathyroidism.

OBJECTIVES: Multiple, minimally invasive surgical techniques have been developed over the last few decades for the management of sporadic primary hyperparathyroidism (PHTP). However, in cases with multiglandular disease, bilateral cervical exploration remains the gold standard. Therefore, it is important to have an accurate estimation of the incidence of multiglandular disease in sporadic PHTP. METHODOLOGY: 698 patients were treated for PHTP between 1993 and 2010 at the University Hospitals Leuven, using the bilateral cervical exploration method. After excluding cases of multiple endocrine carcinoma syndrome, the incidences of double adenoma and multiple gland hyperplasia were investigated in these patients. Age, gender, imaging results, serum calcium and parathyroid hormone concentrations were analyzed and compared to the data of 50 randomly-selected, PHTP patients with solitary adenomas. RESULTS: 6.6% and 2.4% of the patients with sporadic PHTP had double adenomas and multiple gland hyperplasia, respectively. The female/male ratio was 4.8 (38/8) and 1.8 (11/6), and the average age was 63 and 52 yrs for patients with double adenomas and multiple gland hyperplasia, respectively. The patients with solitary adenomas had a female/male ratio of 3.5, and an average age of 60 yrs. There were no significant differences in serum calcium or parathyroid hormone concentrations between patients with multiglandular disease and those with solitary adenomas. CONCLUSIONS: Multiglandular disease occurs in 9% of patients with sporadic PHTP, and cannot be excluded before surgery. This incidence must be considered when using minimally invasive techniques for treatment of sporadic PHTP. In cases of multiglandular disease, bilateral cervical exploration is indicated.

Learning curve in tracheal allotransplantation.

The first vascularized tracheal allotransplantation was performed in 2008. Immunosuppression was stopped after forearm implantation and grafting of the recipient mucosa to the internal site of the transplant. Nine months after forearm implantation, the allograft was transplanted to the tracheal defect on the radial blood vessels. Since then, four additional patients have undergone tracheal allotransplantation, three (patients 2-4) for long-segment stenosis and one (patient 5) for a low-grade chondrosarcoma. Our goal was to reduce the time between forearm implantation and orthotopic transplantation and to determine a protocol for safe withdrawal of immunosuppressive therapy. Following forearm implantation, all transplants became fully revascularized over 2 months. Withdrawal of immunosuppression began 4 months after graft implantation and was completed within 6 weeks in cases 2-4. Repopulation of the mucosal lining by recipient cells, to compensate for the necrosis of the donor mucosa, was not complete. This resulted in partial loss of the allotransplant in patients 2-4. In patient 5, additional measures promoting recipient cell repopulation were made. The trachea may be used as a composite tissue allotransplant after heterotopic revascularization in the forearm. Measures to maximize recipient cell repopulation may be important in maintaining the viability of the transplant after cessation of immunosuppression.

[Successful treatment of subglottic tracheal stenosis with a mucosa-lined radial forearm fascia flap]. / Erfolgreiche Behandlung einer subglottischen Trachealstenose mittels Mukosa-Radialisfaszien-Lappen.

Short-segment tracheal stenosis is often treated by segmental resection and end-to-end anastomosis. Longer-segment stenosis can sometimes be treated using dilation, laser therapy, bronchoscopic stent insertion and segmental resection and reconstruction. Long-segment restenosis with a buildup of scar tissue due to successful resection surgery in the past represents a particular therapeutic challenge and a sufficiently vascularized transplant may be the only option. We describe the case of a 37-year-old patient who underwent a tracheal reconstruction using a mucosa-lined radial forearm flap. Subsequent to a traumatic laryngotracheal fracture, long-term ventilation and multiple surgical interventions, the patient had developed a functionally relevant subglottic stenosis (5.5 cm). Following longitudinal anterior resection of the trachea 1 cm above and below the stenosis, a Dumon® stent was inserted. Simultaneously, a radial forearm fascia flap was harvested, as were two full-thickness buccal mucosa grafts, which were sutured onto the subcutaneous tissue and fascia of the forearm flap. Beginning caudally, the mucosa-lined flap was then sutured, air-tight, into the anterior tracheal defect with the mucosa facing the lumen. Finally, end-to-end anastomosis connected the blood vessels of the radial forearm flap to the recipient blood vessels in the neck. The patient was successfully extubated after 24 h and discharged after 5 days. A postoperative CT scan revealed optimal placement of the stent and the patient's speech and breathing were sufficiently re-established. The stent was removed bronchoscopically 6 weeks after surgery. Examinations during the 6-month follow-up period showed that the diameter of the reconstructed airway was retained and the patient remained symptom-free.

Medullary thyroid cancer: prognostic factors for survival and recurrence, recommendations for the extent of lymph node dissection and for surgical therapy in recurrent disease.

BACKGROUND: We reviewed our experience with MTC (medullary thyroid cancer), focusing on recurrence and survival, recommendations for the extent of lymph node (LN) dissection and surgery for recurrent disease. METHODS: Of 51 MTC patients treated between 1988 and 2008 at the University Hospitals Leuven, 38 previously untreated patients were analysed. RESULTS: Overall and disease-specific (DSS) five-year survival rates were 75% and 82%. Variables univariately associated with DSS were age, pN, stage, vascular invasion, pre-operative recurrent laryngeal nerve function and last calcitonin level. Recurrence occurred in 10 patients (26%). For recurrence, age was no longer a prognostic factor and post-operative calcitonin, number of positive LN and of positive compartments proved to be prognostic factors. Of 21 clinical NO patients, 2 out of 6 (33%) undergoing a prophylactic central neck dissection (ND) based on per-operative palpatory suspicion proved pN+, and 2 out of 9 patients (22%) undergoing a prophylactic lateral ND were pN+. Five patients surgically treated for recurrence did not achieve long-term normalisation of calcitonin, but remained alive with locoregional control. CONCLUSION: Overall survival and DSS rates are within the range reported in the literature. The results confirm that (1) total thyroidectomy and central compartment dissection is the treatment of choice in the cN0 patients, (2) additional ipsilateral lateral ND is needed for cN+ disease in the ipsilateral lateral compartment, and (3) in the clinically uninvolved contralateral lateral neck, per-operative inspection should serve as a basis for a decision about further ND. Locoregional control and prolonged survival is achieved in surgically treated locoregionally recurrent MTC.

[The creation of a vascularized tracheal transplantation]. / La création d'une transplantation trachéale vascularisée.

Reconstruction of long-segment tracheal defects requires a vascularized allograft. We report successful tracheal allotransplantation after indirect revascularization of the graft in a heterotopic position. Immunosuppressive therapy was administered before the operation, and the allograft was wrapped in the recipient's forearm fascia. Once revascularization was achieved, the mucosal lining was replaced progressively with buccal mucosa from the recipient. At four months, the tracheal chimera was fully lined with mucosa, which consisted of respiratory epithelium from the donor and buccal mucosa from the recipient. After withdrawal of immunosuppressive therapy, the tracheal allograft was moved to its correct anatomical position with an intact blood supply. No treatment-limiting adverse effects occurred.

Pre-operative imaging in primary hyperparathyroidism with ultrasonography and sestamibi scintigraphy.

PROBLEM/OBJECTIVE: Resection of pathological parathyroid glands is the only curative therapy in primary hyperparathyroidism. Adequate pre-operative localization of the pathological glands is very useful, whichever surgical technique is preferred. OBJECTIVES: The aim of our study was to evaluate and compare high resolution ultrasonography and sestamibi scintigraphy as pre-operative imaging techniques and to explore their relationship with certain demographic and biochemical variables. PATIENTS AND METHODS: Data from 368 patients with primary hyperparathyroidism referred for surgery were retrospectively analysed. The results of pre-operative imaging were compared with the operative findings and the anatomopathological report. RESULTS: In predicting the correct side of the lesion (right or left), ultrasonography had a positive predictive value (PPV) of 84%, whereas sestamibi imaging had a PPV of 93%. If both imaging techniques had a concordant positive result, the PPV was 99%. The PPV in predicting the correct quadrant, however, was only 61% for sestamibi scintigraphy and 40% for ultrasonography. CONCLUSIONS: In our study, sestamibi imaging was better than ultrasonography as a single pre-operative localization imaging method for primary hyperparathyroidism. A concordant positive result was exceedingly reliable in indicating the side of the lesion. It seemed far more difficult to predict the quadrant correctly, especially because of misinterpretation of the upper adenomas.

Surgical findings and post-operative parathormone levels in patients with secondary hyperparathyroidism.

OBJECTIVE: The peri-operative and immediate post-operative outcome of secondary hyperparathyroidism treated with subtotal parathyroidectomy is reported. METHODS: We studied 100 patients with chronic renal failure who underwent subtotal parathyroidectomy at our department. Surgical eligibility was based on hyperparathyroidism stage, defined by symptoms of osteodystrophy and/or the presence of hypercalcemia and hyperphosphatemia refractory to medical treatment. Parathormone levels were measured pre-operatively and during the first post-operative days. RESULTS: During surgery, four parathyroid glands were identified in 86% of patients, five glands in 1%, and less than four glands in 13%. The ratio of hyperplastic to normal glands was 93:7. No correlation was found between anatomic location of the glands and the presence of hyperplasia. Parathormone decreased to normal or very low values in 93% of the patients. In seven cases, the lowest post-operative parathormone value was above 30 pg/ml, although four glands were removed in four of these patients. In 95% of the patients with four or more identified glands, post-operative serum parathormone levels decreased to normal or very low values. In 23% of the patients with less than four glands, parathormone levels remained too high. On the other hand, post-operative parathormone values normalized in 10 patients who had less than four glands identified during surgery; in two of them, parathyroid tissue was found during postoperative pathological examinations of the resected thyroid lobe. CONCLUSIONS: Subtotal parathyroidectomy is an acceptable treatment in patients with refractory hyperparathyroidism. Our results indicate that there was not a perfect correlation between the number of identified glands and post-operative parathormone in a subset of patients.

Salvage Transoral Laser Microsurgery for Radiorecurrent Laryngeal Cancer: Indications, Limits, and Outcomes.

PURPOSE OF REVIEW: The aim of this report is to identify relevant literature reports on salvage transoral laser microsurgery (TLM); to consider its oncologic and functional outcomes, as well as reported complications; and to address indications and limitations of salvage TLM. FINDINGS: The weighted average of local control after first salvage TLM was 57%. Repeated TLM procedures for second or third recurrences were required in up to 41% of cases, resulting in a weighted average of local control with TLM alone of 67%. The rate of definite laryngeal preservation was 73%. The ultimate local control rate, including cases that required total laryngectomy, was 90%. The overall complication rate after salvage TLM was 14%. SUMMARY: Salvage TLM of radiorecurrent laryngeal cancer yields excellent oncologic outcomes. Serious complications are scarce, hospitalization times are short, and functional outcomes in terms of voice and swallowing are favorable when compared to open conservation laryngeal surgery. The key to success is an optimal patient selection.

Levothyroxine replacement therapy after thyroid surgery.

INTRODUCTION AND AIM: New entities, such as 'subclinical' over- and undersubstitution, are easily diagnosed after thyroid surgery due to improved testing methods, and the incidence of thyroidectomy with lifelong hormone substitution is increasing. Thus, there is a need to review conventional replacement therapy after thyroid surgery. We investigated the adequacy of our thyroid hormone replacement therapy for three months after total-, subtotal-, and hemithyroidectomy using an upper reference limit of thyrotropin (TSH) of 4.6 mU/L. MATERIALS AND METHODS: Eighty-seven patients undergoing thyroidectomy for benign thyroid pathology participated. Levothyroxine (L-T4) treatment began five days after surgery. Preoperatively euthyroid patients received 150 microg L-T4 daily following total thyroidectomy, 100 microg L-T4 after subtotal thyroidectomy, and 50 microg L-T4 after hemithyroidectomy. Preoperatively hyperthyroid patients received 100 microg L-T4 following total thyroidectomy and 50 microg L-T4 following subtotal thyroidectomy. An average of six weeks after surgery, thyrotropin (TSH) was measured (reference limits 0.15-4.60 mU/L), and necessary dose adjustments were made. RESULTS: Of the patients who were preoperatively euthyroid, 45% with total thyroidectomy, 42% with subtotal thyroidectomy, and 17% with hemithyroidectomy required L-T4 dose adjustments. Of the patients who were preoperatively hyperthyroid, 60% of those with total thyroidectomy and all of those with subtotal thyroidectomy required L-T4 dose adjustments. CONCLUSIONS: To avoid over- and undersubstitution after thyroidectomy, an optimal replacement therapy dose is necessary. A small majority of our preoperatively euthyroid patients received adequate therapy. Endocrinological follow-up six weeks after surgery revealed the need for L-T4 dose adjustments, especially in preoperatively hyperthyroid patients. When the extent of resection was similar for hyperthyroid and euthyroid patients, the same initial dose of L-T4 was justified.

Intramuscular plasmid DNA electrotransfer: biodistribution and degradation.

We have studied radiolabelled plasmid DNA biodistribution and degradation in the muscle at different times after injection, with or without electrotransfer using previously defined conditions. Radiolabelled plasmid progressively left the muscle and was degraded as soon as 5 min after plasmid injection, with or without electrotransfer. Autoradiography showed that the major part of injected radioactivity was detected in the interfibrilar space of a large proportion of the muscle. Large zones of accumulation of radioactivity, which seems to be contained in some fibres (more than 20 microm), were identified as soon as 5 min after electrotransfer. Such structures were never observed on slices of non-electrotransferred muscles. However, these structures were not frequent and probably lesional. The surprising fact is that despite the amount of intact plasmid having been greatly reduced between 5 min and 3 h after injection, the level of transfection remains unchanged whether electric pulses were delivered 20 s or 3 h after injection. Such a behavior was similarly observed when injecting 0.3, 3 or 30 microg of plasmid DNA. Moreover, the transfection level was correlated to the amount of plasmid DNA injected. These results suggest that as soon as it is injected, plasmid DNA is proportionally partitioned between at least two compartments. While a major part of plasmid DNA is rapidly cleared and degraded, the electrotransferable pool of plasmid DNA represents a very small part of the amount injected and belongs to another compartment where it is protected from endogenous DNAses.

Swallowing and functional outcome after partial laryngectomy: a literature review.

There is a wide range of partial surgical resections for the treatment of laryngeal tumours. In addition to good cure rates, the main aim is to preserve a competent and functional larynx. Functional outcomes have proven to have a substantial effect on postoperative quality of life and are usually included in clinical studies. This article reviews reported functional outcomes after partial laryngectomies, particularly when related to swallowing. In the majority of patients, reports indicate acceptable feeding without the presence of a permanent tracheostomy. However, a wide variety of methods and variables are used to describe these functional outcomes, making the comparison of functional outcome after different treatment modalities and resections difficult. More objective evaluation procedures are needed for swallowing to reveal the exact pathophysiology, spontaneous progression and prognostic factors after well-defined laryngeal resections.

Brown tumour: presenting symptom of primary hyperparathyroidism.

The skeletal lesions of primary hyperparathyroidism, including brown tumour, are rare nowadays, with the practice of checking serum calcium levels leading to an earlier diagnosis of hyperparathyroidism. Clinical, laboratory, radiographic and histological investigations can lead to a correct diagnosis. Treatment of brown tumour focuses on the hyperparathyroidism, and is usually followed by a regression of the brown tumour. The diagnosis of hyperparathyroidism and brown tumour should be considered in patients with hypercalcaemia and an osteolytic expansive bone lesion. We present a patient where a brown tumour of the mandible was the presenting symptom of primary hyperparathyroidism.

Completion thyroidectomy after the unexpected diagnosis of thyroid cancer.

The optimal surgical management of well-differentiated thyroid cancer (DTC) remains a controversial topic. Preoperative and peroperative investigations quite frequently fail to detect thyroid cancer in cold nodules, and only postoperative histological examination reveals malignancy. In these cases many physicians perform a completion thyroidectomy. Others recommend a conservative approach with close follow-up because of the increased risk of complications after re-operation. In our department, routine management includes completion thyroidectomy once the histopathological report concludes that there is carcinoma, except in cases of papillary carcinoma measuring less than 1 cm. The aim of our study was to determine the incidence of contralateral malignancy and of complications after completion thyroidectomy. We reviewed the records of 29 patients--25 women and 4 men-- who all underwent completion thyroidectomy because of an unexpected diagnosis of DTC. Residual malignancy was found in 12 patients (41.4%) after completion thyroidectomy. In ten patients (34.5%) the malignancy was localised in the contralateral lobe and two patients (6.9%) had lymph node metastases. Postoperative transient hypocalcaemia (< 8.0 mg/dl) occurred in five patients (17.2%) and permanent hypocalcaemia (lasting longer than 6 months) was a feature in two patients. One patient suffered transient laryngeal nerve injury occurred in one patient and there were no permanent lesions. In conclusion, we found residual DTC in 41.4% of patients undergoing reintervention. Because of the rather low re-operation rate, we prefer to perform a completion thyroidectomy to remove potential occult malignancy and to allow for postoperative 131I-treatment in all patients with a diagnosis of malignancy in their thyroid lobectomy specimen, with the exception of papillary carcinoma < 1 cm.

Continuous delivery of neurotrophin 3 by gene therapy has a neuroprotective effect in experimental models of diabetic and acrylamide neuropathies.

Neurotrophic factors (NFs) are promising agents for the treatment of peripheral neuropathies such as diabetic neuropathy. However, the value of treatment with recombinant NF is limited by the short half-lives of these molecules, which reduces efficiency, and by their potential toxicity. We explored the use of intramuscular injection of a recombinant adenovirus encoding NT-3 (AdNT-3) to deliver sustained low doses of NT-3. We assessed its effect in two rat models: streptozotocin (STZ)-induced diabetes, a model of early diabetic neuropathy characterized by demyelination, and acrylamide experimental neuropathy, a model of diffuse axonal neuropathy which, like late-onset human diabetic neuropathy, results in a diffuse sensorimotor neuropathy with dysautonomy. Treatment of STZ-diabetic rats with AdNT-3 partially prevented the slowing of motor and sensory nerve conduction velocities (p < 0.01 and p < 0.0001, respectively). Treatment with AdNT-3 of acrylamide-intoxicated rats prevented the slowing of motor and nerve conduction velocities (p < 0.001 and p < 0.0001, respectively) and the decrease in amplitude of compound muscle potentials (p < 0.0001), an index of denervation. Acrylamide-intoxicated rats treated with NT-3 had higher than control levels of muscle choline acetyltransferase activity (p < 0.05), suggesting greater muscle innervation. In addition, treatment of acrylamide-intoxicated rats with AdNT-3 significantly improved behavioral test results. Treatment with AdNT-3 was well tolerated with minimal muscle inflammation and no detectable general side effects. Therefore, our results suggest that NT-3 delivery by adenovirus-based gene therapy is a promising strategy for the prevention of both early diabetic neuropathy and axonal neuropathies, especially late axonal diabetic neuropathy.

Partial prevention of cisplatin-induced neuropathy by electroporation-mediated nonviral gene transfer.

Cisplatin-induced sensory peripheral neuropathy is the dose-limiting factor for cisplatin chemotherapy. We describe the preventive effect of NT-3 delivery, using direct gene transfer into muscle by in vivo electroporation in a mouse model of cisplatin-induced neuropathy. Cisplatin-induced neuropathy was produced by weekly injections of cisplatin (five injections). Two doses of plasmid DNA encoding murine NT-3 (pCMVNT-3) were tested (5 and 50 microg/animal/injection). Cisplatin-treated mice were given two intramuscular injections. The first injection of pCMVNT-3 was given 2 days before the first injection of cisplatin and the second injection 2 weeks later. Six weeks after the start of the experiment, measurement of NT-3 levels (ELISA) demonstrated significant levels both in muscle and plasma. We observed a smaller cisplatin-related increase in the latency of the sensory nerve action potential of the caudal nerve in pCMVNT-3-treated mice than in controls (p < 0.0001). Mean sensory distal latencies were not different between the 5- and 50- microg/animal/injection groups. Treatment with gene therapy induced only a slight muscle toxicity and no general side effects. Therefore, neurotrophic factor delivery by direct gene transfer into muscle by electroporation is of potential benefit in the prevention of cisplatin-induced neuropathy and of peripheral neuropathies in general.