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Biomedical subjects

P Delaere

Publications and source records attributed to P Delaere.

At least 19 recordsLinked to original sources

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.

Adult↗

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.

Adenocarcinoma, Follicular↗

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.

Deglutition↗

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.

Adenoma↗

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.

Animals↗

Jugular foramen schwannoma: surgical experience in six cases.

PURPOSE: Schwannomas of the lower cranial nerves are rare tumours. We have surgical experience in six patients. MATERIAL AND METHODS: We have retrospectively reviewed the files of the six patients with jugular foramen schwannomas that were treated in multidisciplinary collaboration in the departments of neurosurgery and ENT. RESULTS: From a clinical point of view, the most important finding was that these tumours usually mimic a vestibular schwannoma. The imaging findings however always allowed the differentiation. The surgical technique included in all cases a suboccipital approach for the intracranial part. When large, the extracranial extension had to be removed through a lateral cervical or transfacial approach. There was no mortality and minor morbidity, with good functional outcome. In subtotally removed tumours, recurrence occurred. CONCLUSION: A combined neurosurgical and ENT approach allows for safe removal of these often large skull base tumours.

Adult↗

Viral and non-viral gene therapy partially prevents experimental cisplatin-induced neuropathy.

Sensory neuropathies are a frequent and dose-limiting complication resulting from treatment with cisplatin. Neurotrophin-3 (NT-3) promotes the survival of the large fiber sensory neurones that are impaired in cisplatin-induced neuropathy, and may therefore serve as a preventive agent. However, the short half-life of recombinant NT-3 after systemic administration limits its clinical applications. We compared two muscle-based gene transfer strategies for the continuous delivery of NT-3 to the bloodstream in an experimental model of cisplatin-induced neuropathy. Electrophysiological studies showed that the intramuscular injection of an adenovirus encoding NT-3 partially prevented the cisplatin-induced increase in sensory distal latencies. Similar effects were observed in cisplatin-treated mice that received intramuscular injections of a plasmid encoding NT-3 associated with in vivo electroporation. The two techniques were well tolerated and induced only slight muscle toxicity. Measurement of renal function, weight and survival showed that neither technique increased the toxicity of cisplatin. Our study shows that gene therapy, using either a viral or a non-viral vector, is a promising strategy for the prevention of cisplatin-induced neuropathy.

Adenoviridae↗

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.

Acrylamides↗

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.

Animals↗

Hypoxia and perfusion measurements in human tumors--initial experience with pimonidazole and IUdR.

We describe our preliminary studies on the development of methods to measure hypoxia in standard paraffin sections of human tumors. Three parameters were investigated. First, image analysis of tumor vascularity yielded the parameter diffusion limited fraction (DLF), which is the amount of tumor tissue greater than a fixed distance from the nearest blood vessel. Secondly, the amount of tumor tissue stained with antibodies against bound reduced products of the bioreductive marker pimonidazole was assessed. Finally, the fraction of blood vessels showing no surrounding tumor tissue labeled with lUdR, a cell kinetic marker, was measured. DLF and pimonidazole monitor primarily chronic hypoxia, while it is hypothesized that the IUdR-negative fraction monitors acute hypoxia. Feasibility was demonstrated in a series of 10 esophageal and 10 rectal tumors (no drug administration), 10 cervix tumors (pimonidazole) and 14 head and neck tumors (pimonidazole and lUdR). Significant differences between tumors were found for all parameters. DLF correlated significantly with the pimonidazole fraction when all images of all tumors were included, although mean values per tumor showed no correlation. The IUdR-negative fraction did not correlate with either of the other two parameters. We conclude that it is feasible to measure hypoxia-related, and possibly perfusion-related, parameters on paraffin sections for predictive purposes, although each method needs further validation. Each parameter will be correlated with outcome in a larger study on head and neck tumors treated with surgery with or without postoperative radiotherapy.

Antibodies↗

Pre- and intra-operative findings in primary hyperparathyroidism.

The files were studied of 300 patients operated for primary hyperparathyroidism for the first time. Their median age was 60 years. The female/male ratio was 3/1, but in the younger patients males and females were about equally present. Preoperatively, one third was considered as asymptomatic with respect to hyperparathyroidism. In this subgroup the hypercalcemia was detected coincidentally and the mean parathyroid hormone level was lower than in the others. Another third of the patients had nephrolithiasis, they were on the average younger and there were more males. Finally one third showed other symptoms as gastrointestinal disease, bone disease or general malaise. Intraoperatively, we found a solitary adenoma in 90% of the cases, a double adenoma in 5% (on each side of the neck in half of the cases) and hyperplasia in 4%. The adenomas had a tendency to occur more often in the upper parathyroid glands, but the difference was not important enough to influence the surgical technique. Hyperplasia patients were, on the average, younger and double adenoma patients older. The female/male ratio was 1/1 for hyperplasia and 15/1 for double adenoma.

Adenoma↗

Postoperative course of serum parathyroid hormone and calcium after surgery for primary hyperparathyroidism.

The aim of this study was to describe the course of parathyroid hormone (PTH) and serum calcium after surgery for primary hyperparathyroidism, and to evaluate the usefulness of daily measurement of these parameters. PTH and serum calcium were daily monitored during the early postoperative period in 45 patients where a parathyroid adenoma was removed. PTH showed a sharp drop to a very low level already on the first postoperative day, whereafter a rapid recovery began. Serum calcium decreased more slowly: on the average, the lowest calcium level was seen on the second day. A majority of the patients were temporarily hypocalcemic, apparently to various degrees. After two weeks 38 patients showed a normal calcemia, while six patients remained slightly hypocalcemic. It is concluded that after removal of a parathyroid adenoma an abrupt fall of PTH precedes the decrease of serum calcium. The first day's PTH level is a reliable indicator of the success of the intervention and it should be a major point in the postoperative biochemical follow-up. Repeated measurements of serum calcium are useful, in contrast with the daily dosage of PTH which can be omitted for economical reasons.

Adenoma↗

Parathyroid function in the early postoperative period after thyroidectomy.

Serum levels of parathyroid hormone (PTH) and calcium were studied in 132 patients, divided into three groups: unilateral thyroid-lobectomy, (sub)total thyroidectomy for non-toxic goitre and (sub)total thyroidectomy for hyperthyroidism. It was found that all types of thyroidectomy, even unilateral lobectomy, had a temporary influence on the PTH and calcium metabolism in the early postoperative period, albeit to different degrees. The effect was most pronounced after surgery for hyperthyroidism, which carries the greatest risk for postoperative hypocalcemia. The pathogenesis of transient postoperative hypocalcemia as well as the implications for the surgical management are discussed.

Adult↗

An image-based 3D planning environment for hemicricolaryngectomy and reconstruction by tracheal autotransplantation.

OBJECTIVE: A new conservation method for unilateral glottal cancer with significant subglottal extension consists of a hemicricolaryngectomy and subsequent reconstruction of the laryngeal defect with a transferable patch of revascularized cervical trachea. In order to restore the three crucial functions of the larynx - airway patency, speech, and swallowing--the reconstructed larynx should resemble a situation with one paralyzed and one intact vocal fold at the glottal level. We hypothesize that this result can be achieved when the tracheal patch meets a typical surgical constraint--the so-called paramedian position at the glottal level - and when the patch is rigidly applied. This hypothesis was tested by developing and using an image-based planning system in a number of situations. MATERIALS AND METHODS: An image-based surgery simulator was developed according to the working hypothesis. To validate the transfer from planning towards actual surgery, a cadaver study was set up. Based on a patient case-study, the sufficiency of the hypothesis for obtaining good functional results was evaluated. Finally, post-operative images of patients who were doing well after being operated without pre-operative planning were compared with retrospective planning to check the necessity of the hypothesis in obtaining good functionality of the neolarynx. RESULTS: We were able to design an efficient surgery simulator. The transfer from planning towards actual surgery is accurate, and satisfactory functional results were obtained from the patient case-study. The results from the retrospective planning showed that the hypothesis is not necessary to obtain good functional results, and that the smallest possible resection is preferred from the oncological point of view. CONCLUSION: The working hypothesis is sufficient for good functional results, but is unnecessary and often undesirable from an oncological point of view. Important lessons are drawn concerning our long-term goal of pre-operative determination of the shape and position of a tracheal patch suitable for optimizing the (neo-) laryngeal functions.

Cadaver↗

Weight characteristics of the parathyroid glands in renal hyperparathyroidism.

BACKGROUND: Although the mean weight of normal parathyroid glands is known, reports concerning the weight of hyperplastic glands in renal hyperparathyroidism are rare. The aim was to collect data about the weight of such glands and also to study the intraindividual distribution. METHODS: Statistical results are presented about the weight of 60 parathyroid glands that were removed in 20 patients with renal hyperparathyroidism (the fourth gland was subtotally removed and therefore not included in the study). RESULTS: The median weight was 1.005 g, with a range from 0.10 to 7.15 g. All removed glands were enlarged, but the most salient finding was the wide distribution of weights. Also, the intra-individual variation was great. The largest gland of each patient weighed, on average, three to four times more than the smallest gland of the same subject. CONCLUSION: The weight of the superior glands tended to be somewhat greater in comparison with the inferior glands.

Adult↗

High-level protein secretion into blood circulation after electric pulse-mediated gene transfer into skeletal muscle.

Numerous diseases are linked to the absence or insufficient concentration of a specific plasma protein. Gene transfer is an appealing strategy for correction of such diseases. We report high and sustained plasma secretion of human secreted alkaline phosphatase and of human Factor IX by skeletal muscle of mice. This was obtained by delivering square-wave unipolar electric pulses of low field strength (200 V/cm) and long duration (20 ms) to skeletal muscle previously injected with plasmid DNA encoding for the secreted protein. This intramuscular electrotransfer method allows 30- to 150-fold increase in reporter protein secretion, compared to simple plasmid DNA injection. This increase allows one to obtain values of up to 2200 ng/ml of a reporter circulating protein. Moreover, this high level of secretion remains stable for several months.

Alkaline Phosphatase↗

Efficient DNA electrotransfer into tumors.

DNA transfer to tumor cells of antiproliferative genes or of genes coding for immunomodulatory or antiangiogenic products is a promising approach for cancer therapy. However, intratumoral injection of plasmid DNA either naked or associated to chemical vectors results in a low level of gene expression. Recently, electrically mediated gene transfer has been described to strongly increase foreign gene expression in various tissues. We confirm and extend these observations using long duration electric pulses for several murine and human tumor models, using a reporter gene encoding for luciferase. After plasmid intratumoral injection, eight electric pulses of 20-ms duration were delivered at a frequency of 1 Hz through two flat parallel stainless steel electrodes placed at each side of the tumor. Optimal gene transfer was obtained using a voltage-to-distance ratio comprising between 400 and 600 V/cm. Two days after electrotransfer, we obtained a 10- to 1200-fold increase in gene expression over the naked DNA injection alone, leading to the expression of 0.6 to 300 ng luciferase per tumor. Moreover, histological results using beta-Gal reporter gene injected in H1299 tumor indicate that electrotransfer leads to a substantial increase in the percentage of beta-Gal positive cells. These results confirm the wide potential of electrotransfer for gene therapy in cancer.

Animals↗