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Biomedical subjects

G Guy

Publications and source records attributed to G Guy.

At least 19 recordsLinked to original sources
PubMed1999

Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma: a pilot study.

BACKGROUND: The authors have developed a new method of drug delivery into the brain using implantable biodegradable microspheres. In this study, this method was used to provide localized and sustained delivery of 5-fluorouracil (5-FU) after the surgical resection of glioblastoma. This antimetabolite and radiosensitizing drug was selected in an attempt to decrease the rate of local recurrence of the tumor. METHODS: Eight patients with newly diagnosed glioblastoma were included in the study and 2 increasing amounts of 5-FU were studied (70 mg and 132 mg). After surgical resection of the tumor, poly(D-L lactide-co-glycolide) 5-FU-loaded microspheres with an average dimension of 45 microm were implanted in the wall of the surgical bed. External beam radiation (59.4 grays) was initiated before the seventh postsurgical day. Patients were followed by clinical examination, magnetic resonance imaging, and 5-FU assays in the blood and cerebrospinal fluid (CSF). RESULTS: 5-FU assays confirmed sustained concentrations in the CSF for at least 1 month. Concentrations of 5-FU in the blood were lower and transitory. Systemic tolerance to the treatment was good; one case of recurrent brain swelling was observed at the higher dose studied. At the time of last follow-up the overall median survival time was 98 weeks from the time of implantation and 2 patients had achieved disease remission at 139 and 153 weeks, respectively. CONCLUSIONS: This study demonstrates that biodegradable microspheres are efficient systems for drug delivery into the brain and may have future application in the treatment of brain tumors. Further studies are needed to confirm the potential of 5-FU-loaded microspheres for the radiosensitization of glioblastoma. [Please see editorial on pages 197-9, this issue].

Adolescent↗
PubMed1999

Corticosterone plasma concentration in male mule ducks: effects of sampling sites, repeated samplings and ACTH injections.

1. Changes in plasma corticosterone concentrations according to puncture sites and various challenges including injections of an ACTH agonist (Immediate Synacthen) were investigated in male mule ducks. 2. Lower concentrations were measured in samples drawn by puncture from the occipital sinus than at a wing vein site. 3. Immobilisation and a single intramuscular injection of saline solution (1 ml, 0.9%) had no effect on plasma corticosterone after 15 min. 4. A single intramuscular injection of ACTH (5 microg/kg body weight) produced a rise (P<0.05) in corticosterone. Maximum concentrations were measured after 10 min and, in the absence of further sampling, a return to initial levels was observed by 1 h. 5. On the other hand, repeated bleedings following ACTH challenge maintained higher corticosterone concentrations. 6. A single intramuscular injection of ACTH at doses ranging between 0.625 to 20 microg/kg body weight increased corticosterone concentrations (P<0.05) in a dose-dependent manner, with the responses plateauing at doses of 1.25 microg/kg and higher.

Adrenocorticotropic Hormone↗
PubMed1999

Differential channelling of liver lipids in relation to susceptibility to hepatic steatosis in the goose.

In response to overfeeding for the production of "foie gras," the Poland goose differs from the Landes goose by a lesser susceptibility to hepatic steatosis, resulting in a lower accumulation of hepatic triacylglycerol (TG), together with a greater exportation of hepatic phospholipid (PL) in very low density lipoproteins (VLDL) and high density lipoproteins (HDL) (Fournier et al., 1997). A study was designed 1) to compare the liver composition in overfed and nonoverfed geese of the two breeds of geese and 2) to determine whether the differential channelling of lipids in response to overfeeding is reflected in the PL and fatty acid profiles of the different hepatic lipids, whether stored or secreted. In nonoverfed geese, there were no breed-related differences in liver weight (approximately 90 to 100 g), hepatic lipid content (3 to 4%), and lipid and PL composition. However, plasma VLDL and HDL of the Landes breed contained a higher phosphatidylcholine (PC) to phosphatidylethanolamine (PE) ratio than those of the Poland breed (20.7 and 33.8 vs 12.6 and 25.6 in VLDL and HDL, respectively). After 14 d of overfeeding, hepatic PL profiles were identical in the two breeds and similar to that in control livers; choline-containing PL accounted for 95% of total PL. In contrast, plasma HDL concentrations of the Landes geese were lower than those of the Poland geese (9.4 vs 12.9 g/L) and their PC:PE (13.6%) and PL-polyunsaturated fatty acids (PUFA) content (25%) were decreased compared with the Poland geese (21.2 and 30%). It is likely that the higher susceptibility to fatty liver of the Landes breed involves a differential channelling of PL, resulting in a greater hepatic retention of PC and PUFA that are necessary for plasma membrane growth and cell hypertrophy.

Animal Feed↗
PubMed1999

[Spontaneous spinal cord herniation: a little-known cause of Brown-Sequard syndrome. Report of two cases and review of the literature].

We report two cases of spinal cord herniation. The first one concerns a 28 year-old female who presented with an eighteen-month past history of spasticity of the right lower limb associated with somesthetic sensorial disturbances of the left side with a T4 level, related to a T3-T4 spinal cord herniation. The second case concerned a 58 year-old female with a past history of a left lower limb pyramidal syndrome associated with somesthetic and proprioceptive sensibilities disturbances of the right side with a T5 level related to a T4-T5 spinal cord herniation. Spinal cord herniation is an uncommon and underestimated cause of a progressive Brown-Sequard syndrome. The diagnosis is now easy on the MRI, showing a ventral attraction of the cord. The outcome is usually good, following the surgical reduction of the herniation.

Adult↗
PubMed1997

Relationships between storage and secretion of hepatic lipids in two breeds of geese with different susceptibility to liver steatosis.

Susceptibility to liver steatosis was studied in Landes and Poland geese, which are hyper- and hyporesponsive, respectively, to overfeeding. Plasma lipoproteins were characterized at different stages of the overfeeding process, whereas fatty liver composition was determined after completion of overfeeding and slaughtering. Before overfeeding, plasma lipoprotein profile was typical of birds in both breeds, except that very low density lipoproteins (VLDL) were low in triglyceride (approximately 30%). Moreover, high-density lipoprotein (HDL) concentration was higher in the Poland geese (6.44 vs 4.97 g/L). During overfeeding, hepatic lipogenesis was increased, and fatty liver resulted from accumulation of primarily triglyceride (approximately 95% of lipid content), but also of all other lipids. This accumulation was significantly greater in the Landes geese for all lipids but phospholipid. Thus, the liver weight was 100% higher in this breed (1,005 g vs 485 g), whereas lipid release during sterilization was twofold higher (26.3 vs 7.5%). Parallel, plasma concentration and triglyceride content of hepatic lipoproteins, VLDL and HDL, increased about one- to twofold, this effect being greater in the Poland geese. Therefore, channeling of triglyceride towards secretion rather than in situ storage may be responsible for the hyporesponsiveness of this breed to overfeeding. In both breeds, and especially in the Landes geese, a relative deficiency in phospholipid synthesis together with an enhanced secretion may be limiting factors of hepatocyte hypertrophia and, therefore, of steatosis.

Animals↗
PubMed1997

[Intradural lumbar disk hernias. Apropos of 6 cases and review of the literature].

Transdural discal hernia is a rare complication of lumbar discal pathology. In this paper, we report five cases of transdural herniated disc and one intraradicular discal hernia. In the literature review, we found 97 cases since the first case described by Walter Dandy in 1942. The main risk in this exceptional location of discal hernia is to miss an intradural discal piece leading to a poor result. MRI or CT scan with intrathecal contrast can show an intradural lesion but they usually fail to indicate its precise nature.

Adult↗
PubMed1996

Hybrid ducks overfed with boiled corn develop an acute hepatic steatosis with decreased choline and polyunsaturated fatty acid level in phospholipids.

Hepatic and plasma lipid changes were investigated in hybrid ducks after steatosis was induced by overfeeding. Fourteen hybrid ducks were force-fed (11 kg corn in 13 days). The liver of the overfed ducks weighed ten times more than that of controls (695 vs 69 g). The phospholipid, ash, water and protein content of the liver were only slightly higher (2.6-, 3.6-, 4.4- and 3.2-fold, respectively) but the liver lipid concentration was 16.5 times higher after than before overfeeding (56.1 vs 3.4 g/100 g liver, respectively). Liver phosphatidylcholine concentration was higher in the control group (32.4 vs 22.9 mol/100 mol phospholipid) revealing a choline deficiency that could contribute to the development of liver steatosis. In liver phospholipid, the level of linoleic and arachidonic acids were markedly decreased in the overfed ducks, from 5 and 18.1 to 3.7 and 7.1 mol/100 mol fatty acids, respectively, and were mainly replaced by oleic acid. Plasma triacylglycerols increased 5.9-fold, cholesterol 2.2-fold and phospholipid 1.6-fold. Heat-induced (50 min at 105 degrees C) fat release, an index of poor liver integrity, was particularly high for the large, fat livers which contained low levels of phospholipids and phosphatidylcholine.

Animal Feed↗
PubMed1996

Effect of stereotactic implantation of biodegradable 5-fluorouracil-loaded microspheres in healthy and C6 glioma-bearing rats.

OBJECTIVE: Poly(lactic acid-co-glycolic acid) (PLAGA) microspheres are promising systems for interstitial chemotherapy of brain tumors. They can be readily implanted by stereotaxy and are biocompatible with the brain, in which they are totally biodegraded within 2 months. 5-Fluorouracil (5-FU) was selected for encapsulation, because this hydrophilic and antimetabolic drug is not directly neurotoxic and does not readily cross the blood-brain barrier. Also, its anticancer activity may be improved by sustained administration. Furthermore, it is a potent radiosensitizer. METHODS: To study their fate and toxicity, two types of 5-FU-loaded PLAGA microspheres were implanted in healthy rats by stereotaxy. One type presented a fast in vitro release profile (FR), and the second exhibited a slow in vitro release pattern (SR) (100% of the encapsulated 5-FU is released within 72 hours and 18 days, respectively). Periodically, rats were killed for microscopic examination. The efficacy of these microspheres on rat glioma was then evaluated. Seven days after stereotactic implantation of C6 malignant glioma cells in the brain, the rats were treated by intratumoral injection of 5-FU solution, blank microspheres, or 5-FU-loaded microspheres (FR and SR types). The mortality of these treated groups was compared by the log-rank test with that of an untreated group. RESULTS: After implantation of two types of 5-FU-loaded PLAGA microspheres, no sign of clinical or histological toxicity was observed. Entrapped 5-FU crystals were observed until Days 12 and 20 postimplantation within FR and SR microspheres, respectively, which suggests a longer releasing period in vivo than in vitro. In the therapeutic evaluation, only intratumoral implantation of SR-type 5-FU-loaded microspheres significantly decreased the mortality (P = 0.017). CONCLUSION: 5-FU-loaded PLAGA microspheres were implanted in rat brains without evident toxicity. Histological examination suggested a longer sustained delivery period in vivo than in vitro. Intratumoral implantation of SR-type 5-FU-loaded microspheres decreased the mortality of C6 tumor-bearing rats. This effect can be related to the local and the sustained delivery of the drug, because 5-FU administered systemically is ineffective against brain tumors.

Animals↗
PubMed1996

Results of surgery for lumbar spinal stenosis in patients aged 80 years or more. A retrospective study of thirty-four cases.

As life expectancy increases and spinal imaging techniques improve, surgery is being increasingly viewed as a therapeutic alternative for symptomatic lumbar spinal stenosis in patients older than 80 years. Thirty-four patients (21 men and 13 women) who had surgery for lumbar spinal stenosis in our department between 1979 and 1994 were studied retrospectively. The most common initial symptoms were walking-related disorders (n = 29) and sciatica or femoral neuralgia (n = 34). All 34 patients underwent laminectomy at one or more levels. Ten patients also had a herniated disk. There were no deaths and only two patients had serious complications (persistent foot drop in one and left-sided hemiplegia in the other). Results were evaluated immediately after surgery and after three and 12 months. The overall result on pain and walking-related disorders was good in 53% of cases, acceptable in 32%, and poor in 15%. Our data suggest that surgery is a reasonable alternative in symptomatic elderly patients who are in good general health. Satisfactory results can be obtained although disabling complications can occur.

Age Factors↗
PubMed1995

[Transpetrosal approaches to the clivus. Surgical anatomy, challenges and limitations].

Radical excision of skull base tumors is a real challenge for neurosurgeons. The need to preserve the nerves and the vessels in the area lead us to use lateral approaches, if the lesion lies lateral to the cavernous portion of the carotid artery and behind the petrous apex. Lateral approaches are classified into two groups: ventrolateral approaches (in front of the cochlea) and dorsolateral approaches (with or without resection of the bony labyrinth). The three surgical approaches studied were the subtemporal preauricular infratemporal, the subtemporal anterior transpetrosal, and the combined supra and infratentorial presigmoid approach. The approaches were performed on adult cadaver heads fixed in formolin. The technique, the exposure, the modifications and extensions, as well as the problems of reconstruction are discussed.

Dissection↗
PubMed1994

Vertebral hemangioma. Spontaneous spinal canal remodeling after fracture.

STUDY DESIGN: The patient in this report had a fracture of a hemangiomatous vertebra with a fragment protruded into the canal and without neurological signs. There was a 12 month follow-up. RESULTS: After conservative treatment, there were no neurologic signs, a good fusion, and natural remodeling of the spinal canal. CONCLUSIONS: The risk of a hemangiomatous vertebra fracture with a fragment retropulsed into the spinal canal and without neurologic signs is low. Also, a remodeling of the spinal canal can occur, as after a burst fracture.

Aged↗
PubMed1994

Genetic parameters from factorial cross breeding in two duck strains (anas platyrhynchos) Brown Tsaiya and Pekin, for growth and fatty liver traits.

1. A total of 655 mule ducklings were produced in three hatches by artificial insemination of common duck females Brown Tsaiya and Pekin "Alienor" and of their 2 reciprocal crossbreds with Muscovy semen. 2. They were fed ad libitum until 6 weeks, then restricted to one meal per day until day 75 and afterwards preforce fed until day 84 and subsequently forced fed by 2 crammers, twice a day, from the age of 85 d and for a maximum of 13 d. 3. Body weight at hatching, 28 d, 56 d, 75 d, 84 d and at slaughter, the number of force-fed meals, the "paletot" weight, the fatty liver weight, the fat release rate after sterilisation of a 60 g portion of liver and the serous melting rate were measured individually. 4. Significant dam genotype and hatch effects were present for all traits. The crammer effect on force feeding traits was also significant. For mule ducks from Brown Tsaiya, Tsaiya x Pekin, Pekin x Tsaiya and Pekin dams respectively, mean body weight was 2356, 3219, 3137 and 3801 g at 12 weeks, "paletot" weight was 1585, 2111, 2110 and 2470 g, fatty liver weight was 441, 585, 563 and 641 g, fat release rate was 35.1, 40.5, 38.2 and 46.0%. 5. The estimated differences between Pekin and Tsaiya genetic effects in their mule progeny were significant and in favour of the Pekin, except for the number of force fed meals and for the serous melting rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Drug targeting into the central nervous system by stereotactic implantation of biodegradable microspheres.

Controlled drug release in the central nervous system through an implantable polymeric vector has been developed in recent years. For this purpose, different polymeric devices composed primarily of synthetic biocompatible and biodegradable polymers have been investigated. The first polymeric devices developed were macroscopic implants (monolithic devices), which required open surgery for implantation. Microencapsulation methods, however, allow the production of microparticles or nanoparticles loaded with neuroactive drugs. Because of their size, these micro- or nanoparticles may be easily implanted by stereotaxy in discrete, precise, and functional areas of the brain without causing damage to the surrounding tissue. Presently, this method is most frequently applied in the fields of neuro-oncology and neurodegenerative diseases, but neurologically, the potential applications of drug targeting by stereotactic implantation of drug-loaded particles are legion.

Biodegradation, Environmental↗
PubMed1994

[Epidural hematoma. Myth and reality, based on 3 exemplary cases].

The acute epidural hematoma is a real surgical emergency with a good outcome if the operation is performed in reasonable delays. In 1994, too many young patients eventually died or were left with major disabilities, because of an unacceptable and almost always avoidable loss of time. We do emphasize some rules which have to be followed to avoid catastrophic events.

Accidents, Traffic↗
PubMed1994

[Malignant astrocytoma of the cerebellum. Apropos of 10 cases. Review of the literature].

While reviewing a series of 138 cerebellar tumors operated upon between 1978 and 1991, the authors could only find 2 glioblastomas and 8 anaplastic astrocytomas, occurring in 4 children (3 to 14 years old) and 6 adults (23 to 48 years old). These 10 cases represent 2% of the all malignant gliomas population observed during the same period of time. Clinically speaking, nothing makes these tumors different from other cerebellar ones. However, with an heterogenous image and an irregular contrast enhancement, the CT (scan) appearance can lead to the diagnosis. 7 lesions develop within the cerebellar vermis (vermis cerebelli) and 3 develop within the cerebellar hemisphere. Total surgical resection is performed in 9 cases and subtotal resection in 1 case (because of the extension to the floor of the fourth ventricle). Adjunctive radiotherapy on their posterior cranial fossa is achieved in 8 cases. The 2 patients with a glioblastoma present with a recurrence of their tumor at 15 months and 6 years respectively, and eventually died. Out of the patients with an anaplastic astrocytoma, 4 are still alive without recurrence and with a median follow-up of 7 years. The pathogenesis of such lesions is discussed. An aggressive therapeutic management is suggested because of the possible prolonged survival rate.

Adolescent↗