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A Kader

Publications and source records attributed to A Kader.

At least 19 recordsLinked to original sources
PubMed2000

Topography of the initial cortical component of the median nerve somatosensory evoked potential. Relationship to central sulcus anatomy.

The initial cortical component of the median nerve somatosensory evoked potential (SSEP), the parietal N20, is generated in the posterior bank of the central sulcus and inverts in polarity across the sulcus. The inversion is used to identify the central sulcus. The precentral P20 is sometimes not identifiable in scalp recordings, and this has been attributed to a dipole orientation that directs the maximum positivity downward, into the brain. The authors mapped cortical SSEPs during resection of an arteriovenous malformation in the left sensorimotor area. Preoperative scalp SSEPs over the right hemisphere were normal with a frontal P20, but those over the left hemisphere had an unusual topography with a frontal N20. Intraoperative cortical surface recordings demonstrated an N20-P20 inversion in the inferior-superior rather than the usual posterior-anterior direction. This was a result of the trajectory of the central sulcus over the surface of the brain. The section containing the hand representation was coursing in an anterior-posterior direction. This anatomic variant is an additional cause of absent frontal P20 in scalp recordings. Variations in central sulcus anatomy may cause unusual SSEP topographies, but two-dimensional SSEP mapping and correlation with the sulcal anatomy can still permit localization of the central sulcus in such cases.

Afferent Pathways↗
PubMed1999

Formulation factors affecting drug release from poly(lactic acid) (PLA) microcapsule tablets.

A sustained-release (SR) formulation of phenobarbital (PB) microcapsule tablet was prepared using low molecular weight (MW) DL- and high MW L-poly(lactic acid) (PLA) polymer. Microencapsulation of PB showed a unimodal size distribution (375 to 550 microns) of the microcapsules with high loading capacity (> 84%). Drug release from the microcapsule was influenced by the polymer ratios and increased with an increase in L-PLA amount. Microcapsules and physical mixtures of PB and the PLA were directly compressed independently to form microcapsule and matrix tablets, respectively. Drug release from the microcapsule tablets was significantly lowered (p < .001) compared to matrix tablets or free microcapsule (free microcapsule > matrices > microcapsule tablets). We also investigated the effect of tablet adjuvants, compression pressures, and microcapsule loading on the tablet performance in terms of friability, hardness, porosity, tensile strength, and the release kinetics of PB. The drug release rate increased with increasing compression pressure in the case of Emcompress or lactose, but not Avicel. The drug release rate was three- to fivefold increased with sodium starch glycolate compared to tablets without a disintegrant. With an increase in microcapsule loading, a decrease in the drug release rate was observed; however, the tablet performance remained satisfactory. The morphology of the microcapsules was monitored microscopically after the dissolution and the disintegration of tablets. The drug release accelerated with compression pressures and microcapsule loading from the tablets due to mechanical destruction of the microcapsule wall, which was more clearly seen after disintegration and dissolution of the tablets. Our data suggest that the PLA microcapsule can be tableted to make a SR product without significantly affecting its release kinetics.

Capsules↗
PubMed1998

Drug targeting using low density lipoprotein (LDL): physicochemical factors affecting drug loading into LDL particles.

Low density lipoprotein (LDL) has been found suitable as a targeting carrier for cytotoxic drugs. However, higher drug loading into LDL particles without disrupting their native integrity remains a major obstacle. The purpose of this study is to investigate the different physicochemical factors that may affect drug loading and to characterize LDL-drug conjugates. Doxorubicin (Dox) and 3', 5'-O-dipalmitoyl-5-iodo-2'-deoxyuridine (dpIUdR) were used as reference cytotoxic drugs. Drugs were loaded into LDL particles using the dry film method with or without surfactants, liposomal and the direct addition method. The effects of incubation temperature, time and stoichiometry of LDL-drug conjugates on drug loading were investigated. The LDL-drug conjugates were evaluated for their stability and characterized by differential scanning calorimetry (DSC), denatured gel (SDS-PAGE), and electron microscopy (EM). We have suitably incorporated 45+/-10 Dox and 150+/-25 dpIUdR molecules/LDL particle. A seven-fold increase in Dox incorporation was achieved with the liposomal preparation compared to the dry film method. A 4- to 6-h incubation at 37 degreesC was suitable to restore the native structure of LDL particles. No apo B fragmentation of LDL particles was noted on denatured gel. DSC studies showed no change in the Tm of the LDL and the LDL-drug conjugates. An increase in particle size of LDL-dpIUdR, not LDL-Dox was observed in EM compared to the native LDL which may be related to higher incorporation of dpIUdR. The results indicate that physicochemical factors significantly affect drug loading efficiency and may need to be considered to optimize drug incorporation into LDL particles.

Chromatography, High Pressure Liquid↗
PubMed1998

In vitro release of theophylline from poly(lactic acid) sustained-release pellets prepared by direct compression.

Poly(L-lactic acid), (L-PLA) pellets containing theophylline as a model drug were prepared with increasing bovine serum albumin (BSA) load of 10, 20, 30, 40, or 50% by direct compression. The drug release from pellets was studied in phosphate buffered saline (PBS, pH 7.4) at 37 degrees C. The annealing effect on theophylline release from pellets was also studied at 20, 30, 60, and 80 degrees C. In all cases, release kinetics followed the Higuchian mechanism with an initial burst effect followed by sustained release of theophylline during the experimental period. Increasing BSA load resulted in a linear increase in Higuchian release rates presumably because of the hydrophilic nature of BSA. Furthermore, BSA did not interact chemically with the polymer matrix and was held physically by the dense polymer matrix. However, drug release decreased with an increase in annealing temperature. Release of theophylline was higher from PLA-BSA combination pellets compared to PLA pellets at temperatures below the glass transition temperature (Tg) of the polymer and lower for temperatures above Tg. The temperature effect on drug release may be attributed to both the reduction of core solubility in the bulk phase and the lowering of diffusibility of the polymeric membrane. No drug-polymer interactions or polymer degradation was observed within the experimental setup when studied by differential scanning calorimetry (DSC), infrared (FTIR) spectroscopy, and gravimetric methods. DSC studies of pellets showed no hints of microstructural changes (crystallinity) of the polymers. In our experiments, theophylline was released primarily by leaching through channels and not by polymer degradation. The release rate was dependent on BSA loading and annealing. It may be concluded that PLA pellets can be fabricated suitably using BSA and annealing to design sustained-release preparations of water-soluble drugs.

Administration, Oral↗
PubMed1998

Effect of physicochemical factors on the release kinetics of hydrophilic drugs from poly(L-lactic acid) (L-PLA) pellets.

Poly(L-lactic acid) (L-PLA) pellets intended for either parenteral or oral use were successfully prepared by a direct compression technique without the use of heat or organic solvents. Salicylic acid and theophylline were chosen as drug candidates. The drug release from pellets was affected by the compression pressure. The Higuchi plots of the drugs showed a t1/2 dependent drug release pattern. The release rates of these drugs from PLA pellets were directly correlated to their solubilities in the dissolution media. At lower pH (< 7), the release of salicylic acid was found to be slower than theophylline; however, at higher pH (> 7), the release of salicylic acid was faster than that of the theophylline. The release rate of salicylic acid was higher at higher pHs, which was related to the increase in solubilities. Pellets were annealed at 20, 40, and 80 degrees C. A lower release rate was observed with increasing temperatures. Above the glass transition temperature (Tg) of the polymer, the release of drugs was significantly decreased. The drug release was independent of the ionic strength of the media for both salicylic acid and theophylline. We showed earlier that no drug-polymer interactions or polymer degradation were observed when studied by differentials scanning calorimetry (DSC) and infrared spectroscopy (IR) (1). The release mechanism was primarily physical diffusion and leaching during the experimental period. We conclude that the release of low molecular weight (MW) drugs from the high MW L-PLA was independent of the pH and the ionic strength of the dissolution media, but was dependent on the polarity of the drug and formulation factors, such as compression pressure and annealing temperature.

Administration, Oral↗
PubMed1998

Paraganglioma of the filum terminale: case report and literature review.

A rare case of a paraganglioma of the filum terminale is reported. The patient presented with headache and papilledema. Magnetic resonance imaging demonstrated enlarged ventricles of the brain and a well-demarcated intradural spine tumor. After resection of the tumor, the papilledema and headaches resolved, and the ventricles returned to normal size. Pathologic examination revealed a paraganglioma of the filum terminale. We present this rare case and review the literature of spinal paragangliomas as well as the association of spinal tumors with hydrocephalus.

Adult↗
PubMed1996

Cerebral hyperemia after arteriovenous malformation resection is related to "breakthrough" complications but not to feeding artery pressure. The Columbia University Arteriovenous Malformation Study Project.

To study the pathophysiology of idiopathic postoperative brain swelling or hemorrhage after arteriovenous malformation resection, termed normal perfusion pressure breakthrough (NPPB), we performed cerebral blood flow (CBF) studies during 152 operations in 143 patients, using the xenon-133 intravenous injection method. In the first part of the study, CBF was intraoperatively measured (isoflurane/N2O anesthesia) during relative hypocapnia in 95 patients before and after resection. The NPPB group had a greater increase (P < 0.0001) in mean +/- standard deviation global CBF (28 +/- 6 to 47 +/- 16 ml/100 g/min, n = 5) than did the non-NPPB group (25 +/- 7 to 29 +/- 10 ml/100 g/min, n = 90); both arteriovenous malformation groups showed greater increase (P < 0.05) than did controls undergoing craniotomy for tumor (23 +/- 6 to 23 +/- 6 ml/100 g/min, n = 22). Ipsilateral and contralateral CBF changes were similar. In a second cohort of patients with arteriovenous malformations, CBF was measured at relative normocapnia and it increased (P < 0.002) from pre- to postresection (40 +/- 13 to 49 +/- 15 ml/100 g/min, n = 57). There were no NPPB patients in this latter cohort. The feeding mean arterial pressure was measured intraoperatively before resection or at the last embolization before surgery (n = 64). The feeding mean arterial pressure (44 +/- 16 mm Hg) was 56% of the systemic arterial pressure (78 +/- 12 mm Hg, P < 0.0001) and was not related to changes in CBF from pre- to postresection. There was an association between increases in global CBF from pre- to postresection and NPPB-type complications, but there was no relationship of these CBF changes to preoperative regional arterial hypotension. These data do not support a uniquely hemodynamic mechanism that explains cerebral hyperemia as a consequence of repressurization in hypotensive vascular beds.

Adult↗
PubMed1996

Recurrent cerebral arteriovenous malformations after negative postoperative angiograms.

Angiography has been considered to be the gold standard to judge the success of treatment for cerebral arteriovenous malformations (AVMs). Patients without residual nidus or early draining veins on postoperative angiograms are considered cured, with the risk of hemorrhage eliminated. A series of five patients with recurrent AVMs after negative postoperative angiography is described. All patients had hemispheric AVMs, presented initially with hemorrhage, and were between 5 and 13 years of age. Recurrence was noted 1 to 9 years later (at 12-16 years of age); after a hemorrhage in three patients, seizures in one, and on follow-up magnetic resonance imaging in one. Four patients underwent angiography that showed recurrence of the AVM at or adjacent to the original site. Three years postsurgery, the fifth patient died from a large intracerebral and intraventricular hemorrhage originating in the previous location of the AVM; however, the patient did not undergo angiography at the time of recurrence. The initial negative angiograms obtained postoperatively in these patients may be explained by postoperative spasm or thrombosis of a small residual malformation. However, in the authors' cumulative experience with 808 patients who have undergone complete surgical removal of AVMs (of whom 667 were older than 18 years of age), no case of recurrent AVM has been observed in an adult. Therefore, actual regrowth of an AVM may occur in children and could be a consequence of their relatively immature cerebral vasculature and may involve active angiogenesis mediated by humoral factors. The present findings argue against the assumption that AVMs are strictly congenital lesions resulting from failure of capillary formation during early embryogenesis. It is concluded that delayed imaging studies should be considered in children at least 1 year after their initial negative postoperative arteriogram to exclude a recurrent AVM.

Adolescent↗
PubMed1996

Expression of vascular endothelial growth factor in pediatric and adult cerebral arteriovenous malformations: an immunocytochemical study.

Children and adults may differ with respect to their cerebral vasculature in both normal and pathological states. The authors have identified four pediatric patients in whom a cerebral arteriovenous malformation (AVM) recurred after surgery for removal of the AVM and in whom a normal postoperative angiogram had been obtained. This phenomenon has not been observed in adults. The propensity to regrow a cerebral AVM may reflect a less mature cerebral vasculature and a disregulated angiogenic process. Recently, attention has focused on vascular endothelial growth factor (VEGF) as a possible general mediator of angiogenesis in development and neoplasia. A retrospective immunocytochemical analysis of VEGF expression in AVM tissue was conducted to test the hypothesis that VEGF expression may be found in association with the regrowth of AVMs. The results demonstrate a high degree of astrocytic VEGF expression in four (100%) of four specimens from the initial operation in the children with recurrent AVMs as compared to one (14%) of seven nonrecurrent AVMs in the pediatric and two (25%) of eight adult specimens. All of the specimens from the first operation of the recurrent group demonstrate a clear association of cellular immunoreactivity to the abnormal blood vessels, a relationship that was not observed in the specimens from the nonrecurrent groups. These observations indicate that a humoral mechanism mediated by VEGF may play a role in AVM recurrence.

Adult↗
PubMed1996

The effects of intracranial arteriovenous malformations on cerebral hemodynamics.

Significantly decreased perfusion pressure is common in vascular territories irrigating neuronal tissue in patients with AVMs. Without an adaptive mechanism, many of these patients would suffer from ischemic symptoms because their perfusion pressure would fall well below the lower limit of the "normal" autoregulation curve. There is evidence that an "adaptive autoregulatory displacement" occurs in these patients which maintains CBF above ischemic levels in spite of sometimes severe arterial hypotension. This "adaptive autoregulatory displacement" may explain why only a minority of patients appear to suffer from ischemic neurologic deficits attributed to "steal." Although CBF may be mildly reduced in hypotensive regions, function is maintained and there is no increase in CBV which would be expected as a result of ischemic arteriolar vasodilatation. The mechanism for the coupled reduction in CBF, CBV, and cerebral metabolic rate in AVM patients remains to be determined, but diaschisis and decreased neuronal mass may play a role. Adaptive changes in autoregulation may also explain, in part, why NPPB is only rarely encountered after AVM resection, despite the presence of significant arterial hypotension in the majority of patients. Chronic arteriolar vasodilation does not usually lead to vasomotor paralysis because most patients maintain a constant CBF in spite of increase in systemic arterial pressure. Our studies revealed bihemispheric changes in CBF after AVM removal which do not correlate with pre-resection arterial hypotension. Therefore, arterial hypotension may be a necessary but not sufficient condition for the development of "steal" and NPPB. Other nonhemodynamic mechanisms such as abnormal sensory and autonomic innervation of the cerebral vasculature may play a role in the pathogenesis of cerebral hyperemia. Finally, AVM hemodynamics appear to play an important role in the etiology of spontaneous ICH. There is accumulating evidence that lesions with severe arterial hypotension (and greatest "buffering effect") are least likely to hemorrhage. This is important in clinical practice because these lesions are usually large, high-flow AVMs, that is, those with the highest risk from treatment. Hemodynamic and anatomic characteristics of the venous drainage as well as interactions of AVM flow dynamics with the coagulation system also appear to play an important role in determining the natural history of what is probably a heterogeneous disease process with distinct prognostic risk groups.

Arteriovenous Fistula↗
PubMed1994

Deliberate mild intraoperative hypothermia for craniotomy.

BACKGROUND: Despite enthusiasm for the use of mild hypothermia during neurosurgical procedures, this therapy has not been evaluated systematically. This study examined the feasibility and safety of deliberate mild hypothermia and rewarming. METHODS: Thirty patients scheduled for craniotomy were assigned to either a normothermic or mildly hypothermic group. Tympanic membrane temperature was monitored at anesthetic induction, throughout the isoflurane-fentanyl-N2O-O2 anesthetic, and for 18 h postoperatively. Normothermic patients were warmed to 36.5-37.0 degrees C after an initial temperature decrease, and hypothermic patients were cooled to 35 degrees C. In the hypothermic group temperatures were allowed to drift to 34.5 degrees C before rewarming was initiated. Water blankets and convective heating devices were used to cool and rewarm. RESULTS: The minimum temperature achieved by the hypothermic group was 34.3 +/- 0.4 degrees C. Cooling occurred at a rate of 1.0 +/- 0.4 degrees C/h. Rewarming took place at a rate of 0.7 +/- 0.6 degrees C/h (range 0.1-1.8) in the hypothermic group. Hypothermia did not delay emergence from anesthesia (20 +/- 15 min) compared with normothermia (15 +/- 15 min, P = .45). Mean temperature upon intensive care unit admission was 35.8 +/- 1.0 degrees C for the hypothermic group and 37.1 +/- 0.5 degrees C for the normothermic group (P < 0.0001). The hypothermic patients had more postoperative shivering. From 8 to 18 h postoperatively the temperatures of the two groups were similar except for a slightly greater temperature in the hypothermic patients at 12 h (37.6 +/- 0.5 vs. 37.3 +/- 0.4 degrees C, P = .029). CONCLUSIONS: Although deliberate mild hypothermia is easily achieved intraoperatively, complete rewarming may be difficult to attain during craniotomy with current methods. In addition to the need for determining whether deliberate mild hypothermia confers cerebral protection in humans, the potential risks of the therapy need to be further characterized.

Aged↗
PubMed1994

Evidence for adaptive autoregulatory displacement in hypotensive cortical territories adjacent to arteriovenous malformations. Columbia University AVM Study Project.

We hypothesized that chronic hypotension in normal vascular territories fed by arteriovenous malformation pedicles may reset the lower limit of autoregulation and allow flow to remain constant over a lower pressure range. We studied the effect of increasing systemic mean arterial pressure (SMAP) with phenylephrine on cerebral blood flow using a novel technique. Fourteen patients undergoing 15 procedures were studied before endovascular embolization of arteriovenous malformations under neuroleptic conscious sedation. Mean pressures were transduced via a 1.5-F intracranial microcatheter, which was passed under fluoroscopic guidance into the target feeding artery. The microcatheter was positioned (unwedged) at a point that was relatively hypotensive to systemic pressure but that irrigated normal cortex on angiography; feeding mean arterial pressure (FMAP) and SMAP were recorded. A bolus of 133Xe in saline was injected into the microcatheter, and washout was recorded for 3 minutes by a scintillation detector placed over the vascular territory of the injected pedicle. SMAP was then increased approximately 25 mm Hg by phenylephrine infusion, a second bolus was given, and washout was recorded. After exclusion of the shunt spike, initial slope was calculated. The SMAP (mean +/- standard error) increased from 65 +/- 3 to 89 +/- 2 mm Hg (P < 0.0001), and FMAP increased from 46 +/- 3 to 63 +/- 3 mm Hg (P < 0.0001); cerebral blood flow did not change (40 +/- 2 to 40 +/- 2 ml/100 g per min, P = 0.9199). Dividing the cases on the basis of the baseline FMAP into a "severe" hypotensive group (FMAP = 38 +/- 2; n = 7) and a "moderate" hypotensive group (FMAP = 54 +/- 3; n = 8), cerebral blood flow did not change in either group during phenylephrine challenge. Chronic hypotension does not necessarily result in "vasomotor paralysis" with loss of the ability to vasoconstrict to acute increases in perfusion pressure. Instead, it appears to displace adaptively the lower limit of autoregulation in affected vascular territories by a shift of the autoregulatory curve to the left, conceptually analogous to the adaptive displacement seen with chronic hypertension and its treatment.

Adolescent↗
PubMed1994

The influence of hemodynamic and anatomic factors on hemorrhage from cerebral arteriovenous malformations.

The physiological and anatomical aberrations that result in hemorrhage from cerebral arteriovenous malformations (AVMs) remain unclear. In an attempt to clarify which conditions may predispose to hemorrhage, we examined clinical and physiological indices on presentation groups of either hemorrhage or nonhemorrhage in a large cohort of patients (n = 449). Variables examined included AVM size, type of venous drainage, transcranial Doppler (TCD) velocities, feeding mean arterial pressure (FMAP), and draining vein pressure. TCD and pressure data were obtained before any treatment. Age (mean +/- standard deviation) at the time of presentation was 33 +/- 13 years and did not differ between groups. Patients with small (< or = 2.5 cm) AVMs presented more frequently with hemorrhage (90%) than did patients with medium (> 2.5 and < or = 5.0 cm; 52%) or large (> 5.0 cm; 50%) AVMs (P = 0.0001). The 48 of 94 AVMs (51%) with deep venous drainage were more likely to have hemorrhage (P = 0.0219) than were those with superficial drainage (24 of 73 [33%]). Deep drainage was a predictor of hemorrhage even in the subgroup of medium and large supratentorial AVMs (P = 0.005). There was no difference in draining vein pressure (n = 18) between groups (21 +/- 10 and 19 +/- 11 mm Hg, respectively; P = 0.7812). FMAP (n = 52) was higher in the hemorrhage than in the nonhemorrhage group (44 +/- 13 versus 34 +/- 10 mm Hg; P = 0.0007) but was only weakly related to the size of the lesion (largest dimension) (y = -0.74x + 40; r = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗