Methylprednisolone half-life during simultaneous barbiturate treatment and mechanical hyperventilation of neurosurgical patients

1985 ◽  
Vol 62 (2) ◽  
pp. 182-185 ◽  
Author(s):  
Jørgen Gabrielsen ◽  
Asger Bendtsen ◽  
Henrik Eriksen ◽  
Steen Andersen
Keyword(s):  
Enzyme Induction ◽  
Half Life ◽  
Marked Reduction ◽  
Sodium Succinate ◽  
Steroid Treatment ◽  
Blood Samples ◽  
Content Type ◽  
Methylprednisolone Sodium Succinate ◽  
Neurosurgical Patients ◽  
Fine Print

✓ The pharmacokinetics of methylprednisolone sodium succinate (MP) were studied in six neurosurgical patients under intensive treatment with large doses of MP, barbiturates, and mechanical hyperventilation. The study showed a remarkable level of enzyme induction within 24 hours after starting treatment, when the first blood samples were taken. The half-life (t½) for MP during barbiturate and hyperventilation therapy was found to be reduced by a mean 55% (p < 0.01) in relation to the t½ of MP when administered alone. Studies on the day after termination of barbiturate intake indicated a tendency for an increase in the t½ of MP, but it was not significantly different from the pretermination assessment (p > 0.05). On the basis of this study it is not possible to determine if the change in t½ alone is governed by enzyme induction or by a combination of this plus a change in the distribution and clearance of the steroid. The clinical implication of these findings is that patients who are undergoing steroid treatment and at the same time are sedated with barbiturates should have their MP dose increased in order to compensate for the marked reduction of t½ of MP.

Effects of a single large dose of methylprednisolone sodium succinate on experimental posttraumatic spinal cord ischemia

1984 ◽  
Vol 61 (1) ◽  
pp. 124-130 ◽  
Author(s):  
Edward D. Hall ◽  
Daniel L. Wolf ◽  
J. Mark Braughler
Keyword(s):  
Spinal Cord ◽  
Sodium Succinate ◽  
Spinal Cord Ischemia ◽  
Repeated Measurements ◽  
Intravenous Dose ◽  
Lumbar Spinal Cord ◽  
Spinal Cord Blood Flow ◽  
Content Type ◽  
Methylprednisolone Sodium Succinate ◽  
Fine Print

✓ The ability of a single large intravenous dose of methylprednisolone sodium succinate (MPSS: 15, 30, or 60 mg/kg) to modify the evolution of lumbar spinal cord ischemia in cats undergoing a contusion injury of 500 gm-cm is examined. Repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus were made via the hydrogen clearance technique before and for 4 to 5 hours after injury. The mean preinjury SCBF for all animals was 12.29 ± 0.77 ml/100 gm/min. Following injury, SCBF began to decrease progressively in vehicle-treated animals to a level of 7.71 ml/100 gm/min, a fall of 37.3%. In contrast, cats that received a 30-mg/kg intravenous dose of MPSS at 30 minutes after injury maintained SCBF within normal limits (p < 0.05 at 3 and 4 hours after contusion). A 15-mg/kg MPSS dose was less effective at preventing posttraumatic white matter ischemia, and a 60-mg/kg dose was essentially ineffective. It was determined that the 30-mg/kg MPSS dose was optimal for supporting SCBF when the drug was given at 30 minutes after spinal trauma, and a second series of experiments was carried out to examine the ability of this dose, when given at longer latencies, to improve decreased flow. Methylprednisolone given at 1½ hours after injury in four cats produced a slight (12.7%) but transient improvement in SCBF, and when administered at 4½ hours in another three animals was totally ineffective. These results show that MPSS in a 30-mg/kg dose can prevent posttraumatic spinal cord ischemia. However, it would appear that the ability of the steroid to reverse the ischemia once it has developed is limited, and probably lost, within a few hours of onset. This further suggests that the ischemic process is irreversible and underscores the need for early treatment with a large MPSS dose in order to prevent full development of ischemia and to promote neurological recovery.

Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury

1999 ◽  
Vol 91 (2) ◽  
pp. 200-204 ◽  
Author(s):  
Erkan Kaptanoglu ◽  
Hakan H. Caner ◽  
H. Selçuk Sürücü ◽  
Filiz Akbiyik
Keyword(s):  
Spinal Cord ◽  
Lipid Peroxidation ◽  
Spinal Cord Injury ◽  
Sodium Succinate ◽  
Content Type ◽  
Methylprednisolone Sodium Succinate ◽  
Cord Injury ◽  
Group 3 ◽  
Ultrastructural Findings ◽  
Fine Print

Object. The purpose of this study was to investigate the effect of mexiletine on lipid peroxidation and on ultrastructural findings after induced spinal cord injury (SCI). The authors also compared the activity of mexiletine to that of the well-known antioxidant, methylprednisolone sodium succinate (MPSS). Methods. Wistar rats were divided into seven groups, (Groups 1–7). Those in Groups 1 and 2 were control animals that underwent laminectomy only, after which nontraumatized spinal cord samples were obtained immediately (Group 1) and 2 hours postsurgery (Group 2). Spinal cord injury was induced in all other groups, and cord samples were obtained at 2 hours postsurgery. The rats in Group 3 underwent SCI alone; those in Group 4 received 30 mg/kg of MPSS intraperitoneally immediately after trauma was induced; and those in Groups 5, 6, and 7 received 1, 10, and 50 mg/kg of mexiletine, respectively, by intraperitoneal injection immediately after trauma was induced. Compared with the levels in control animals, lipid peroxidation was significantly elevated in rats in Groups 3 and 5, but there were no statistical differences among those in Groups 1, 2, 4, 6 and 7 in this regard. Compared with the findings in rats in Group 3, ultrastructural damage post-SCI was minor in rats in Groups 4 and 5, and there was even less damage evident in rats in Group 7. Conclusions. Analysis of these findings showed that administration of 50 mg/kg mexiletine significantly decreased the level of lipid peroxidation and protected spinal cord ultrastructure following SCI.

Antitumor effects of antiprogesterones on human meningioma cells in vitro and in vivo

1994 ◽  
Vol 80 (3) ◽  
pp. 527-534 ◽  
Author(s):  
Yasuhiro Matsuda ◽  
Keiichi Kawamoto ◽  
Katsuzo Kiya ◽  
Kaoru Kurisu ◽  
Kazuhiko Sugiyama ◽  
...  
Keyword(s):  
Marked Reduction ◽  
Tumor Volume ◽  
Collagen Gel ◽  
Antitumor Effects ◽  
Histological Changes ◽  
Content Type ◽  
The Relationship ◽  
Fine Print

✓ The presence of the progesterone receptor (PR) in meningioma tissue has been confirmed by previous investigations. Studies have shown that the antiprogesterone drug, mifepristone, is a potent agent that inhibits the growth of cultured meningioma cells and reduces the size of meningiomas in experimental animal models and humans. However, these studies have not fully examined the relationship between the antitumor effects of an antiprogesterone agent and the expression of the PR. The present study examined the antitumor effects of mifepristone and a new potent antiprogesterone agent, onapristone; a correlation between the antitumor effects of these antiprogesterones and the presence of PR's in meningiomas in vitro and in vivo was also investigated. Meningioma tissue surgically removed from 13 patients was used in this study. In the in vitro arm of the study, mifepristone and onapristone exhibited cytostatic and cytocidal effects against cultured meningioma cells, regardless of the presence or absence of PR's; however, three PR-negative meningiomas showed no response to any dose of mifepristone and/or onapristone. In the in vivo arm, meningioma cells, embedded in a collagen gel, were implanted into the renal capsules of nude mice. Antiprogesterone treatment resulted in a marked reduction of the tumor volume regardless of the presence or absence of PR's. No histological changes in the meningioma cells suggestive of necrosis or apoptosis were detected in any of the mice treated with antiprogesterones. These findings suggest that mifepristone and onapristone have an antitumor effect against meningioma cells via the PR's and/or another receptor, such as the glucocorticoid receptor.

Systemic candidiasis and endophthalmitis in neurosurgical patients

1976 ◽  
Vol 45 (1) ◽  
pp. 95-97 ◽  
Author(s):  
Arthur R. Cushman ◽  
Gerald Friedman ◽  
John Capsavage
Keyword(s):  
Broad Spectrum ◽  
Opportunistic Infections ◽  
Systemic Candidiasis ◽  
High Susceptibility ◽  
Content Type ◽  
Broad Spectrum Antibiotics ◽  
Neurosurgical Patients ◽  
Fine Print

✓ Three cases of systemic candidiasis in neurosurgical patients are presented. Two of the three patients also had endophthalmitis. All of the cases were treated with broad-spectrum antibiotics and glucocorticoids prior to the appearance of candidiasis. The authors stress the high susceptibility of neurosurgical patients to opportunistic infections of this type.

Analysis of loss of heterozygosity on chromosomes 10q, 11, and 16 in medulloblastomas

2001 ◽  
Vol 94 (5) ◽  
pp. 799-805 ◽  
Author(s):  
Xiao-lu Yin ◽  
Jesse C. Pang ◽  
Yan-hui Liu ◽  
Edith Y. Chong ◽  
Yue Cheng ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Loss Of Heterozygosity ◽  
Tumor Suppressor Genes ◽  
Molecular Genetic ◽  
Genetic Material ◽  
Suppressor Genes ◽  
Blood Samples ◽  
Content Type ◽  
Targeted Deletion ◽  
Fine Print

Object. The loss of genetic material from specific chromosome loci is a common feature in the oncogenesis of tumors and is often indicative of the presence of important tumor suppressor genes at these loci. Recent molecular genetic analyses have demonstrated frequent loss of chromosomes 10q, 11, and 16 in medulloblastomas. The aim of this study was to localize the targeted deletion regions on the three aforementioned chromosomes in medulloblastomas. Methods. Loss of heterozygosity (LOH) was examined on chromosomes 10q, 11, and 16 in a series of 22 primary and two recurrent medulloblastomas by using polymerase chain reaction—based microsatellite analysis. The DNA extracted from the tumors and corresponding normal blood samples were amplified independently in the presence of radioactively labeled microsatellite primers, resolved by denaturing gel electrophoresis and processed for autoradiography. The DNA obtained from control blood samples that displayed allelic heterozygosity at a given microsatellite locus were considered informative. Loss of heterozygosity was inferred when the allelic signal intensity of the tumor sample was reduced by at least 40%, relative to that of the constitutional control. The LOH analysis demonstrated that deletions of chromosomes 10q, 11p, and 16q are recurrent genetic events in the development of medulloblastomas. Three subchromosomal regions of loss have been identified and are localized to the deleted in malignant brain tumors 1 [DMBT1] gene site on chromosomes 10q25, 11p13–11p15.1, and 16q24.1–24.3. Conclusions. These results indicate that DMBT1 is closely associated with the oncogenesis of medulloblastomas and highlight regions of loss on chromosomes 11p and 16q for further fine mapping and cloning of candidate tumor suppressor genes that are important for the genesis of medulloblastoma.

The physiopathology of respiration in neurosurgical patients

1979 ◽  
Vol 50 (6) ◽  
pp. 699-714 ◽  
Author(s):  
Elizabeth A. M. Frost
Keyword(s):  
Spinal Cord Injuries ◽  
Pediatric Neurosurgery ◽  
Blood Gas Analysis ◽  
Gas Analysis ◽  
Regulation Of Respiration ◽  
Content Type ◽  
Neurosurgical Patients ◽  
Cord Injury ◽  
Injured Patients ◽  
Fine Print

✓ Regulation of respiration is summarized as to peripheral and central chemoreceptors, controllers of voluntary and automatic respiration, and stimulators (CO2, O2, and pH). The information that may be obtained from blood-gas analysis is reviewed and basic problems in acid-base imbalance described. Commonly employed respiratory patterns are discussed. Preoperative pulmonary assessment necessary in elective intracranial situations, spinal cord injuries, and pediatric neurosurgery is outlined. Some of the special problems of the patient with multiple trauma, including injury to the central nervous system are reviewed. Central and peripheral factors that cause respiratory difficulty in head-injured patients are tabulated, and an outline is given of diagnosis and therapy. There are many possible causes of intraoperative hypoxia and hypercarbia, and these complications with their prevention or treatment are examined. Criteria for extubation are established. Finally, postoperative pulmonary care in elective, emergency, and cord injury situations is discussed. The key to successful perioperative pulmonary care of the neurosurgical patient requires close cooperation between the neurosurgeon and anesthesiologist.

Sirolimus-eluting stents in the canine cerebral vasculature: a prospective, randomized, blinded assessment of safety and vessel response

2004 ◽  
Vol 100 (4) ◽  
pp. 688-694 ◽  
Author(s):  
Elad I. Levy ◽  
Ricardo A. Hanel ◽  
Jay U. Howington ◽  
Balazs Nemes ◽  
Alan S. Boulos ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Bare Metal Stents ◽  
Metal Stents ◽  
Bare Metal ◽  
Cerebral Vasculature ◽  
Blood Samples ◽  
Content Type ◽  
Stent Stenosis ◽  
Fine Print

Object. Use of the sirolimus-eluting stent has led to a reduction of in-stent stenosis following treatment of coronary atherosclerosis, whereas treatment of intracranial atherosclerosis with bare-metal stents results in excessive restenosis rates of approximately 40%. Neurotoxicity effects and vessel injury are unknown in the cerebral vasculature. To assess the safety profile and vascular effects of sirolimus-coated stents, the authors conducted a prospective comparative study in which drug-eluting and bare-metal stents were implanted in the canine basilar artery (BA). Methods. Sixteen mongrel dogs were randomized (eight animals per group) to receive either bare-metal 1.5 × 8—mm (six-cell) stents or sirolimus-eluting stents of the same dimensions. Interventionists, histopathologists, and histopathology technicians who participated in the study were blinded to the stent characteristics. Stents were implanted in the canine BA. Serial peripheral blood samples were obtained during the 1st week after implantation to determine the time-dependent serum concentration of sirolimus. Follow-up angiographic studies were performed 30 days after stent implantation to assess the effects of stent placement on the BA and brainstem perforating vessels. Explantation of the stent and BA was performed immediately after angiography by using a pressurized formalin fixation procedure. Histological and computer-assisted morphometric analyses of specimens obtained in each animal were performed. Sirolimus could not be detected in peripheral blood samples obtained later than 24 hours posttreatment. On follow-up angiography, all perforating vessels observed on initial angiograms remained patent, and no evidence of parent vessel damage or pseudoaneurysm formation was observed. Explanted vessels and brainstem sections did not demonstrate evidence of histological neurotoxicity, such as gliosis or infarction. No significant differences were found in the time to endothelialization of bare-metal and sirolimus-coated stents. Smooth-muscle cell (SMC) proliferation, the putative agent for restenosis, was lower in animals receiving sirolimus-coated stents (p = 0.003). Additionally, intimal fibrin density was increased in the dogs treated with sirolimus-coated stents (p < 0.0001). Histological evidence of an inflammatory response demonstrated a trend toward a reduced response in the sirolimus group (mean 0.58) compared with the bare-metal group (mean 0.83, p = 0.33). Conclusions. No neurotoxic effects were observed in the intracranial vessel walls or brainstem tissue in which sirolimus-coated stents were implanted. Compared with bare-metal stents, the sirolimus-coated devices did not impair endothelialization and, furthermore, tended to reduce the proliferation of SMCs. These findings indicate that sirolimus-coated devices may inhibit in-stent stenosis. Further studies with longer-term follow up are required to assess the restenosis rates of sirolimus-coated stents implanted in the intracranial vasculature.

Neurosurgical hyponatremia: the role of inappropriate antidiuresis

1971 ◽  
Vol 34 (4) ◽  
pp. 506-514 ◽  
Author(s):  
John L. Fox ◽  
Joel L. Falik ◽  
Robert J. Shalhoub
Keyword(s):  
Differential Diagnosis ◽  
Sodium Concentration ◽  
Fluid Restriction ◽  
Urine Sodium ◽  
Content Type ◽  
Inappropriate Secretion ◽  
Neurosurgical Patients ◽  
Inappropriate Antidiuresis ◽  
Fine Print

✓ Of 80 consecutive neurosurgical patients, 23 exhibited inappropriate secretion of the antidiuretic hormone (ISADH); 11 of these patients required marked fluid restriction. Sodium concentration in the urine characteristically increased as serum values decreased. Only by following the urine sodium concentrations could the differential diagnosis of nutritional hyponatremia and ISADH be made. The role of ISADH in cerebral edema is stressed. The treatment recommended for ISADH is marked fluid restriction, whereas in nutritional hyponatremia, saline replacement is indicated.

Avascular necrosis of bone following short-term dexamethasone therapy for brain edema

1984 ◽  
Vol 61 (5) ◽  
pp. 983-985 ◽  
Author(s):  
Avital Fast ◽  
Malvina Alon ◽  
Shmuel Weiss ◽  
Freddy R. Zer-Aviv
Keyword(s):  
Brain Edema ◽  
Avascular Necrosis ◽  
Joint Destruction ◽  
Steroid Treatment ◽  
Bone Scanning ◽  
Short Term ◽  
Content Type ◽  
Dexamethasone Therapy ◽  
Avascular Necrosis Of Bone ◽  
Fine Print

✓ The authors present a case of avascular necrosis of both femoral and humeral heads which developed after short-term steroid treatment for brain edema. Avascular necrosis of bone may develop after short-term as well as after maintenance steroid therapy. Early diagnosis with bone scanning and management may in some cases prevent joint destruction.

A comparison of the Glasgow Coma Scale and the Reaction Level Scale (RLS85)

1988 ◽  
Vol 69 (5) ◽  
pp. 699-706 ◽  
Author(s):  
Jan-Erik Starmark ◽  
Daniel Stålhammar ◽  
Eddy Holmgren ◽  
Björn Rosander
Keyword(s):  
Interobserver Agreement ◽  
Content Type ◽  
Sum Score ◽  
Neurosurgical Patients ◽  
Reaction Level Scale ◽  
Ranking Order ◽  
Level Scale ◽  
Reaction Level ◽  
Relevant Factors ◽  
Fine Print

✓ The Glasgow Coma Scale (GCS) and the Reaction Level Scale (RLS85) were compared for rating neurosurgical patients in regard to ranking order of deficit severity, interobserver variability, and coverage for relevant factors. Four physicians, four registered nurses, and four assistant nurses performed 72 pairwise ratings on 47 neurosurgical patients. The rank correlation between the GCS sum score and the RLS85 was −0.94, suggesting the same ranking order of severity and indicating that the underlying concepts of somnolence, delirium, and motor responses in coma are evaluated in the same way. By the sign test, the RLS85 was shown to have better interobserver agreement than the GCS sum score and the eye-motor-verbal (EMV) profile. The interobserver grading disagreements in both scales were distributed over the entire range of responsiveness, and for the GCS sum score they were slanted to combined segments 9 to 15. The RLS85 showed full coverage of relevant factors, while 43 (60%) of the 72 test occasions in the GCS sum score and the EMV profiles showed untestable features, most often because of patient intubation. The pseudoscore (that is, the choice of value given to untestable features) affects interobserver agreement as well as the estimated overall patient responsiveness in the GCS sum score. Assessment by the order of applying the scales showed a significant effect on the GCS eye-opening scale (p = 0.01) and the GCS sum score (p = 0.03), indicating a sensitivity to environmental stimuli unrelated to the patient's status. This study demonstrates that basically the same information as that found in the separate eye, motor, and verbal scales of the GCS can be combined directly into the RLS85, which has better interobserver agreement and better coverage than the GCS sum score.

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