Biomedical subjects

C Mascott

Publications and source records attributed to C Mascott.

6 recordsLinked to original sources

PubMed2005

Intrathecal grafting of porcine chromaffin cells reduces formalin-evoked c-Fos expression in the rat spinal cord.

Chromaffin cells from the adrenal gland secrete a combination of neuroactive compounds including catecholamines, opioid peptides, and growth factors that have strong analgesic effects, especially when administered intrathecally. Preclinical studies of intrathecal implantation with xenogeneic bovine chromaffin cells in rats have provided conflicting data with regard to analgesic effects, and recent concern over risk of prion transmission has precluded their use in human clinical trials. We previously developed a new, safer source of adult adrenal chromaffin cells of porcine origin and demonstrated an in vivo antinociceptive effect in the formalin test, a rodent model of tonic pain. The goal of the present study was to confirm porcine chromaffin cell analgesic effects at the molecular level by evaluating neural activity as reflected by spinal cord c-Fos protein expression. To this end, the expression of c-Fos in response to intraplantar formalin injection was evaluated in animals following intrathecal grafting of 10(6) porcine or bovine chromaffin cells. For the two species, adrenal chromaffin cells significantly reduced the tonic phases of the formalin response. Similarly, c-Fos-like immunoreactive neurons were markedly reduced in the dorsal horns of animals that had received injections of xenogeneic chromaffin cells. This reduction was observed in both the superficial (I-II) and deep (V-VI) lamina of the dorsal horn. The present study demonstrates that both xenogeneic porcine and bovine chromaffin cells transplanted into the spinal subarachnoid space of the rat can suppress formalin-evoked c-Fos expression equally, in parallel with suppression of nociceptive behaviors in the tonic phase of the test. These findings confirm previous reports that adrenal chromaffin cells may produce antinociception by inhibiting activation of nociceptive neurons in the spinal dorsal horn. Taken together these results support the concept that porcine chromaffin cells may offer an alternative xenogeneic cell source for transplants delivering pain-reducing neuroactive substances.

Animals↗

PubMed2004

Intrathecal xenogeneic chromaffin cell grafts reduce nociceptive behavior in a rodent tonic pain model.

Adrenal medullary chromaffin cells synthetize and secrete a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides. Previous reports have shown that implantation of chromaffin cells into the spinal subarachnoid space can reduce both acute and chronic pain in several animal models. We recently demonstrated that human chromaffin cell grafts in the cerebrospinal fluid (CSF) could alleviate intractable cancer pain after failure of systemic opiates. However, wider application of this approach was limited by the limited availability of allogeneic donor material. Alternatively, chromaffin cells from xenogeneic sources such as bovine adrenal medulla were successful in the experimental treatment of pain, but recent concern over risk of prion transmission precluded use of bovine grafts in human clinical trials. The objective of the present study was to investigate the possibility of developing a new xenogeneic porcine source of therapeutic chromaffin cells because this strategy is currently considered the safest for transplantation in man. In the present study, we report the isolation and the characterization of primary porcine chromaffin cells (PCC) compared to bovine cells. We show, for the first time, that these cells grafted in the rat subarachnoid space can attenuate pain-related behaviors as assessed by the formalin test, a model of tonic pain. Moreover, in addition to behavioral studies, immunohistochemical analysis revealed robust survival of chromaffin cells 35 days after transplantation. Taken together, these results support the concept that porcine chromaffin cells may offer an alternative xenogeneic cell source for transplants delivering pain-reducing neuroactive substances.

Adrenal Medulla↗

PubMed2001

Chronic motor cortex stimulation for phantom limb pain: correlations between pain relief and functional imaging studies.

Chronic motor cortex stimulation (CMCS) has provided satisfactory control of pain in patients with central or trigeminal neuropathic pain. We used this technique in 3 patients with intractable phantom limb pain after upper limb amputation. Functional magnetic resonance imaging (fMRI) correlated to anatomical MRI permitted frameless image guidance for electrode placement. Pain control was obtained for all the patients initially and the relief was stable in 2 of the 3 patients at 2 year follow-up. CMCS can be used to relieve phantom limb pain. fMRI data are useful in assisting the neurosurgeon in electrode placement for this indication.

Adult↗

PubMed1990

Cerebrovasculr response to CO2 in edematous brain during either fentanyl or isoflurane anesthesia.

Cerebral blood flow response to changes in PaCO2 was studied in the edematous cerebral cortex of 19 patients with malignant supratentorial tumors using laser Doppler flowmetry technology. General anesthesia for craniotomy was induced with thiopental, 3-5 mg/kg i.v., and N2O, 60% in O2. In random sequence, 8 patients were assigned to receive fentanyl, 6 +/- 1.6 (SEM). mug/kg i.v.; the other 11 received isoflurane, 0.56% end-tidal + 0.07 (SEM). After a craniotomy bone flap was turned and the dura was opened, laser flowmetry probes were placed over surgically undisturbed cortex that was known to be edematous from preoperative CT and MRI scans. Flow index measurements were first made at hypocarbia (PaCO2 = 24.2 +/- 0.9 and 21.5 +/- 2.1 mm Hg for the fentanyl and isoflurane groups, respectively). Minute ventilation was then decreased and cortical flow index was remeasured with PaCO2 = 34.2 +/- 0.6 and 33.0 +/- 0.8 mm Hg for the fentanyl and isoflurane groups, respectively. Hypocarbia during fentanyl-supplemented N2O-O2 anesthesia resulted in a cortical flow index that was 70 +/- 8% of the flow index at near normocarbia (p <0.05). During isoflurane N2O-O2 anesthesia, however, there was a wide variety of responses to hypocarbia, including three patients whose flow indices increased markedly. The mean flow index during hypocarbia was significantly (p <0.05) lower during fentanyl-N2O anesthesia than it was during isoflurane-N2O anesthesia. There was no predictable relationship between the type of brain tumor and the CBF response to hypocapnia during isoflurane-N2O anesthesia. It is concluded that, in edematous brain, cerebral cortical blood flow response to hypocarbia is more likely to be preserved during fentanyl-supplemented N2O-O2 anesthesia than it is during isoflurane-supplemented N2O-O2 anesthesia. In neuropathologic states where hyperventilation is thought to be necessary to reduce cerebral blood flow and decrease brain bulk, isoflurane may be less satisfactory than fentanyl as a supplement to N2O-O2 anesthesia.

Journal Article↗

PubMed1989

Sufentanil, alfentanil, and fentanyl: impact on cerebrospinal fluid pressure in patients with brain tumors.

In order to evaluate the safety of the new synthetic opioids, alfentanil and sufentanil, in neurosurgical patients, we administered sufentanil 1 microg/kg i.v., alfentanil 50 microg/kg i.v. followed by an infusion of 1 microg/kg/min, or fentanyl 5 microg/kg i.v. to 30 patients with supratentorial tumors anesthetized with nitrous oxide (N2O), 60% in O2. Lumbar cerebrospinal fluid pressure (CSFP) and mean arterial pressure (MAP) responses were recorded for 10 min thereafter, while ventilation was held constant [mean PaCO2 = 36.1 +/- 1.0 mm Hg (SEM)]. There was no change in CSFP after fentanyl. In contrast, both sufentanil and alfentanil caused increases in CSFP, equal to 89 +/- 31 % SE (p < 0.05) and 22 +/- 5% (p < 0.05), respectively. MAP decreased after administration of each opioid. Peak decreases in cerebral perfusion pressure (MAP - CSFP) were 14 +/- 3% after fentanyl, 25 +/- 5% after sufentanil, and 37 +/- 3% after alfentanil. It is concluded that because sufentanil increased CSFP in patients who have brain tumors, it also may be contraindicated in other neurosurgical patients at risk for intracranial hypertension. Alfentanil may share this propensity, since CSFP increased despite a profound reduction in MAP. Among the three opioids evaluated, only fentanyl appears to be appropriate for supplementing N2O-2 anesthesia in patients who have compromised intracranial compliance.

Journal Article↗

PubMed1986

Consequences of antenatal diagnosis for pediatric surgery.

Based on an increase from 6000 ultrasound examinations done at the First University Gynecological Hospital of Munich in 1969 to more than 13,000 in 1982, and on an increased rate of antenatally diagnosed malformation, the accuracy of antenatal ultrasound diagnosis was investigated. It turned out that correct diagnosis could be made in over 80% of cases. However, this was incomplete in approximately 40% of the cases, since associated malformations of the gastrico-intestinal tract, congenital heart disease, myelomeningocele in correctly diagnosed hydrocephalus, and others were not recognized. False-positive results were found in 17.5% of cases, false-negative ones in 12.7%. Because of the uncertainty of antenatal diagnosis and ignorance of many physiological parameters, intrauterine surgical treatment cannot be advocated at present. Intrauterine measures are still confined to punctures, administration of drugs, and diagnostic procedures. Further consequences such as termination of pregnancy, psychological aspects, and possible development of intrauterine therapy are discussed.

Abortion, Induced↗