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Biomedical subjects

R E George

Publications and source records attributed to R E George.

At least 19 recordsLinked to original sources

Relationship between histopathological features, MYCN amplification, and prognosis: a UKCCSG study. United Kingdom Children Cancer Study Group.

Histological sections from 231 patients with neuroblastoma were reviewed and morphological features and their relationship to age, stage, MYCN amplification (in 128 tumours by Southern analyses), and clinical outcome (based on Shimada risk grouping) determined. Stage 4 disease was associated with poorly differentiated and undifferentiated tumours (P = 0.001), an MKI of >2% (P< 0.001), and Shimada unfavourable histology (UHi) P< 0.0001. In univariate analysis MKI was significant in predicting a poorer relapse-free survival (RFS), low vs. intermediate and high (P< 0.001). Age, MYCN amplification, and Shimada UH also emerged as significant variables. There was a higher proportion of MYCN-amplified tumours with Shimada UH (P = 0.03), and this group had a decreased RFS (P = 0.002). In patients with Shimada FH, MYCN amplification did not significantly predict a poor prognosis. In those with stage 4 disease, Shimada classification was not significant in predicting survival (P = 0.97); the same was true for those over the age of 1 year (P = 0.66). In multivariate analysis, MYCN amplification and Shimada UH both emerged as independent prognostic factors. In conclusion, morphological features assigned some subsets of patients to prognostic risk groups. Most MYCN-amplified tumours have unfavourable histology and a poorer prognosis. However, in patients with stage 4 disease and those over the age of 1 year, other factors that may influence prognosis should be determined.

Age Factors↗

Analysis of candidate gene co-amplification with MYCN in neuroblastoma.

Previous studies have revealed that the MYCN gene spans approximately 7kb, while the amplicon has been estimated to be 100 kb to 1 Mb long [1-3]. This implies that several other genes may be present on the MYCN amplicon. Such co-amplified genes could contribute to the malignant phenotype and might provide an explanation for why not all patients with MYCN amplification have a poor outcome. We investigated 7 neuroblastoma cell lines and 167 primary tumours for the co-amplification of candidate genes known to be present near the MYCN locus: ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box protein gene, DDX1. We also investigated further the pG21 expressed sequence previously reported to be co-amplified with MYCN. No co-amplification with the first 3 genes was found in any of the cell lines or tumour samples. DDX1 was found to be amplified along with MYCN in 4/6 (67%) cell lines and 18/38 (47%) of the MYCN amplified tumours. No amplification of DDX1, ODC1, RRM2 or syndecan-1 was found in the absence of MYCN amplification. DDX1 co-amplification was observed to occur mainly in stage 4 or 4S patients. With the exclusion of those with 4S disease, patients with DDX1 co-amplification had a significantly shorter mean (+/- SE) disease-free interval (4.1 +/- 1.4, n = 8 months) compared with patients with MYCN amplification alone (19.6 +/- 4.5, n = 17) (P = 0.04, Welch's unpaired t-test). The pG21 sequence was identical to part of the DDX1 gene. These observations indicate that there is at least 1 other gene co-amplified with MYCN in a proportion of cases and that those patients with DDX1 co-amplification tend to relapse more quickly. It also implies that the MYCN amplicon is of varied size and/or position relative to the MYCN gene.

Adolescent↗

Investigation of co-amplification of the candidate genes ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box gene, DDX1, with N-myc in neuroblastoma. United Kingdom Children's Cancer Study Group.

Although N-myc amplification is strongly associated with a poor prognosis, not all patients with neuroblastomas having N-myc amplification fare badly. To investigate whether genes other than N-myc are responsible for contributing to the prognosis, we examined seven cell lines and 87 primary tumours for co-amplification of candidate genes known to be present near the normal N-myc locus: ornithine decarboxylase (ODC), ribonucleotide reductase (RRM2), syndecan-1 and a DEAD box protein gene, DDX1. Sequence analysis of the pG21 cDNA clone previously reported to represent an expressed gene frequently co-amplified with N-myc, showed this to be from the DDX1 gene. No co-amplification with the first three genes was found in any of the cell lines or tumour samples. DDX1, however was found to be amplified along with N-myc in 4/6 (67%) cell lines and 6/16 (38%) of the N-myc amplified tumours. Co-amplification of DDX1 and N-myc was found more frequently in stage 4 or 4S tumours than lower stage (1-3) tumours. With the exclusion of a single 4S case, there was a highly significant reduction in the mean disease-free interval from 24.4 +/- 4.7 (SE, n = 10) months for cases with co-amplification of N-myc and DDX1 compared with 9.2 +/- 1.8 (SE, n = 5) months for those cases showing amplification of N-myc alone (P = 0.0056, Welch's unpaired t-test). No amplification of DDX1, ODC, RRM2, or syndecan-1 was found in the absence of N-myc amplification. These observation indicate that the N-myc amplicon is of varied size and/or position relative to the N-myc gene, with DDX1 representing at least one other gene frequently co-amplified with N-myc. Further studies are required to confirm the biological and prognostic significance of DDX1 co-amplification and to elucidate the role that DDX1 plays in tumour genesis and progression.

Base Sequence↗

Cutaneous stigmata of occult spinal dysraphism.

We describe a 4-year-old Hispanic boy with a dermal pit and an overlying macular vascular malformation in the lumbosacral area. Magnetic resonance imaging of the region revealed an intraspinal lesion at L1-L2. A fibrous tract was excised. A benign lipoma intrinsic to the roots of the cauda equina was noted at surgery. The cutaneous stigmata of occult spinal dysraphisms are reviewed.

Child, Preschool↗

Intramuscular picenadol in patients with postoperative pain.

1. The analgesic efficacy and safety of a single 50 mg intramuscular dose of rac-picenadol, a centrally acting agonist-antagonist opioid analgesic, were compared with pethidine (meperidine) 100 mg and placebo in 60 patients with moderate to severe postoperative pain using hourly pain intensity and relief measurements for up to 6 h following injection of the study medications. 2. Both picenadol and pethidine were statistically significantly (P < 0.05) more effective than placebo in reducing pain intensity and in increasing total relief. Patients receiving picenadol and pethidine had higher frequency of somnolence than patients receiving placebo. In addition, patients receiving picenadol 50 mg experienced a higher incidence of confusion (30%), speech disorders (30%), and tremors (25%) than the patients receiving either pethidine or placebo. 3. These results were compared with those of a similar study which investigated the effects of a 25 mg intramuscular dose of picenadol vs pethidine and placebo. This comparison suggests that 25 mg of picenadol is a more acceptable dosage since both 25 and 50 mg were effective dosages.

Adult↗

Clinical experience with a helical bipolar stimulating lead.

Over 100 patients have been treated for partial epilepsy using a NeuroCybernetic Prosthesis System (NCP). The NCP System is comprised of an implantable pulse generator, an implantable bipolar stimulating lead, and an external communication system. The lead delivers electrical impulses from the NCP Generator to the vagus nerve, and includes a connector end that plugs into the generator, a silicone insulated lead body, and the helical electrode array that attaches to the nerve. The surgical implantation technique has a significant impact on lead reliability and performance. The lead electrode has performed well to date. Modifications to further improve reliability have been implemented. Clinical experience, case history examples, and voltage measurements are examined. The lead electrode is an important component of the overall system and plays a significant part in the success of vagus nerve stimulation therapy.

Adolescent↗

Low-grade astrocytoma of the tectal region as an unusual cause of knee pain: case report.

A 12-year-old boy was investigated for knee pain and contractures, and was found to have an intraspinal tumor of a lumbar nerve root and a tumor in the tectal region, both low-grade astrocytomas. We postulated that the tectal region astrocytoma metastasized to the lumbar intraspinal region. After surgery, the child underwent focal irradiation to the posterior fossa supplemented by craniospinal irradiation and a boost dose to the region of the lumbar spinal tumor. A low-grade astrocytoma rarely presents as spinal metastasis. This case may represent the first of a primary tectal low-grade astrocytoma manifesting as a symptomatic spinal mass.

Astrocytoma↗

Anterior sacral meningocele and tuberculous spondylitis of the sacrum in a patient with neurofibromatosis. Case report and review of the literature.

We report a case of an adult male with neurofibromatosis and chronic low back pain. Evaluation revealed an anterior sacral meningocele, pulmonary tuberculosis, and later in the course of his illness, an osteolytic tuberculous mass in the sacrum. The patient was treated medically with a good outcome. The nature of anterior sacral meningoceles and tuberculosis spondylitis, the differential diagnoses, and relevant treatment options are discussed.

Adult↗

Analgesic effect of picenadol, codeine, and placebo in patients with postoperative pain.

A double-blind, parallel study was conducted to evaluate the analgesic effect and safety of a single 25 mg oral dose of picenadol, a centrally acting analgesic, and to compare it with a 60 mg dose of codeine and a placebo in patients with postoperative pain. Two sites using similar protocols enrolled a total of 178 inpatients with postoperative pain. Pain intensity, relief, and adverse experiences were then measured for up to 6 hours after administration of the test medications. Both picenadol and codeine were significantly more effective than placebo in reducing pain intensity (mean sum of pain intensity difference scores: picenadol 5.21, codeine 5.19, and placebo 2.82) and increasing total relief (mean total pain relief: picenadol 10.21, codeine 11.07, and placebo 6.96). Adverse experience profiles were similar among the three treatment groups.

Adult↗

In vitro cytolysis of primitive neuroectodermal tumors of the posterior fossa (medulloblastoma) by lymphokine-activated killer cells.

Short-term stimulation of nonantigen-primed peripheral blood mononuclear leukocytes with interleukin-2 generates a population of oncolytic effectors designated "lymphokine-activated killer" (LAK) cells. These LAK cells express potent lytic activity against a wide spectrum of fresh or cultured autochthonous (patient's own) and allogeneic (unrelated) tumors, yet specifically spare normal tissues. In this study, cells derived from primitive neuroectodermal tumors of the posterior fossa (PNET-PF) were examined for their sensitivity to LAK cytolysis utilizing an in vitro 4-hour chromium-51-release assay. Five early-passage cell lines, derived from primary PNET-PF, demonstrated significant sensitivity to LAK cell cytolysis. Lysis was equally effective in culture medium and cerebrospinal fluid. Three freshly excised PNET-PF exhibited similar susceptibility to lysis by autochthonous LAK cells. Greatly increased expansion of LAK cell cultures could be achieved by short-term stimulation with monoclonal anti-CD3 antibodies in addition to interleukin-2 activation. These findings constitute the preliminary in vitro foundations for potential intrathecal adoptive immunotherapy of PNET-PF with LAK cells.

Adult↗

Characteristics of an MM 22 medical microtron 21 MV photon beam.

Beam quality, surface doses, depths of maximum dose, peak dose rates, beam profiles, and central axis percentage depth doses of a medical microtron's 21 MV photon beam were measured. The half-value layer of lead was 1.35 cm, the half-value layer of water was 23 cm, and the nominal acceleration potential was 17.7 MV. For a 10 X 10 cm2 field at 100 cm SSD, the maximum dose occurred at a depth of 3 g X cm-2 and the surface dose was 18% of the maximum. The highest dose rate at isocenter was approximately 800 cGy X min-1. The worst horns on beam profiles occurred at a depth of 5 cm for the 35 X 35 cm2 field where the dose rate 4 cm from the edge of the beam was 3% higher than that on the central ray. No horns were apparent for fields 25 X 25 cm2 or smaller.

Humans↗

Correlations between laparoscopic and hysteroscopic findings in 497 women with otherwise unexplained infertility.

Laparoscopy and hysteroscopy were undertaken simultaneously in 497 women presenting with otherwise unexplained infertility. Of them, 285 complained of primary infertility and 212 of secondary infertility. Laparoscopic evidence of pelvic inflammatory disease in the absence of endometriosis was noted in 103 patients with primary and in 108 women with secondary infertility. Lesions were noted on hysteroscopy in both groups as well as in 34% of women with normal laparoscopic examinations. No specific dependency could be demonstrated between any laparoscopically detected lesion and hysteroscopically detected lesion. A significant dependency was demonstrated only between a history of secondary infertility and uterine adhesions (chi 2 = 12.03, 1 df, p less than 0.01). While the combined endoscopic findings did not demonstrate any dependency, the findings of this study demonstrate the importance of hysteroscopy in assessing all patients with infertility, especially those with secondary infertility.

Adolescent↗