Percent spinal canal compromise on MRI utilized for predicting the need for surgical treatment in single-level lumbar intervertebral disc herniation

BACKGROUND CONTEXT: There is limited information describing the correlation between the initial quantitative measurements on magnetic resonance imaging (MRI) scans of disc herniation area, canal cross-section areas, percent canal compromise, and disc herniation location to the need for surgery. PURPOSE: Our aim is to determine if the size of disc herniation area, canal cross-section area, percent canal compromise, and disc herniation location taken from MRI images of patients with symptomatic single-level lumbar herniated intervertebral discs upon initial presentation to a spine surgeon, were predictive of the need for surgical treatment. STUDY DESIGN/SETTING: This is a retrospective case matched study of patient MRI images in the senior author's private practice. PATIENT SAMPLE: From a pool of 332 patients with sciatica caused by lumbar intervertebral disc herniations at our institution, 65 patients had surgery, of which MRI images were available and analyzed on 44 patients. Forty-four additional patients were randomly selected from the remaining 267 original group as nonoperative controls. METHODS: The axial MRI image showing the largest canal compromise by the herniated disc was selected for measurements. Using T1- and T2-weighted images, the areas of interest were digitally scanned at high resolution. The canal area and disc herniation area measurement were calculated from the total number of pixels per cross-sectional area, multiplied by a scan correction factor, mm(2) /pixel. Disc herniation locations were classified into either central or paracentral. The percent canal compromise was obtained by disc herniation area divided by canal cross-section area and multiplied by 100. RESULTS: The surgical group's overall mean herniated disc area was 219.6 square millimeter (mm(2)), 179.8 at L4-5, and 267.4 at L5-S1. The nonoperative group's overall mean herniated disc area was 178.4 mm(2), 135.1 at L2-3, 160.3 at L4-5, and 207.4 at L5-S1. The surgical group's overall mean canal cross-sectional area was 471.8 mm(2), 418.6 at L4-5, and 535.6 at L5-S1. The nonoperative group's overall mean canal cross-sectional area was 541.3 mm(2), 518.1 at L2-3, 446.8 at L4-5, and 669.9 at L5-S1. The overall percent canal compromise ratio in the surgery group was 46.7%, 44.1% at L4-5, and 49.8% at L5-S1. The overall percent canal compromise in the nonoperative group was 34.2%, 34.1% at L2-3, 36.1% at L4-5, and 31.8% at L5-S1. The percent canal compromise in central herniations at L4-5 level was 53.0% in the surgical group, and 32.8% in the nonoperative group; at the L5-S1 level surgical group percent canal compromise was 64.1% and in the nonoperative group canal compromise was 27%. L4-L5 level paracentral herniations canal compromise was 36.7% in the surgical group compared with 42.5% canal compromise in the nonoperative group. At the L5-S1 level the canal compromise was 45% in the surgical group and 34.8% in the nonoperative group. CONCLUSIONS: Our findings show a trend for patients treated with surgery to have larger disc herniation areas and smaller canal cross-section areas, corresponding to larger percent canal compromise than the nonoperative group. Centrally located herniations followed this trend closely at all levels studied. However, the paracentral herniation at the L4-5 level does not follow this trend, possibly because paracentral disc herniation clinical course is determined more by herniation location rather than the overall herniation size.     

Development of grating acuity in infants with regressed stage 3 retinopathy of prematurity

The acuity card procedure was used to measure grating acuity in 17 infants with regressed Stage 3 retinopathy of prematurity (ROP) who had no lasting anatomic changes in the retina or optic nerve. Results were compared with those of 28 healthy preterm infants and 28 infants matched by birth weight and gestational age who did not have Stage 3 ROP. Infants in the ROP group showed delayed grating acuity development until 2 years of age. This difference among groups was significant at the 3-5- and 10-12-month test ages but not at the 0-1-, 8-9-, and 16-18-month test ages. Post hoc analyses indicated that the delay in acuity development shown by the ROP group was due to the poor acuity scores of the infants in that group who had central nervous system abnormalities of periventricular leukomalacia or severe (Grade III or IV) intraventricular hemorrhage. When the data of these infants were removed from the analysis, the ROP group showed acuity development similar to that of both the healthy preterm group and the group of infants with matched birth weights and gestational ages who did not have Stage 3 ROP.     

Diphenhydramine kinetics following intravenous, oral, and sublingual dimenhydrinate administration

Eight healthy volunteers received 50 mg of dimenhydrinate, a theoclate salt of diphenhydramine, orally, sublingually, and intravenously on three separate occasions in random sequence. Plasma diphenhydramine concentrations during 12 h after each dose were measured by gas-liquid chromatography with nitrogen-phosphorous detection. Mean peak plasma concentrations after sublingual administration were slightly lower than after oral dosage (38.3 vs 47.8 ng ml-1), and the time of peak concentration was similar (2.6 vs 2.3 h after dose). These differences did not reach statistical significance. The mean total area under the plasma concentration-time curve (AUC) for sublingual administration was slightly but not significantly smaller than after oral dosage (221 vs 270 h ng ml-1). Systemic availability of diphenhydramine after sublingual dimenhydrinate, measured by the ratio of oral AUC to intravenous AUC, was slightly less than after oral dimenhydrinate (0.58 vs 0.69, NS), and both were significantly less than 1.0. Thus sublingual and oral administration of dimenhydrinate result in comparable, but incomplete, systemic availability of diphenhydramine.     

Maturation of executive function in autism.

BACKGROUND: Executive dysfunction has been reported at different ages in autism. It is not clear however, when this impairment emerges or how its expression is affected by development. METHODS: 61 non-mentally retarded autism participants (AUT) and 61 age, gender, and IQ matched typically developing participants (CON) were assessed with two oculomotor executive function tasks, the oculomotor delayed response task (ODR) and the antisaccade task (AS), as well as a visually-guided saccade sensorimotor task (VGS). RESULTS: The AUT group demonstrated impairments in response inhibition and spatial working memory at all ages tested. Developmental improvements in speed of sensorimotor processing and voluntary response inhibition were similar in both groups indicating sparing of some attentional control of behavior. Developmental progression in the speed of initiating a cognitive plan and maintaining information on line over time, however, was impaired in the AUT group indicating abnormal development of working memory. CONCLUSIONS: These results indicate that while executive dysfunction is present throughout development, there is evidence for both typical and atypical developmental progression of executive functions in autism. The plasticity suggested by the developmental improvements may have implications regarding appropriate developmental epochs and types of interventions aimed at enhancing cognitive capacities in individuals with autism.     

Methylation, a major mechanism of p16/CDKN2 gene inactivation in head and neck squamous carcinoma.

We studied 11 head and neck squamous carcinoma (HNSC) cell lines and 46 primary tumors for p16 gene status by protein, mRNA, and DNA genetic/epigenetic analyses to determine the incidence, the mechanism(s), and the potential biological significance of its inactivation. Of the 11 cell lines, only 1 showed intact p16 and 10 lacked its protein and mRNA; DNA analysis of these 10 cell lines showed 2 homozygous deletions, 6 methylations at exon 1 and 2, and 2 with no detectable abnormalities. In primary tumors, 16 (34.7%) of the 46 showed detectable p16 protein and mRNA; of these, 12 had no DNA abnormalities and 4 had only exon 2 methylation. Loss of p16 expression was found in three tumors with concurrent mutation at exon 2 and methylation at exon 2 (two) and both 1 and 2 (one). Of the 30 tumors that lacked p16 protein, 27 also lacked mRNA, 1 had detectable p16 mRNA, and 2 failed RT-PCR amplification. Twenty-two of the thirty tumors showed DNA alterations and eight manifested no abnormalities; DNA alterations comprised 6 homozygous deletions, 2 concurrent mutations and methylation of exon 2, and 13 with methylation at exon 1 and exons 1 and 2 (12 with methylation only and 1 with mutation) at exon 1. Except for patients' gender (P = 0.02), no significant correlation between p16 and clinicopathological factors was observed. We conclude that in HNSC 1) intragenic p16 alterations are infrequent events, 2) methylation of exon 1 constitutes a common mechanism in silencing the p16 gene, 3) p16 inactivation may play an important role in the early development and progression of HNSC, and 4) no association between p16 alterations and conventional clinicopathological factors was noted in this cohort.     

Salivary dermal analogue tumors arising in lymph nodes

Dermal analogue tumor, an unusual type of monomorphic salivary adenoma, occurs in the parotid gland and rarely in other salivary tissues. This report describes three patients with dermal analogue tumors arising from ectopic salivary tissue in lymph nodes. Two tumors appeared in the periparotid lymph nodes and one in the lateral upper cervical region. All of the patients were men, aged 50 to 60 years, who all had a painless neck mass for 1 year or longer. Currently, the patients are free of disease 14, 3, and 2 years, respectively, after surgical excision. Dermal analogue monomorphic adenomas join several other salivary tumors in possible intranodal origin and should not be confused with metastases.     

Studies on the mechanism of 3-deazaguanine cytotoxicity in L1210-sensitive and -resistant cell lines

Summary 3-Deazaguanine (3-DG), a purine analogue, has unusual antitumor activity against experimental mammary tumor models and a number of other solid tumors. Others have shown that mutant CHO cells deficient in hypoxanthine guanine phosphoribosyl transferase (HGPRTase) or adenine phosphoribosyl transferase (APRTase) are resistant to 3-DG. We developed a L1210 cell line resistant to 3-DG, L1210/3-DG, by subculturing the parent L1210/0 cells in the presence of increasing concentrations of 3-DG. The IC₅₀ was 3.5 M and 620 M for L1210/0 and L1210/3-DG, respectively. Cytotoxicity studies proved the resistance to be stable. Examination of the baseline-specific activity of HGPRTase and APRTase showed that the former was 118-fold lower in L1210/3-DG than in L1210/0, and the latter demonstrated no difference. A 4-h treatment of the cell lines at IC₅₀ doses showed 48% and 23% reductions in IMP dehydrogenase in L1210/0 and L1210/3-DG, respectively. The rate of de novo purine biosynthesis was studied by using [¹⁴C]formic acid. Formate flux increased 2-fold in L1210/3DG in concert with the observed deficiency of HGPRTase in the cell line. 3-DG uptake was studied with [¹⁴C]-labelled compound. The total radioactivity was 9-fold higher in L1210/0 than in L1210/3-DG at 2 h. Subsequent chromatographic separation of radioactivity showed the 3-DG and 3-deazaguanosine pools of the drug to be equal in both lines. However, 3-DG nucleotide pools at 1 min and 2 h were 2.5-fold and 16-fold lower, respectively, in L1210/3-DG than in L1210/0. 3-DG incorporation studies with radiolabelled drug demonstrated that 3-deazaguanine is incorporated in the acid-insoluble fraction of the cell. These studies conclude that HGPRTase, and not APRTase, is required for the activation of drug. Inhibition of IMP dehydrogenase is partially responsible for antitumor activity of the drug. The incorporation of drug into nucleic acids may be a major mechanism for its antitumor activity. Further studies using a cloned cDNA probe for hypoxanthine guanine phosphoribosyltransferase (HGPRT) demonstrated no change in the DNA arrangements of the L1210/3-DG cell line, and Northern blot analysis showed approximately equal expression of mRNA in both cell lines.Abbreviations used APRTase adenine phosphoribosyltransferase - HGPRTase Hypoxanthine guanine phosphoribosyltransferase - IMPD Inosine mono-phosphate dehydrogenase - PRPP 5-Phosphorylribose-1-pyrophosphate - AOPCP , -Methyleneadenosine 5-diphosphate - NAD Nicotineamide dinucleotide - EDTA Ethylenediamine tetra acetic acid Presented at annual meeting of American Association of Cancer Research in May, 1986Supported in part by Warner-Lambert Company, Ann Arbor, Michigan