Tumors of the optic nerve

This is a review of primary and secondary tumors of the optic nerve. The emphasis is on optic nerve gliomas and meningiomas.Optic nerve gliomas are slowly growing astrocytic neoplasms of the anterior visual pathways, the majority of which occur within the first two decades of life with equal sex incidence in about 1 of 200,00 patients presenting with eye complaints. The incidence is greater in neurofibromatosis. The typical presentation is visual impairment in a verbal pre-school child with optic canal enlargement and optic atrophy. An intraorbital location of the tumor leads to axial, irreducible, non-pulsatile proptosis. An intracranial location may disturb hypothalamic and pituitary function and produce hydrocephalus. Ocular findings may also include limited motility on a mechanical-restrictive basis, a pupillary relative afferent defect, nystagmus, and variable, non-specific visual field defects. Roentgenographic studies may show concentric unilateral enlargement of the optic canal with preservation of a well corticated margin, a fossa under the anterior clinoid process in continuity with the optic canal (J-shaped sella), and findings of increased intracranial pressure. On pathologic examination the tumor is a smooth, fusiform, intradural enlargement of the optic nerve. Histologically there is proliferation of elongated (pilocytic) astrocytes in reticulated patterns with intervening microcystic spaces containing mucosubstance and surrounding reactive hyperplasia of the arachnoid. Mitoses are not found. The diagnosis is clinical X-ray studies and brain scan should be performed. The differential diagnosis is that of unilateral proptosis in a child and includes acute ethmoiditis, hyperthyroidism, craniostenosis, other neoplasms, Hand-Schuller-Christian disease, and orbital hemorrhage due to trauma. Surgical resection is performed in cases with unilateral optic nerve involvement, the surgical approach being determined by tumor location. Bilateral or chiasmal cases are treated with radiotherapy when progression occurs. Malignant optic nerve gliomas and optic nerve hyperplasia are also discussed.Optic nerve meningiomas arise from the nerve sheath and are to be distinguished from orbital meningiomas arising from ectopic arachnoidal cells or those secondarily involving the orbit by extension from adjacent sites. Up to 80% of orbital meningiomas occur in females, in two age peaks, 25% in the first decade, and the rest in the 5th decade. Meningiomas present with visual loss and may produce proptosis, papilledema and/or optic atrophy, retinal striae, opticociliary shunts, limitation of extra-ocular movements, and lid edema. Signs of von Recklinghausen's disease should be sought. X-rays are the mainstay of diagnosis. Orbital meningiomas are composed of cells in sheets or in whorls with some spindle shaped cells. Calcifications are typical. Usually the dura is penetrated and the orbit invaded. Primary orbital meningiomas are locally infiltrating but do not metastasize. Complete local excision en bloc is recommended. Local recurrences may require reoperation; however, long term survival is excellent.Optic nerve head tumors are mostly benign hamartomatous proliferations of glial, melanocytic, or vascular tissue in the form of the astrocytic hamartomas of tuberous sclerosis, melanocytomas, and angiomatous malformations. There may also be primary or reactive proliferations of the juxtapapillary pigment epithelium. Metastatic lesions of the optic nerve are rare, breast and lung carcinomas accounting for most. The optic nerve may be infiltrated by neopastic cells in the leukemias and lymphomas. The optic nerve may also be involved by inflammatory processes, notably sarcoidosis. Optic nerve medulloepitheliomas are highly malignant and must receive aggressive surgical treatment.From the Edward S. Harkness Eye Institute, Columbia-Presbyterian Medical Center, New York, New York 10032.     

Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies.

PURPOSE: Recently, we reported that a large number of human hepatocellular cancer (HCC) cell lines were auxotrophic for arginine. Here we report the results obtained with the amino acid-degrading enzyme arginine deiminase (ADI) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) as a means of lowering plasma arginine to treat HCC. The study was a cohort dose-escalation phase I/II study. PATIENTS AND METHODS: Pharmacodynamic studies indicated an ADI-SS PEG 20,000 mw dose level of 160 U/m(2) was sufficient to lower plasma arginine from a resting level of approximately 130 micromol/L to below the level of detection (< 2 micromol/L) for more than 7 days, a dose later defined as the optimal biologic dose. All patients were to receive three cycles at the optimum biologic dose. RESULTS: This therapy was well tolerated, even in patients who had no detectable plasma arginine for 3 continuous months of therapy. Of the 19 patients enrolled, two had a complete response, seven had a partial response, seven had stable disease, and three had progressive disease. The median survival for the 19 patients enrolled on this study was 410 days, with four patients still alive at present (> 680 days). CONCLUSION: Elimination of all detectable plasma arginine in patients with HCC was well tolerated and seemed to be effective in the treatment of some patients with HCC. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with HCC as well as other human tumors auxotrophic for arginine is warranted.     

Treatment of children and adolescents with stage II testicular and stages I and II ovarian malignant germ cell tumors: A Pediatric Intergroup Study--Pediatric Oncology Group 9048 and Children's Cancer Group 8891.

PURPOSE: To determine whether children with localized gonadal malignant germ cell tumors (MGCT) stage II testicular and stages I and II ovarian treated with four cycles of standard-dose cisplatin combined with etoposide and low-dose bleomycin (PEB) have an event-free survival (EFS) of at least 85% without significant toxicity. PATIENTS AND METHODS: Between May 1990 and July 1995, eligible pediatric patients with stage II or recurrent from stage I (as a stage II) testicular MGCT and stages I and II ovarian MGCT were enrolled onto this Pediatric Oncology Group and Children's Cancer Group study. PEB chemotherapy consisted of bleomycin 15 U/m2 on day 1, cisplatin 20 mg/m2/d on days 1 to 5, and etoposide 100 mg/m2/d on days 1 to 5. Patients received four cycles of therapy at 21-day intervals. RESULTS: Seventy-four patients with a median age of 10.5 years (range, 8.7 months to 16.7 years) were enrolled. Primary sites included: stage II testicular (n = 17), stage I ovarian (n = 41), and stage II ovarian MGCT (n = 16). Treatment with standard PEB resulted in 6-year EFS of 95% and overall survival (OS) of 95.7%. EFS and OS by primary site were as follows: stage II testicular, 100% and 100%; stage I ovarian, 95.1% and 95.1%; and stage II ovarian, 87.5% and 93.8%, respectively. Two patients died from recurrent disease, and one patient died of secondary acute myelocytic leukemia. Infrequent grade 3 to 4 hematologic toxicity was reported. No grade 3 to 4 renal, pulmonary, or ototoxicity was observed. CONCLUSION: Combination chemotherapy with PEB results in excellent EFS and OS with minimal toxicity in children and adolescents with localized gonadal MGCT.     

New non-cocaine-containing topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations

OBJECTIVE: To compare the effectiveness of three new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine, tetracaine-phenylephrine [tetraphen], and tetracaine-lidocaine-phenylephrine) to that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: The emergency department of an urban children's hospital. PARTICIPANTS: Children 1 year of age or older with a laceration /= 5 years of age using a visual analogue scale (VAS). Suture technicians, research assistants, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an anesthetic effectiveness scale. RESULTS: There was consistently no difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. A statistically significant difference was seen among anesthetics when comparing VAS and Likert scale scores of suture technicians and Likert scale scores of research assistants. Based on post hoc analyses, these statistically significant differences were between TAC and prilocaine-phenylephrine (suture technician VAS and Likert scale) and between TAC and tetracaine-lidocaine-phenyl-ephrine (suture technician Likert scale), but not between TAC and tetraphen. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.2 VAS units for each of the observer groups. Based on anesthetic effectiveness scale scores, the three new topical preparations collectively performed significantly better on the face and scalp than on the extremities (relative risk = 1.83; 95% confidence interval 1.20 < relative risk < 2.79). CONCLUSION: This study demonstrated the effectiveness and safety of three new non-cocaine-containing topical anesthetics. Consistently, there was no statistical difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. Tetraphen offers an effective alternative to TAC during laceration repair in children.     

Increased placental apoptosis in intrauterine growth restriction

OBJECTIVES: Our purpose was to investigate a possible role for apoptosis in the pathophysiologic mechanisms of intrauterine growth restriction. STUDY DESIGN: Placental samples were obtained from 43 uncomplicated third-trimester pregnancies and from 26 pregnancies complicated by intrauterine growth restriction. The definition used to identify cases of intrauterine growth restriction depended on three criteria: clinical evidence of suboptimal growth, ultrasonographic evidence of deviation from an appropriate growth percentile, and individualized birth weight ratios <10th percentile. Light microscopy was used to quantify the incidence of apoptosis. Electron microscopy and TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling) staining were used to confirm the occurrence of apoptosis. RESULTS: Quantification of apoptosis (medians and interquartile ranges) resulted in the following values: normal third trimester (n = 43) 0.14% of cells (0.08% to 0.20%) and intrauterine growth restriction third trimester (n  = 26) 0.24% of cells (0.16% to 0.29%). The incidence of apoptosis was significantly higher in placentas from pregnancies with intrauterine growth restriction compared with normal third-trimester placentas (p < 0.01, Mann Whitney U test). CONCLUSIONS: These results suggest that apoptosis may play a role in the pathophysiologic mechanisms of intrauterine growth restriction.(Am J Obstet Gynecol 1997;177:401)     

Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain

CONTEXT: Although chest pain is widely considered a key symptom in the diagnosis of myocardial infarction (MI), not all patients with MI present with chest pain. The extent to which this phenomenon occurs is largely unknown. OBJECTIVES: To determine the frequency with which patients with MI present without chest pain and to examine their subsequent management and outcome. DESIGN: Prospective observational study. SETTING AND PATIENTS: A total of 434,877 patients with confirmed MI enrolled June 1994 to March 1998 in the National Registry of Myocardial Infarction 2, which includes 1674 hospitals in the United States. MAIN OUTCOME MEASURES: Prevalence of presentation without chest pain; clinical characteristics, treatment, and mortality among MI patients without chest pain vs those with chest pain. RESULTS: Of all patients diagnosed as having MI, 142,445 (33%) did not have chest pain on presentation to the hospital. This group of MI patients was, on average, 7 years older than those with chest pain (74.2 vs 66.9 years), with a higher proportion of women (49.0% vs 38.0%) and patients with diabetes mellitus (32.6% vs 25. 4%) or prior heart failure (26.4% vs 12.3%). Also, MI patients without chest pain had a longer delay before hospital presentation (mean, 7.9 vs 5.3 hours), were less likely to be diagnosed as having confirmed MI at the time of admission (22.2% vs 50.3%), and were less likely to receive thrombolysis or primary angioplasty (25.3% vs 74.0%), aspirin (60.4% vs 84.5%), beta-blockers (28.0% vs 48.0%), or heparin (53.4% vs 83.2%). Myocardial infarction patients without chest pain had a 23.3% in-hospital mortality rate compared with 9.3% among patients with chest pain (adjusted odds ratio for mortality, 2. 21 [95% confidence interval, 2.17-2.26]). CONCLUSIONS: Our results suggest that patients without chest pain on presentation represent a large segment of the MI population and are at increased risk for delays in seeking medical attention, less aggressive treatments, and in-hospital mortality. JAMA. 2000;283:3223-3229     

Dietary fructose intolerance: diet modification can impact self-rated health and symptom control.

Carbohydrate intolerance to lactose is widely accepted as a cause of gastrointestinal symptoms, but controversy persists on how important dietary fructose intolerance (DFI) is in causing gastrointestinal pain and suffering and if an elimination diet can control the presenting complaints. The objective of this study was to identify a group of well-defined DFI patients and explore whether dietary education followed by dietary compliance could control symptoms and improve quality of life. During a 5-year period, patients referred to a pancreato-biliary clinic were evaluated for dietary carbohydrate intolerances if they presented with gastrointestinal pain and/or gas and/or bloating and/or diarrhea. Patients were tested with a standardized mixture of glucose, fructose, and lactose diluted in sterile water. End-expiratory breath samples were collected for hydrogen and methane measurement. Symptoms were scored using a 9-point symptom questionnaire. The patients underwent in-depth education by a dietician, and were provided with access to a cookbook, a newsletter, and a support group. A dietary questionnaire was used to evaluate compliance with the fructose-restricted diet. DFI can cause significant gastrointestinal symptoms that may not respond to medications or surgical interventions. Symptoms can improve and self-rated health does improve in DFI patients willing to adhere to a low fructose diet.     

Sex differences in response to red and blue light in human primary visual cortex: a bold fMRI study

Studies using a variety of investigative methods, including functional brain imaging and electroencephalography (EEG), have suggested that changes in central nervous system (CNS) dopamine function result in altered visual system processing. The discovery of abnormal retinal blue cone, but not red cone, electroretinogram in association with cocaine withdrawal and Parkinson's disease suggests that visual system response to blue light might be a marker for CNS dopamine tone. As there are numerous sex-related differences in central nervous system dopamine function, we predicted that blue and red light stimulation would produce sex-specific patterns of response in primary visual cortex when studied using the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique. We analyzed the BOLD response to red and blue light in male and female human volunteers (N=20). Red and blue light responses in primary visual cortex (V1) to stepped intensities of red and blue light were compared by sex for threshold to detectable BOLD signal increase and for stimulus intensity vs. BOLD signal response. Near threshold, males and females showed similar BOLD signal change to red light, but males showed a threefold greater increase (0.52%) to blue light stimulation when compared to females (0.14%). Log-linear regression modeling revealed that the slope coefficients for the red light stimulus intensity vs. signal change curve were not significantly different for males and females (z=0.995, P=0.320), whereas the slope coefficients for the blue light stimulus intensity vs. signal change curve were significantly larger in males (z=2.251, P=0.024). These findings support a sex and color-dependent differential pattern of primary visual cortical response to photic stimulation and suggest a method for assessing the influence of specific dopamine agonist/antagonist medications on visual function.