Neuronal Control of Esophageal Peristalsis and Its Role in Esophageal Disease.

PURPOSE OF REVIEW: Esophageal peristalsis is a highly sophisticated function that involves the coordinated contraction and relaxation of striated and smooth muscles in a cephalocaudal fashion, under the control of central and peripheral neuronal mechanisms and a number of neurotransmitters. Esophageal peristalsis is determined by the balance of the intrinsic excitatory cholinergic, inhibitory nitrergic and post-inhibitory rebound excitatory output to the esophageal musculature. RECENT FINDINGS: Dissociation of the longitudinal and circular muscle contractions characterizes different major esophageal disorders and leads to esophageal symptoms. Provocative testing during esophageal high-resolution manometry is commonly employed to assess esophageal body peristaltic reserve and underpin clinical diagnosis. Herein, we summarize the main factors that determine esophageal peristalsis and examine their role in major and minor esophageal motility disorders and eosinophilic esophagitis.

Treatment of acute bleeding in acquired haemophilia A with recombinant activated factor VII: analysis of 10-year Japanese postmarketing surveillance data.

INTRODUCTION: Patients with acquired haemophilia A (AHA) have autoantibodies against factor VIII (FVIII), and may develop spontaneous bleeding that requires treatment with FVIII inhibitor bypassing agents such as recombinant activated FVII (rFVIIa, NovoSeven® ). However, data regarding the use of rFVIIa are limited. AIM: To investigate the use, efficacy and safety of rFVIIa for the treatment of AHA by analysis of 10-year multicentre Japanese postmarketing surveillance data. METHODS: Treatment regimens, haemostatic efficacy and adverse events were recorded for rFVIIa therapy of AHA patients with bleeding episodes. Treatment was evaluated as markedly effective, effective, moderate or ineffective. RESULTS: Data were collected for 371 bleeding episodes in 132 patients. Bleeding improved after rFVIIa therapy in 92% of episodes (markedly effective in 41%, effective in 10%, moderate in 41%). The response rate was significantly better in patients who received an initial dose of ≥90 µg kg-1 than in those who received an initial dose of <90 µg kg-1 . The response rate was also significantly better when rFVIIa was administered earlier after the onset of bleeding. Twelve serious adverse events were recorded in six patients, including five serious thromboembolic events in three patients who were all elderly with significant comorbidities. CONCLUSION: This is the largest, single-country study of rFVIIa therapy in AHA patients reported to date. The Japanese surveillance data show comparable efficacy and safety to prior multinational studies. Doses of 90-120 µg kg-1 and prompt initiation of treatment may be important to achieve good bleeding control.

Nuclear factor kappa B plays a pivotal role in polyinosinic-polycytidylic acid-induced expression of human ß-defensin 2 in intestinal epithelial cells.

Intestinal epithelial cells (IECs) play an important role in protecting the intestinal surface from invading pathogens by producing effector molecules. IECs are one of the major sources of human beta-defensin 2 (hBD-2), and can produce it in response to a variety of stimuli. Although IECs express Toll-like receptor 3 (TLR-3) and can respond to its ligand, double-stranded RNA (dsRNA), hBD-2 expression in response to dsRNA has not been elucidated. In the present study, using an artificial analogue of dsRNA, polyinosinic-polycytidylic acid (poly I:C), we investigated whether the human IEC line, HT-29, can produce hBD-2 in response to poly I:C. HT-29 cells can express hBD-2 mRNA only when stimulated with poly I:C. The induction of hBD-2 mRNA expression was observed at 3 h after stimulation and peaked at 12 h of post-stimulation. Pre-incubation of the cells with nuclear factor kappa B (NF-κB)-specific inhibitor, l-1-4'-tosylamino-phenylethyl-chloromethyl ketone (TPCK) and isohelenine abolished the expression of hBD-2. Detection of the poly I:C signal by TLR-3 on the surface of HT-29 cells was revealed by pre-incubating the cells with anti-TLR-3 antibody. The 5'-regulatory region of the hBD-2 gene contains two NF-κB binding sites. A luciferase assay revealed the importance of the proximal NF-κB binding site for poly I:C-induced expression of hBD-2. Among NF-κB subunits, p65 and p50 were activated by poly I:C stimulation and accumulated in the nucleus. Activation of the p65 subunit was investigated further by determining its phosphorylation status, which revealed that poly I:C stimulation resulted in prolonged phosphorylation of p65. These results indicate clearly that NF-κB plays an indispensable role in poly I:C induced hBD-2 expression in HT-29 cells.

Estimating the Net Utility Gains Among Donors and Recipients of Adult Living Donor Kidney Transplant.

OBJECTIVES: Living donor kidney transplant relieves the disease burden of patients with end-stage renal disease but may shorten donor life expectancy; however, their quality of life (QOL) is preserved. Nevertheless, the magnitude of the net gain of this procedure is unknown. We evaluated the QOL of both donors and recipients concurrently and calculated the net utility gain. METHODS: We recruited 210 subjects who visited the kidney transplantation clinic of a university hospital. Subjects were asked to complete the 5-level EQ-5D-based questionnaire, and patient characteristics were extracted from their medical records. We performed multivariate tobit models analysis to evaluate the QOL change caused by transplant surgery and subsequently ran computational simulations to determine the net utility gains of donors and recipients. We also performed sensitivity analyses. RESULTS: After excluding 16 answers with missing data, we analyzed 203 answers in total. After the transplant surgery, recipients gained 0.07 in utility value while donors lost 0.04. In the net utility analysis, we found that the quality-adjusted life years gained ranged from 7.2 to 7.8 in the most favorable case observed in the combination of middle-aged recipients and elderly donors. Assuming no utility discount, the most favorable combination was that with older donors and younger recipients. CONCLUSIONS: These findings indicated that the QOL improvement in recipients was larger than the loss among donors. When calculating the net utilities, a combination of middle-aged recipients and elderly donors yielded the largest net utility, but this was likely derived from assumption in the discount of QOL.

Recurrent Aphthous Stomatitis Caused by Cytomegalovirus, Herpes Simplex Virus, and Candida Species in a Kidney Transplant Recipient: A Case Report.

Recipients of organ transplants are immunosuppressed and at high risk of oral infection. Oral diseases are often neglected compared with infections of other organs that typically confer higher morbidity. However, severe local symptoms hinder oral intake, decrease quality of life, and are sometimes lethal. Here we describe a case of a 57-year-old woman who developed recurrent aphthous stomatitis after kidney transplantation; the cause of the infection was complex and included cytomegalovirus, herpes simplex virus, and Candida species. Since misdiagnosis of oral diseases impairs patient quality of life and increases morbidity, clinicians should be aware of possible etiologies of oral infections in renal transplant recipients.

Universal modeling of weak antilocalization corrections in quasi-two-dimensional electron systems using predetermined return orbitals.

We have developed a method to calculate the weak localization and antilocalization corrections based on the real-space simulation, where we provide 147 885 predetermined return orbitals of quasi-two-dimensional electrons with up to 5000 scattering events that are repeatedly used. Our model subsumes that of Golub [L. E. Golub, Phys. Rev. B 71, 235310 (2005)PRBMDO1098-012110.1103/PhysRevB.71.235310] when the Rashba spin-orbit interaction (SOI) is assumed. Our computation is very simple, fast, and versatile, where the numerical results, obtained all at once, cover wide ranges of the magnetic field under various one-electron interactions H^{'} exactly. Thus, it has straightforward extensibility to incorporate interactions other than the Rashba SOI, such as the linear and cubic Dresselhaus SOIs, Zeeman effect, and even interactions relevant to the valley and pseudo spin degrees of freedom, which should provide a unique tool to study new classes of materials like emerging 2D materials. Using our computation, we also demonstrate the robustness of a persistent spin helix state against the cubic Dresselhaus SOI.

Increased intensity of acute graft-versus-host disease after reduced-intensity bone marrow transplantation compared to conventional transplantation from an HLA-matched sibling in children.

Eight children underwent reduced-intensity stem cell transplantation (RIST) from an HLA-matched sibling. They received a fludarabine-melphalan based preparative regimen. Stem cell source was bone marrow, and GVHD prophylaxis consisted of cyclosporine A alone. Acute GVHD grade II-IV and grade III-IV were observed in four (50%) and three (37.5%), respectively, out of these eight patients. This incidence was significantly higher than that after conventional bone marrow transplantation, without severe tissue damage, in the same setting of stem cell source and GVHD prophylaxis. Although the number of patients is small, our results suggest that incidence of acute GVHD after RIST for children is significant. It should be remembered that RIST for children does not seem to be an easy transplant procedure from the viewpoint of acute GVHD, although RIST is less toxic.

Unrelated donor bone marrow transplantation for 100 pediatric patients: a single institute's experience.

In all, 100 unrelated donor bone marrow transplantations (UD-BMT) were performed in our institute between October 1993 and January 2003. Of 93 evaluable patients, 73 patients had hematological malignancy, 13 had nonmalignancy and seven had lymphoproliferative disease. The estimated 9-year event-free survival (EFS) rate was 57.1+/-5.5% in all patients. In the following analyses of the patients with hematological malignancy, the standard group had significantly better EFS than the high-risk group (61.5+/-7.0 vs 35.6+/-9.7%, P=0.02), and the EFS rate of the tacrolimus (FK-506)+methotrexate (MTX)+/-methylprednisolone prophylactic group for graft-versus-host disease was superior to that of the FK-506 without MTX group (75.7+/-8.0 vs 55.8+/-7.6%, P=0.02). When we compared the EFS rates of the FK506+MTX+/-methylprednisolone (mPSL) group and the HLA-matched related donor BMT group in our institute, these were almost similar (75.7+/-8.1 vs 68.4+/-9.3%). Therefore, UD-BMT using FK-506+MTX+/-mPSL is a safe and useful method for children with hematological malignancy who require allogeneic BMT.

Cytotoxic chemotherapy successfully induces durable complete remission in 2 patients with mosquito allergy resulting from Epstein-Barr virus-associated T-/natural killer cell lymphoproliferative disease.

Recent findings indicate that Epstein-Barr virus (EBV)-infected T-/natural killer (NK) cells play an important role in the pathogenesis of mosquito allergy, and most patients with mosquito allergy die early in life if not properly treated. Over the last 7 years, we have been using combination chemotherapy and allogeneic stem cell transplantation for the treatment of EBV-associated T-/NK cell lymphoproliferative disease (LPD) in which chronic active EBV infection and mosquito allergy were included. As of this writing, we have successfully treated 2 patients with mosquito allergy with chemotherapy in which EBV-infected T-/NK cells were eradicated. The findings suggest the possible role of chemotherapy in the treatment of EBV-associated T-/NK cell LPD.

Lack of the Polycomb-group gene rae28 causes maturation arrest at the early B-cell developmental stage.

The rae28 gene (rae28) is a murine homologue of the Drosophila polyhomeotic gene, which is a member of the Polycomb-group genes. In this study, we examined the role of rae28 in lymphocyte development. Because homozygous rae28-deficient (rae28-/-) mice died in the perinatal period, we examined lymphocyte development by generating chimeric mice reconstituted with green fluorescence protein-labeled mutant fetal liver cells as well as in in vitro culture systems. We further examined RAE28 expression by reverse transcriptase polymerase chain reaction assay in human leukemic cells with B-lineage acute lymphoblastic leukemia (ALL). Severe B-cell maturation arrest was observed in rae28-/- between pro- and pre-B lymphocyte stages. B-cell development was also delayed in heterozygous neonates. Furthermore, interleukin-7-dependent colony-forming ability was impaired not only in homozygous lymphocytes but also in heterozygotes. Its human homologue, RAE28, is located on chromosome 12p13, which frequently is associated with chromosomal abnormalities and loss of heterozygosity in patients with hematologic malignancies. To determine whether a link exists between RAE28 and leukemia, we examined RAE28 expression in leukemic cells from pediatric patients with B-lineage ALL. RAE28 expression was not detected in four B-cell precursor ALL cases of a total of 43 examined, although RAE28 is normally expressed constitutively during the process of B-cell maturation as assessed in isolated cell populations. rae28 plays an important role in the early B-cell developmental stage in a gene dosage-dependent manner. Furthermore, the human RAE28 locus may provide a candidate gene causing the molecular pathogenesis of childhood B-cell precursor ALL.

Thallium-201 uptake in eosinophilic granuloma of the frontal bone: comparison with technetium-99m-MDP imaging.

An 11-yr-old female presented with a 6-wk history of left upper lid tenderness and left eye lacrimation. Left lateral supraorbital mass and left preauricular lymph node were the only significant physical examination findings. On skull x-ray, a left frontal bone defect was noted. CT and MRI showed a soft-tissue mass in the area of the bone defect. Bone scintigraphy exhibited peripheral uptake within the central photon deficient area. With 201TI SPECT, high uptake was noted on early and delayed images. Diagnosis of eosinophilic granuloma was performed by biopsy. Since thallium uptake was seen in the area where photon deficiency was exhibited by 99mTc-MDP scintigraphy, we speculate that thallium SPECT could detect eosinophilic granuloma when radiographic skeletal survey or radionuclide bone scan are equivocal. It could also rule out multiple bone involvement and recurrence or regrowth after therapy.

Isoforms of nitric oxide synthase in the optic nerves of rat eyes with chronic moderately elevated intraocular pressure.

PURPOSE: To investigate the hypothesis that nitric oxide (NO) in the optic nerve heads of rats with chronic moderately elevated intraocular pressure (IOP) contributes to neurotoxicity of the retinal ganglion cells, the presence of the three isoforms of nitric oxide synthase (NOS) was determined in the tissue. METHODS: Unilateral chronic moderately elevated IOP was produced in rats by cautery of three episcleral vessels. Histologic sections of optic nerves from eyes with normal IOP and with chronic moderately elevated IOP were studied by immunohistochemistry and by immunoblot analysis. Polyclonal antibodies to NOS-1, NOS-2, NOS-3, and glial fibrillary acidic protein (GFAP) were localized with immunoperoxidase. RESULTS: In the optic nerve of rat eyes with normal IOP, NOS-1 was constitutively present in astrocytes, pericytes and nerve terminals in the walls of the central artery. NOS-2 was not present in eyes with normal IOP. In these eyes, NOS-3 was constitutively present in the vascular endothelia of large and small vessels. Rat eyes treated with three-vessel cautery had sustained elevated IOP (1.6 fold) for at least 3 months. In these eyes, no obvious changes in NOS-1 or NOS-3 were noted. However, at time points as early as 4 days of chronic moderately elevated IOP, NOS-2 appeared in astrocytes in the optic nerve heads of these eyes and persisted for up to 3 months. Immunoblot analysis did not detect differences in NOS isoforms. CONCLUSION: The cellular distributions of constitutive NOS isoforms in the rat optic nerve suggest physiological roles for NO in this tissue. NOS-1 in astrocytes may produce NO as a mediator between neighboring cells. NO, produced by NOS-1 in pericytes and nitrergic nerve terminals and by NOS-3 in vascular endothelia, is probably a physiological vasodilator in this tissue. In eyes with chronic moderately elevated IOP, NOS-2 is apparently induced in astrocytes. The excessive NO production that is associated with this isoform may contribute to the neurotoxicity of the retinal ganglion cells in eyes with chronic moderately elevated IOP.

Different responsiveness to nitric oxide-cyclic guanosine monophosphate pathway in cholinergic and tachykinergic contractions of the rabbit iris sphincter muscle.

PURPOSE: In the rabbit iris sphincter muscle, sodium nitroprusside (SNP), a nitric oxide (NO) donor, inhibits cholinergic contraction but does not affect tachykinergic contraction in vitro. The objectives of the current study were to clarify the mechanism for the different responsiveness to NO in cholinergic and tachykinergic muscular contractions, and to examine whether the mechanism for NO-induced inhibition of cholinergic muscular contraction is operative in vivo. METHODS: Iris sphincter muscle was dissected from the rabbit eye pretreated with or without endotoxin (lipopolysaccharide, LPS) in vivo. Cyclic guanosine monophosphate (cGMP) content in the iris sphincter muscle was determined by radioimmunoassay. The motor activity of the ring-shaped iris sphincter muscle was measured isometrically. Sodium nitroprusside, carboxy-2-phenyl-4,4,5,5,-tetramethyl-imidazoline-1-oxyl-3-oxide (C-PTIO, a scavenger of NO radicals), and 8-bromo cGMP (a permeable cGMP analogue) were administered between the first and second administrations of carbachol and neurokinin A, both of which had caused sustained contraction in the iris sphincter muscle. RESULTS: Sodium nitroprusside inhibited the contraction of the iris sphincter muscle caused by carbachol but had no effect on the contraction caused by neurokinin A. Application of C-PTIO significantly reduced SNP-induced cGMP accumulation in the muscle, as well as the SNP-induced inhibition of muscular contraction caused by carbachol. Neither carbachol nor neurokinin A influenced SNP-induced cGMP accumulation in the muscle. Induction of 8-bromo-cGMP significantly diminished the muscular contraction caused by carbachol but not that caused by neurokinin A. In vivo pretreatment of the eye with LPS increased, in a time-dependent manner, the cGMP accumulation in the iris sphincter muscle, which was significantly inhibited by pretreatment of NG-nitro-L-arginine methyl ester (an inhibitor of NO synthesis) in vivo. CONCLUSIONS: These results demonstrate that in rabbits the increase in cGMP accumulation induced by NO in the iris sphincter muscle is involved in the cholinergic contraction but not in the tachykinergic contraction, suggesting that different sensitivities to cGMP are essential for the different responsiveness to NO. Furthermore, the results of this study showed that the NO-cGMP pathway is operative in vivo and regulates iris sphincter muscle tone, at least when the eyes are infected with bacteria.

Nitric oxide-sensitive and -insensitive contractions of the isolated rabbit iris sphincter muscle.

PURPOSE: The rabbit iris sphincter muscle is innervated by cholinergic and tachykinergic nerves that regulate its tone. To clarify the involvement of nitric oxide (NO) in the postsynaptic regulation of the rabbit iris sphincter muscle tone, the authors examined the effects of NO-related agents on the cholinergic contraction induced by carbamylcholine (carbachol) and the tachykinergic contraction induced by neurokinin A. METHODS: The motor activity of the ring-shaped rabbit iris sphincter muscle was measured isometrically. Sodium nitroprusside (SNP, a NO donor) was administered between the first and second administrations of carbachol and neurokinin A, each of which induced sustained contraction. The effects of carboxy-2-phenyl-4,4,5,5,-tetramethyl-imidazoline-l-oxyl-3-oxide (carboxy-PTIO, a scavenger of NO radicals), NG-monomethyl-L-arginine (L-NAME, an inhibitor of NO formation from L-arginine), and methylene blue (an inhibitor of soluble guanylate cyclase) on contractions induced by carbachol and neurokinin A also were studied. Cyclic guanosine monophosphate (GMP) content in the muscle was determined by radioimmunoassay. RESULTS: Sodium nitroprusside inhibited carbachol-induced contractions of the iris sphincter muscle in a concentration-dependent manner but had no effect on neurokinin A-induced muscle contractions. Carboxy-PTIO and methylene blue significantly diminished the inhibitory effect of SNP on carbachol-induced contractions. L-NAME had no effect on contractions induced by either carbachol or neurokinin A. Sodium nitroprusside alone increased cyclic GMP accumulation in a concentration-dependent manner. CONCLUSIONS: This study showed that SNP inhibited cholinergic contractions mainly through a cyclic GMP-dependent mechanism but did not affect the tachykinergic contractions, indicating that cholinergic contraction is NO sensitive, whereas tachykinergic contraction is NO insensitive. These findings suggest that in rabbits, the cholinergic and tachykinergic responses have distinct features for the fine adjustment of the iris sphincter muscle tone.

Enhancement by cyclosporine A and tacrolimus of serotonin-induced formation of small platelet aggregation.

Cyclosporine A (CsA) may increase the incidence of thrombotic events, but whether tacrolimus (Tc) has such effects is still unclear. The serotonergic system has been linked to the thrombotic effects of CsA, but a direct effect of CsA on serotonin-induced platelet aggregation has not been demonstrated because of methodological difficulties. We measured the effects of CsA and Tc on serotonin-induced platelet aggregate formation by particle counting using light scattering. CsA and Tc both enhanced serotonin-induced formation of small platelet aggregates, however, neither CsA nor Tc affected aggregation induced by high or low concentrations of ADP, with or without addition of a serotonin receptor antagonist. Both CsA and Tc enhance platelet aggregation induced via the serotonin pathway.

Juvenile myelomonocytic leukemia relapsing after allogeneic bone marrow transplantation successfully treated with interferon-alpha.

We report a 5-year-old boy with juvenile myelomonocytic leukemia (JMML) which relapsed after an allogeneic bone marrow transplant who was successfully treated with interferon-alpha (IFN-alpha). One year after starting the therapy, he remains clinically well and in complete remission while continuing treatment with IFN-alpha and bestatin. Although the precise mechanism by which remission was induced is uncertain, a GVL effect combined with a direct antileukemia effect of IFN-alpha may be responsible. Further assessment of the role of IFN-alpha in relapsed JMLL patients is warranted.

Ganciclovir is effective for prophylaxis and treatment of human herpesvirus-6 in allogeneic stem cell transplantation.

Human herpesvirus 6 (HHV-6) infection and disease are serious complications of allogeneic hematopoietic stem cell transplantation (allo-SCT). Ganciclovir (GCV) is effective against HHV-6 in vitro but the antiviral susceptibility of HHV-6 has not been well characterized in vivo. We retrospectively compared the HHV-6 reactivation rate in pediatric allo-SCT recipients with and without GCV prophylaxis. The HHV-6 reactivation rate at 3 weeks after allo-SCT in patients without prophylactic GCV administration was significantly higher than that in those receiving prophylactic GCV (11/28 vs 0/13, P < 0.01). Five of 36 patients without prophylactic GCV showed clinical manifestations including skin rash, interstitial pneumonitis, persistent thrombocytopenia, enterocolitis and thrombotic microangiopathy, respectively. HHV-6-associated symptoms were observed in one of the 13 patients receiving prophylactic GCV. This patient showed fever, diarrhea and graft rejection concomitantly with a sudden increase of HHV-6 DNA copy number. Patients who received GCV for treatment of HHV-6 infection showed an improvement in symptoms and/or decrease of HHV-6 copy number. Thus, GCV is effective for treating HHV-6 disease after allo-SCT in vivo.

Foscarnet therapy for ganciclovir-resistant cytomegalovirus retinitis after stem cell transplantation: effective monitoring of CMV infection by quantitative analysis of CMV mRNA.

We report three pediatric patients with ganciclovir-resistant cytomegalovirus (CMV) retinitis who were successfully treated with foscarnet. The patients were recipients of hematopoietic stem cell transplantation (SCT) from HLA-mismatched donors. Because these patients had developed or experienced progressive CMV retinitis during ganciclovir therapy, they received foscarnet therapy at 60 mg/kg every 8 h. Their retinitis resolved promptly after initiating foscarnet therapy, suggesting foscarnet's effectiveness in treating ganciclovir-resistant CMV infection. The amount of CMV mRNA was quantitatively measured using an NASBA technique, which amplified the beta2.7 transcripts specific for CMV replication. This technique was useful for monitoring disease activity in a more rapid and sensitive manner than the PCR assay for CMV DNA.

Peripheral blood stem cell autografts for the treatment of children over 1 year old with stage IV neuroblastoma: a long-term follow-up.

This is the first report of the long-term therapeutic results in 22 children more than 1 year old with stage IV neuroblastoma who were treated with autologous peripheral blood stem cell transplantation (PBSCT). The median age of the patients at PBSCT was 4 years (1 to 10 years) and seven of the 17 patients who were evaluated for N-myc amplification were positive. PBSC were collected by a median of four aphereses per patient. The patients underwent PBSCT from 6 to 21 months after the start of therapy (median 10.5 months) at which time 13 patients were in CR, seven were in PR, and two had refractory disease. Multi-drug therapy using the 'high-MEC' regimen consisting of carboplatinum (400 mg/m2) and VP-16 (200 mg/m2) on days -7 to -4, and melphalan (90 mg/m2) on days -3 and -2, was the primary cytoreductive regimen. The median number of infused MNC and CFU-GM was, respectively, 4.3 x 10(8)/kg and 2.4 x 10(5)/kg. After PBSCT, three patients died of regimen-related toxicities and one patient who was transplanted with refractory disease died of disease progression without any benefit from transplantation. Hematological recovery was evaluated in 21 patients, excluding one early death. The median number of days required to achieve an AGC of >0.5 x 10(9)/l and platelet count of >50 x 10(9)/l were, respectively, 11 and 46. Eleven patients relapsed 3 to 50 months after PBSCT, and currently seven patients (5/13 who were transplanted in CR and 2/7 in PR) are surviving disease-free at 52 to 84 months. Although the retrospective nature of this study and several variables prevent a meaningful analysis, the overall results still support the feasibility of developing a prospective study of PBSCT with a larger number of children with high-risk neuroblastoma.

Atypical nerve fiber layer defects in high myopes with high-tension glaucoma.

The incidence of atypical optic nerve head and retinal nerve fiber layer defects was studied in 61 high myopic eyes (greater than or equal to -5 diopters) and 91 emmetropic or hyperopic eyes (0 to +3 diopters) of 152 patients with chronic high-tension glaucoma, and in 45 control myopic eyes (greater than or equal to -5 diopters). Horizontal ovalness or cyclotorsion, oblique insertion of the optic disc, and bean pot disc were more common in the high myopes. In the eyes with high myopia with glaucoma, inferior dominant nerve fiber layer defects, ectopic fiber defects, and multiple nerve fiber layer defects were common. The incidence of superior nerve fiber layer defects or superior-inferior equal nerve fiber layer defects was high in round or vertically oval discs and low in cyclotorted or horizontal oval discs. The oblique insertion of the discs correlated positively with a higher incidence of ectopic defects in high myopic eyes with glaucoma. The incidence of focal type nerve defects is higher in older patients and high myopes with oblique insertion of the optic disc. Atypical shape of the optic disc correlates positively with atypical retinal nerve fiber layer defects in eyes with high-tension glaucoma.