Longitudinal analysis of the peripapillary retinal nerve fiber layer thinning in patients with retinitis pigmentosa.

PURPOSE: To investigate longitudinal changes in peripapillary retinal nerve fiber layer (RNFL) thickness in patients with retinitis pigmentosa (RP). METHODS: We re-examined 103 RP patients whose RNFL thickness was previously examined and reported. RNFL thickness was measured using Stratus optical coherence tomography and was compared with the previous measurements. The results were also compared with that of previously reported normal subjects. Association between the decrease rate and visual acuity, and visual field was also investigated. RESULTS: The mean follow-up period was 56.9 months. After excluding the patients in whom RNFL images were of poor quality, 88 patients were eventually analyzed. The average RNFL thickness decreased from 105.8 to 98.2 µm during the period, with the average rate of decrease being 1.6 µm/year. The decrease in RNFL was more evident in superior and inferior sectors. Cross-sectional linear regression analysis also revealed an age-dependent decrease in RNFL, with the slower rate of decrease being 0.94 µm/year. The decrease in RNFL thickness was significantly faster than that reported in normal subjects. The decrease rate was not associated with visual functions. CONCLUSION: Age-dependent RNFL thinning occurs at a faster rate in RP patients as compared with that in normal subjects. The result supports the notion that pathologic changes involve inner retina as well as outer retina in eyes with RP. Considering the discrepancy in the rate of RNFL thinning estimated from trend analysis and longitudinal measurement, care should be taken when interpreting the result of cross-sectional analysis.

Left atrial appendage dysfunction in chronic nonvalvular atrial fibrillation is significantly associated with an elevated level of brain natriuretic peptide and a prothrombotic state.

The study tested the hypothesis that left atrial appendage (LAA) dysfunction in nonvalvular atrial fibrillation (NVAF) correlates with a prothrombotic state, and investigated whether the plasma natriuretic peptides are marker of LAA dysfunction in NVAF. Sixty-seven patients underwent transthoracic and transesophageal echocardiography. The left ventricular fractional shortening, left atrial diameter (LAD), LAA flow velocity and the grade of spontaneous echo contrast (SEC) were determined. The plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), D-dimer, and thrombin-antithrombin III complex (TAT) were measured. The patients were divided into 2 groups according to LAA flow velocity: group I (LAA velocity <20 cm/s) and group II (LAA velocity > or = 20cm/s). The SEC score, D-dimer, TAT, BNP and LAD were significantly increased in group I. Based on simple linear regression analysis, SEC score (r=-0.638), LAD (r=-0.493), D-dimer (r = -0.485), BNP (r = -0.463), TAT (r = -0.455) and age (r = -0.314) were inversely correlated with LAA flow velocity. Multivariate analysis showed that SEC score (p = 0.0014) and plasma BNP level (p=0.0075) were independent negative predictors for LAA flow velocity. In conclusion, LAA dysfunction is associated with a prothrombotic state, and the plasma BNP concentration may serve as a determinant of LAA function in NVAF.

Auditory brainstem response and temporal bone pathology findings in a brain-dead infant.

The criteria for assessing adult brain death have been already established, but those for infant brain death have not been yet established in Japan. We report auditory brainstem response (ABR) and postmortem pathology of the temporal bone and brain of a brain-dead 9-month-old female. During the comatose state, her ABR showed only waves I and II bilaterally. Autopsy revealed the presence of a left cerebellar astrocytoma, herniation and anoxic encephalopathy. The pathological examination of the temporal bone revealed the destruction of the inner ear particularly on the left side. In the auditory pathway of brain-dead patients, degeneration occurs first in the cerebrum, followed by the cochlear nerve. Thus, ABR is one of the useful means to assess brain death even in infants.

Endothelin-1 is involved in the growth promotion of vascular smooth muscle cells by hyaluronic acid.

Proliferation of vascular smooth muscle cells (VSMC) is crucial to the progression of arteriosclerosis. In this study, we examined the role that interactions among endothelin-1 (ET-1), CD44, and hyaluronic acid (HA) play in VSMC proliferation. Co-localization of ET-1, CD44 and HA positive areas, as well as proliferating cell nuclear antigen positive nuclei, were observed in mouse neointima induced by endothelial injury. As found in intimal VSMC, cultured mouse VSMC secreted ET-1. The endothelin-converting enzyme (ECE) inhibitor, phosphoramidon, and endothelin type-A (ETA) receptor antagonist BQ-123 reduced expression of CD44 in VSMC. ET-1 reversed the reduction of CD44 expression by phosphoramidon. Because CD44 is a receptor for HA, we investigated the effects of phosphoramidon, BQ-123 or ET-1 on the mitogenic activity of HA in VSMC. Among the different molecular weights of this polysaccharide, oligosaccharides of HA (oHA) stimulated VSMC proliferation most effectively. Phosphoramidon and BQ-123 inhibited this oHA-induced DNA synthesis in VSMC. ET-1 reversed the suppression of oHA-induced proliferation by phosphoramidon. In conclusion, endogenously secreted ET-1 enhances oHA-stimulated VSMC growth via the ETA receptor in an autocrine manner. Thus it is suggested that the CD44-inducing activity of ET-1 is responsible for its stimulating effect on oHA-dependent growth of VSMC. These findings support the hypothesis that the interactions among ET-1, CD44 and HA promote the progression of arteriosclerosis.

[Myeloperoxidase-antineutrophil cytoplasmic antibody positive alveolar hemorrhage during propylthiouracil therapy for hyperthyroidism].

A 62-year-old woman had been treated with propylthiouracil(PTU) for hyperthyroidism. Because bloody sputum, dyspnea, and severe hypoxemia developed, the patient was admitted to our hospital. Chest X-ray and chest computed tomographic (CT) films disclosed diffuse infiltrative shadows in both lung fields. Bronchoalveolar lavage revealed abundant hemosiderin-laden macrophages. Alveolar hemorrhage associated with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) positive vasculitis syndrome was diagnosed because of the high serum level of MPO-ANCA. After the initiation of steroid therapy and termination of PTU, the infiltrative shadows in both lung fields disappeared, PaO2 improved, and MPO-ANCA decreased. There have been some reports of MPO-ANCA positive vasculitis syndrome developing during PTU therapy, but most were concerned with renal disease. We concluded that PTU and similar agents should be given consideration as one of the possible causes of MPO-ANCA-induced alveolar hemorrhage.

Fluctuating gene expression and localized cellular distribution of vasoactive intestinal contractor (VIC) in mouse uterus.

To understand the physiological roles of vasoactive intestinal contractor (VIC) and endothelin-2 (ET-2) in the uterus, we examined the expression levels of VIC mRNA by real-time quantitative reverse transcription-linked polymerase chain reaction (RT-PCR) and characterized the cellular distribution of VIC peptide and mRNA by immunostaining and in situ hybridization in mouse uterus. In pregnant mouse uterus, VIC mRNA expression changed considerably between Days 10.5 and 12.5 of pregnancy. The expression levels were significantly (p<0.05) higher (approximately fivefold) in the later stage of pregnancy (Days 12.5-17.5) than in the earlier stage (Days 7.5-10.5). In nonpregnant uterus, VIC mRNA expression was significantly (p <0.05) higher (approximately threefold) in proestrus and estrus than in diestrus. Immunohistochemical studies demonstrated the presence of VIC peptide in endometrial epithelial cells, myometrial cells, and vascular smooth muscle cells during the estrous cycle and pregnancy and after parturition. Notably, myometrial cells showed dominant immunostaining in proestrus and estrus, in the later pregnancy stage, and in the early postpartum period, analogous to the expression pattern of VIC mRNA. In situ hybridization confirmed localization of VIC mRNA in myometrial cells. These findings suggest that VIC may play an important role in the function of myometrial cells.

Hydrocephalus in the Otx2+/- mutant mouse.

Mice with the Otx2+/- mutation often die during the postneonatal period. Before death these animals, generated from TT2 ES cells and crossed with CBA mice, develop a dome-shaped head, weakness of the limbs, kyphosis, lethargy, drowsiness, and emaciation. Autopsy of these mice revealed eminent dilatation of lateral ventricles and a ballooned cerebrum. Histological analysis shows edematous change of the periventricular white matter. These results suggest that Otx2 functions as a head organizer, and a mutation of this gene is a likely cause of hydrocephalus in mammals. Additionally, craniobasal skeletal anomaly in half of the heterozygotes and dwarfism in some of the female heterozygotes are described.

Metachronous ovarian dysgerminoma after a suprasellar germ-cell tumor treated by radiation therapy. Case report.

A case of suprasellar germ-cell tumor in a 9-year-old girl who later developed ovarian dysgerminoma is reported. The clinical course of the case is described and a double-primary tumor, rather than metastasis from either tumor to the other, is suggested by the authors to explain the oncogenesis in this patient. The authors strongly encourage that patients with intracranial germinoma be examined for associated extraneural lesions before, as well as after, the completion of the initial therapy.

Massive intracerebral hematoma in a child with Klippel-Trenaunay syndrome.

The authors describe a child who suffered from massive intracerebral bleeding due to rupture of a cerebral arteriovenous malformation associated with Klippel-Trenaunay syndrome (KTS). Neurovascular lesions have been regarded as uncommon in KTS; however, our case may indicate the need for neurovascular scrutiny in patients with this syndrome.

[A case of unilateral gustatory disturbance produced by the contralateral midbrain lesion].

We reported a case of unilateral gustatory disturbance produced by a lesion in the contralateral midbrain. A 37-year-old man first noticed dysesthesia in the left side of his face. Later, the patient developed dysesthesia of the left part of the lip, muscular weakness on the left lower extremity and gustatory disturbance on the left side. MR scan disclosed a lesion in the tegmentum of the right midbrain, which showed low intensity on a T1-weighted image and high intensity on a T2-weighted image. This lesion could be due to multiple sclerosis. This case suggests that the unilateral gustatory information ascends via the contralateral pathway at the midbrain level. It is suggested that the central gustatory pathways above the ipsilateral pontine taste are ascend via the contralateral projections to the thalamic taste area (parvicellular portion of the ventral posteromedial thalamic nucleus, VPMpc).

Magnetic resonance angiography in the management of childhood moyamoya disease: first choice for neurovascular scrutiny.

We performed magnetic resonance angiography (MRA) in 12 children with a suspected or angiographically proven moyamoya disease. MRA was performed by the three-dimensional, time-of-flight technique and, successfully depicted the primary abnormalities in the distal carotid arteries in 10 out of the 12 patients. In the other two patients, poor visualization of the intracranial vasculature strongly suggested the presence of the disease. On MRA, moyamoya vessels were visible in eight patients. The presence of anastomoses was also confirmed by MRA in seven of the 10 patients who had undergone encephalo-duro-arterio-synangiosis. Our findings suggest that MRA may be the tool of choice for selecting patients to undergo conventional angiography. However, establishing a definite diagnosis still requires some improvements in the delineation of the fine vasculature.

Primary ocular and central nervous system malignant lymphoma first manifested as uveitis: possible role of single photon emission computed tomography with N-isopropyl-123I-p-iodoamphetamine in the diagnostic procedure.

A case of primary ocular and central nervous system malignant lymphoma was reported which was first manifested as bilateral uveitis ten months before the neurological symptoms appeared. The lesion of lymphoma in the central nervous system was clearly demonstrated as a heavy accumulation of N-isopropyl-123I-p-iodoamphetamine by single photon emission computed tomography. Since most brain tumors reportedly show a low uptake of N-isopropyl-123I-p-iodoamphetamine, single photon emission computed tomography with N-isopropyl-123I-p-iodoamphetamine could be helpful in making the diagnosis, as well as in visualizing primary central nervous system malignant lymphoma.

Dynamic changes in cytochrome oxidase activity in the rat somatosensory cortex following thalamocortical deafferentation.

The changes in cytochrome oxidase (CYO) activity in the primary somatosensory cortex (SI) induced by unilateral lesions restricted to the posterior ventrobasal region of the thalamus were investigated by histochemical techniques and photometric semi-quantitation in the rat. The CYO activity decreased rapidly and dramatically in layer IV of the lesioned side, reaching its lowest level within 2 weeks, and remained depressed at 8 weeks post-lesion. Segmentations normally seen in layer IV corresponding to barrels remained absent. While less marked decreases were also noted in other layers, obvious recovery was subsequently observed, attaining levels comparable to those on the intact size at 6 or 8 weeks post-lesion. The persistent decrease in layer IV appears to reflect a reduced thalamocortical activation of the dendritic profiles and neuronal perikarya. The recovery in other layers may represent an increase in the resting level of the initially depressed neuronal activity near to the original levels. The persistent reduction of function in the inhibitory surround, which is normally activated by thalamocortical input, may contribute to the increase in CYO activity.

[Multiple giant aneurysm--a case report].

We report a case of five aneurysms, including three giant aneurysms, a pair of symmetric aneurysms, and two fusiform aneurysms. The initial clinical symptom was a cerebral ischemic attack. On admission, the patient complained of sudden onset of speech disturbance. Physical examination showed left hemiparesis. Radiological studies, including computed tomography and cerebral arteriography, revealed multiple low density areas bilaterally in the basal ganglia and three fusiform giant aneurysms bilaterally in the middle cerebral arteries and basilar artery. Considering the difficulty of surgical treatment, the patient was discharged. Six months later, complaining of right hemiparesis and total dysphasia, the patient was readmitted to our department. CT scan on admission revealed no changes except for ischemic changes. During the second admission, another attack of subarachnoidal hemorrhage due to rupture of the left middle cerebral artery aneurysm occurred, and the patient died. Autopsy was performed, and two more aneurysms, not visualized in the former studies, were found in the right anterior communicating artery and the cortical branch of the right middle cerebral artery. The occurrence of aneurysms in such a fashion as seen in the present case is to be very rare in the aspect of the size, the multiplicity and the bilaterally development.

Neuro-otological study of positional vertigo caused by head injury.

A neuro-otological examination was given to 22 patients with paroxysmal positional vertigo within 1 week of head injury. In all cases, reverse rotatory positional nystagmus accompanied by a vertiginous sensation was observed in the positional nystagmus test. No relationship between the affected side and the direction of eye movement in the head-hanging position was found in the positional nystagmus test. From the prognosis and the nystagmus findings, the cause of the vertigo was thought to be partial damage to the inner ear. The clinical course was generally favorable, but recovery was slower in the 11 cases with neuro-otologically demonstrated central nervous system disorders than in the other 11 cases.

Scanning electron microscopic studies of the membranous labyrinth after transtympanic infusion of local anesthetics (lidocain).

Scanning electron microscopic observation of the transtympanic infusion of 10% xylocain revealed twisting and disorders of outer hairs especially from the 2nd and 3rd rows of the basal to the 2nd turn of the organ of Corti, and adhesion and fusion of the sensory hairs of the crista ampullaris and otolith organ 1 and 4 days after injection. Four percent xylocain however demonstrated very minor alteration of the sensory hairs and no missing sensory hairs were detected from any cases. The authors hypothesized from electron microscopic observation that adhesion and fusion of vestibular sensory hairs or twisting and disorders of the sensory hairs of the organ of Corti might act to intercept harmful circulation of exclusion of abnormal excitement of hair cells and the innovation of electrical discharge of sensory hairs due not only to the pharmacological effects of xylocain but also to osmotic pressure.