Antagonistic effects of two herbs in Zuojin Wan, a traditional Chinese medicine formula, on catecholamine secretion in bovine adrenal medullary cells.

In order to research the target of superior efficacy and lesser side effects, combination of herbal materials has been applied to phytotherapy for thousands of years in China and some other countries. Zuojin Wan (ZJW), a famous traditional Chinese medicine formula, is used in treating gastric diseases in China. It is composed of two herbs, Rhizoma Coptidis (RC) and Fructus Evodiae (FE) in the ratio of 6: 1(w/w). In the present study, we examined the effects of ZJW, RC, FE and active components isolated from these herbs on catecholamine (CA) secretion and intracellular calcium ([Ca(2+)](i)) in cultured bovine adrenal medullary cells. Extracts of ZJW and RC and berberine, palmatine and jatrorrhizine, components of RC, all inhibited CA secretion and rise in [Ca(2+)](i) induced by acetylcholine (ACh), veratridine (Ver) and/or 56 mM K(+). On the other hand, extract of FE, evodiamine and rutaecarpine, components of FE, stimulated CA secretion and rise in [Ca(2+)](i) induced by ACh. Furthermore, different proportions of RC and FE caused different responses in CA secretion. The present findings suggest that two herbs in ZJW have opposite effects, i.e., inhibitory effect of RC and stimulatory effect of FE, on CA secretion induced by acetylcholine in cultured bovine adrenal medullary cells.

Value of digital volume tomography in patients with conductive hearing loss.

Digital volume tomography (DVT) is an extension of panoramic tomography. With this diagnostic technique, characterized by high resolution, a narrow section width (0.125 mm) and three-dimensional display, small pathological processes can be well visualized. Twenty-five patients with the history of a progressive hearing loss were examined with DVT (Accu-I-tomo, Morita, Japan). The results were compared with pre- and intraoperative findings to evaluate the diagnostic value of DVT in cases of erosion of the ossicular chain. With high resolution and artifact-free demonstration of the middle ear and the ossicular chain, it was possible to define its continuity preoperatively by DVT in all 25 cases. An intact ossicular chain was found by DVT in 13 cases and was later confirmed by surgery. The predicted erosion of the ossicles was verified in 12 patients, and a tympanoplasty type III was performed. Digital volume tomography is an excellent technique to examine the middle ear cleft and inner ear, and expands the application of diagnostic possibilities in the lateral skull base. Therefore, improvement in preoperative diagnosis is achieved along with more accurate planning of the surgical procedure. Digital volume tomography delivers a small radiation dose with a high resolution and a low purchase price for the equipment.

Mechanisms of cytosolic Ca2+ suppression by prostaglandin E2 receptors in rat melanotrophs.

We have previously reported that voltage-dependent Ca2+ (VDC) channels of rat melanotrophs are inhibited by prostaglandin E2 (PGE2). In this study, mechanisms involved in the inhibitory actions of PGE2 receptors of rat melanotrophs were analysed using reverse transcriptase-polymerase chain reaction (RT-PCR), Ca2+-imaging and whole-cell, patch-clamp techniques with recently developed EP agonists, each of which is selective for the known four subclasses of EP receptors (EP1-4). PGE2 reversibly suppressed the cytosolic Ca2+ concentration ([Ca2+]i). The maximum reduction in [Ca2+]i by PGE2 was comparable to that by dopamine or to that by extracellular Ca2+ removal. RT-PCR analysis of all four EP receptors revealed that EP3 and EP4 receptor mRNAs were expressed in the intermediate lobe. The effects of PGE2 to suppress [Ca2+]i were mimicked by the selective EP3 agonist, ONO-AE-248, whereas three other EP agonists, ONO-DI-004 (EP1), ONO-AE1-259 (EP2) and ONO-AE1-329 (EP4), had little or no effect on [Ca2+]i. All four G-protein activated inward rectifying K+ (GIRK) channel mRNAs were identified in intermediate lobe tissues by RT-PCR. Dopamine concentration-dependently activated GIRK currents, whereas PGE2 did not activate GIRK currents, even at the concentration causing maximal inhibition of VDC channels. These results suggest that PGE2 acts on EP3 receptors to suppress Ca2+ entry of rat melanotrophs by selectively inhibiting VDC channels of these cells. We have compared the possible cellular and molecular mechanisms of inhibition by dopamine and PGE2.

Ultrasound biomicroscopic study of ciliary body changes in the post-treatment phase of Vogt-Koyanagi-Harada disease.

AIMS: To investigate the usefulness of ultrasound biomicroscopy for evaluating changes in the ciliary body in patients with Vogt-Koyanagi-Harada disease. METHODS: Ultrasound biomicroscopy was used to evaluate 14 eyes of seven patients diagnosed with Vogt-Koyanagi-Harada disease. Cross sectional images of the ciliary body and thickness of the pars plana 3.0 mm posterior to the scleral spur were examined. Predicted thickness of the pars plana was obtained by multiple linear regression analysis of thickness in the acute phase and in the remission phase. RESULTS: In the active phase, the cross sectional images showed a shallow anterior chamber in eight of the 14 eyes, ciliochoroidal detachment in five eyes, and a thickened ciliary body in all 14 eyes. Internal reflectivity of the ciliary stroma was low, with ciliary processes being unclear in 13 eyes. One month after steroid treatment, slit lamp examination findings were normal in 14 eyes. 10 eyes of five patients were examined by ultrasound biomicroscopy at this stage. Ciliochoroidal detachment was no longer seen in any eye. Internal reflection of the ciliary stroma became relatively homogeneous, and the ciliary processes were seen, though not clearly. However, the pars plana remained thickened. The actual thickness was greater at 1 month after steroid treatment than the predicted thickness for the remission phase. In the remission phase, the internal reflection was homogeneous and the ciliary processes were delineated clearly in all 14 eyes. CONCLUSION: Objective, quantitative evaluation of the ciliary body is possible with ultrasound biomicroscopy during the course of Vogt-Koyanagi-Harada disease. Ultrasound biomicroscopy is useful in determining disease activity in the anterior segment and in monitoring the clinical course, and it may improve evaluation of the efficacy of treatment.

Production of cAMP by adrenomedullin in human oligodendroglial cell line KG1C: comparison with calcitonin gene-related peptide and amylin.

The actions and the presence of adrenomedullin (AM) were investigated in cultured human oligodendroglial cell line KG1C. AM and AM mRNA were detected in KG1C cells by immunohistochemistry and RT-PCR. mRNAs for calcitonin receptor-like receptor (CRLR) and receptor-activity-modifying proteins (RAMPs) 1, 2 and 3 but not for calcitonin receptors were detected in the cells, while mRNAs for CRLR, calcitonin receptors and all RAMPs were detected in the human cerebellum. Application of AM resulted in time- and concentration-dependent increases in the cAMP level of KG1C cells. Calcitonin gene-related peptide (CGRP) and amylin, peptides structurally related to AM, also increased cAMP. The potencies for the cAMP production of the three peptides were CGRP > or =AM >> amylin with EC(50) of 8, 18, 90 nM, respectively. The responses induced by AM were strongly inhibited by the CGRP(1) receptor antagonist human CGRP(8-37), and inhibited also by the AM receptor antagonist human AM(22-52). In contrast, the responses induced by CGRP or amylin were inhibited only by CGRP(8-37) and not by AM(22-52). The responses induced by all three peptides were unaffected by the amylin receptor antagonist human amylin(8-37). The CGRP(2) receptor agonist human [Cys(Acm)(2,7)]CGRP significantly increased the cAMP level but the increase was smaller than that caused by CGRP. This increase in cAMP was unaffected by CGRP(8-37), AM(22-52) or by amylin(8-37). These results suggest that in KG1C cells, AM increases cAMP through AM and CGRP(1) receptors, whereas CGRP does so through CGRP(1) and CGRP(2) receptors, and amylin exerts its effects through CGRP(1) receptors. Collectively, these findings imply that AM released from oligodendroglial cells may play a role in the regulation of oligodendrocytes via autocrine/paracrine through AM receptors and CGRP(1) receptors.

Hepatocyte growth factor promotes epithelial morphogenesis and occludin linkage to the cytoskeleton in cultured retinal pigment epithelial cells.

BACKGROUND: Although hepatocyte growth factor (HGF) is also known as scatter factor, it induces epithelial morphogenesis in cultured bovine retinal pigment epithelial (RPE) cells. To elucidate the mechanism of epithelial morphogenesis, we investigated the influence of HGF on occludin, a major component of tight junctions. METHODS: RPE cells were plated on collagen type 1-coated chamber slides or dishes, 20 ng/ml HGF was added and the cells were incubated for 1 week. Cells were harvested at several time-points, and occludin expression was examined by immunohistochemistry. Detergent extraction protocols to identify the intensity of occludin linkage to the cytoskeleton were also used. Occludin expression was determined semiquantitatively by Western blotting. RESULTS: Fluorescence microscopy revealed that HGF treatment increased the levels of insoluble occludin at the cell borders after detergent extraction. These level of insoluble occludin and the associated epithelial morphology were maintained for more than 3 weeks after withdrawal of HGF, whereas cells not treated with HGF had a fibroblastic appearance. Western blotting also showed that insoluble occludin was more abundant in HGF-treated cells. Furthermore, immunoreactive bands of insoluble occludin were somewhat larger than those of soluble occludin, suggesting that insoluble occludin may be modified in comparison to soluble occludin. CONCLUSION: Our results suggest that HGF promotes linkage of occludin to the cytoskeleton. HGF may become a therapeutic candidate in physiological recovery of RPE cells and in preparation of RPE monolayers for transplantation.

Inhibition by tramadol of muscarinic receptor-induced responses in cultured adrenal medullary cells and in Xenopus laevis oocytes expressing cloned M1 receptors.

Tramadol is a widely used, centrally acting analgesic, but its mechanisms of action are not completely understood. Muscarinic receptors are known to be involved in neuronal function in the brain and autonomic nervous system, and much attention has been paid to these receptors as targets of analgesic drugs in the central nervous system. This study investigated the effects of tramadol on muscarinic receptors by using two different systems, i.e., a Xenopus laevis oocyte expression system and cultured bovine adrenal medullary cells. Tramadol (10 nM-100 microM) inhibited acetylcholine-induced currents in oocytes expressing the M1 receptor. Although GF109203X, a protein kinase C inhibitor, increased the basal current, it had little effect on the inhibition of acetylcholine-induced currents by tramadol. On the other hand, tramadol did not inhibit the current induced by AlF4-, a direct activator of GTP-binding protein. In cultured bovine adrenal medullary cells, tramadol (100 nM-100 microM) suppressed muscarine-induced cyclic GMP accumulation. Moreover, tramadol inhibited the specific binding of [3H]quinuclidinyl benzilate (QNB). Scatchard analysis showed that tramadol increases the apparent dissociation constant (Kd) value without changing the maximal binding (Bmax), indicating competitive inhibition. These findings suggest that tramadol at clinically relevant concentrations inhibits muscarinic receptor function via QNB-binding sites. This may explain the neuronal function and anticholinergic effect of tramadol.

Indocyanine green angiograms of choroidal nevi. comparison between confocal and nonconfocal scanning laser ophthalmoscope and fundus video camera.

PURPOSE: A fundus video camera and a nonconfocal scanning laser ophthalmoscope (SLO) detect direct light and indirect light, whereas a confocal SLO detects mostly direct light. Differences in confocal and nonconfocal SLO images and fundus video camera images are most likely due to their different optical systems. These differences were examined in indocyanine green (ICG) angiograms of a choroidal nevus. METHODS: A confocal SLO, a nonconfocal SLO, and a high resolution digital fundus video camera were used to obtain ICG angiograms of pigmented choroidal nevi in 4 patients for 30 minutes following dye injection. RESULTS: All the angiograms showed a hypofluorescent region in the nevus until 10-14 minutes after dye injection, except in 1 patient in whom no hypofluorescent region was seen in an early confocal-SLO angiogram. From 20 minutes to 30 minutes postinjection, the hypofluorescent regions were still visible in all fundus video camera angiograms and nonconfocal SLO angiograms but not in confocal SLO angiograms. CONCLUSIONS: Early angiograms taken with the three angiography systems showed a similar appearance of the choroidal nevus. However, late ICG angiograms with a confocal SLO showed different images from those taken with a nonconfocal SLO or a fundus video camera. It is suggested that the angiography system and the aperture size of an SLO should be selected according to the aspect of the pigmented choroidal nevus that is of interest in late-phase ICG angiography.

Does ascorbic acid prevent retinopathy during interferon therapy in patients with chronic hepatitis C?

PURPOSE: Ascorbic acid was administered to patients with chronic hepatitis C to elucidate the mechanism of onset of retinopathy during interferon (IFN) therapy, and its prevention. METHODS: The subjects were 62 patients with chronic hepatitis C who had been admitted to our hospital. For the IFN therapy, 6 MIU of natural IFN-alpha, or 10 MIU of recombinant human IFN-alpha 2b was administered every day for the first 2 weeks, followed by administration three times a week for 22 weeks. The patients were randomly assigned to a group receiving 600 mg/day of ascorbic acid or a group not receiving ascorbic acid (control group). The optic fundi were examined by ophthalmologists before the IFN therapy began and subsequently at weeks 2 and 4 and then every 4 weeks during the IFN therapy. RESULTS: Retinopathy was found in 9 of the 31 patients (29%) in the ascorbic acid-treated group and in 11 of the 31 patients (35%) in the control group. The cumulative incidence of hemorrhage in the ascorbic acid-treated group was lower than that in the control group during the IFN therapy, but the difference between the two groups was not significant (P = 0.186). The cumulative incidence of cotton-wool spots in the ascorbic acid-treated group was almost same as that in the control group during the IFN therapy. The median platelet counts before the therapy was begun were 11.8 x 10(4)/mm2 in the group with hemorrhage and 16.6 x 10(4)/mm2 in the group without, and the lowest platelet counts during IFN therapy were 7.3 x 10(4)/mm3 in the group with hemorrhage and 9.5 x 10(4)/mm3 in the group without, indicating significantly lower values in the group with hemorrhage (P = 0.018 and P = 0.020, respectively). The lowest platelet counts during IFN therapy were 7.4 x 10(4)/mm3 in the group with cotton-wool spots and 9.7 x 10(4)/mm3 in the group without, indicating a significantly lower value in the group with cotton-wool spots (P = 0.036). CONCLUSIONS: Ascorbic acid was not considered to be useful for the prevention of the retinopathy associated with IFN therapy in patients with chronic hepatitis C.

New insulinomimetic zinc(II) complexes of alpha-amino acids and their derivatives with Zn(N2O2) coordination mode.

Zinc(II) complexes of alpha-amino acids and their derivatives with a Zn(N2O2) coordination mode were found to have in vitro insulinomimetic activity as estimated with the inhibition of free fatty acid release in isolated rat adipocytes treated with epinephrine. It was revealed that the insulinomimetic activities of zinc(II) complexes with over-all stability constants (log beta) less than 10.5 are higher than those of ZnSO4 and VOSO4. The high blood glucose level of KK-Ay mice with type 2 diabetes mellitus was lowered by daily intraperitoneal injections of a zinc(II) complex, cis-[Zn(L-Thr)2(H2O)2], for 14 d. The improvement of diabetes mellitus was confirmed with the oral glucose tolerance test.

Dual phases of functional change in norepinephrine transporter in cultured bovine adrenal medullary cells by long-term treatment with clozapine.

The effects of long-term treatment with clozapine, a prototype of atypical antipsychotic drugs, on the functional activity, synthesis and mRNA of norepinephrine (NE) transporter were examined in bovine adrenal medullary cells in culture. Treatment of cells with clozapine at 0.1-3.0 microM concentrations produced dual phases of changes in [(3)H]NE uptake, i.e. the first phase showed a decrease in [(3)H]NE uptake at 2-48 h, and the following phase showed an increase in uptake at 72-168 h. Treatment with clozapine for 6 h decreased V(max) to 40% of the control without changing the K(m) value for [(3)H]NE uptake. However, treatment with clozapine for 96 h increased V(max) by 56% over the control without a change in K(m). Scatchard plot analysis of [(3)H]desipramine (DMI) binding to membranes isolated from cells treated with clozapine for 6 h revealed a decrease in B(max) without any change in K(d); in contrast, treatment with clozapine for 96 h caused an increase in B(max) without any change in K(d). Both actinomycin D and cycloheximide, which are inhibitors of protein synthesis, suppressed the clozapine (96 h)-induced increase in [(3)H]NE uptake. Treatment of cells with clozapine for 12-96 h increased the level of NE transporter mRNA in a concentration-dependent manner (0.3-3.0 microM). These findings suggest that treatment of cells with clozapine results in the down-regulation and subsequent up-regulation of NE transporter. The latter change may be caused by the synthesis of new proteins of NE transporter via an increase in its mRNA.

Long-term results using a piezoelectric semi-implantable middle ear hearing device: the Rion Device E-type.

The Rion Device E-type (RDE) has been applied to 39 patients with severe mixed deafness that could not be rehabilitated by surgical means or the conventional hearing aid. Careful follow-up studies have been conducted on all of them to assess clinical and audiologic results. The device could function more than 10 years, affording natural quality of hearing without howling and wearing discomforts. Functional principles of the device, indications, and surgical methods of implantation are described. The failures and delayed problems were also presented together with the preventive measures.

Transmastoid decompression as a treatment of Bell palsy.

OBJECTIVE: We sought to assess the efficacy of transmastoid decompression after steroid treatment. STUDY DESIGN: One hundred one adults with Bell palsy having denervation exceeding 95% after steroid treatment were divided into 2 groups. In 58 patients decompression from the labyrinthine segment to the stylomastoid foramen was performed, and the remaining 43 patients were only followed up. Using the Yanagihara score and House Brackmann grading system, the recovery from the palsy was assessed. RESULTS: There was a statistically significant difference in the final facial score of the 2 groups. Within 60 days after the onset, the chance of better recovery from the palsy was higher in the patients with decompression. CONCLUSION: In the era of steroid treatment, we cannot discard the transmastoid decompression of the facial nerve in the treatment of severe Bell palsy with profound denervation, although further effort is needed to obtain definitive evidence to show the benefit of the operation.

Stimulation of catecholamine synthesis in cultured bovine adrenal medullary cells by leptin.

Recently, we characterized leptin receptors in bovine adrenal medullary cells (Yanagihara et al. 2000). Here we report the stimulatory effect of leptin on catecholamine synthesis in the cells. Incubating cells with leptin (10 nM) for 20 min increased the synthesis of 14C-catecholamines from [14C]tyrosine, but not from L-3,4-dihydroxyphenyl [3-14C]alanine. The stimulation of catecholamine synthesis in the cells by leptin was associated with the phosphorylation and activation of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine biosynthesis. The incubation of cells with leptin resulted in a rapid activation of the mitogen-activated protein kinases (MAPKs). An inhibitor of MAPK kinase, U0126, nullified the stimulatory effect of leptin on the synthesis of 14C-catecholamines. Leptin potentiated the stimulatory effect of acetylcholine on 14C-catecholamine synthesis, whereas leptin failed to enhance the phosphorylation and activation of tyrosine hydroxylase induced by acetylcholine. These findings suggest that leptin stimulates catecholamine synthesis via the activation of tyrosine hydroxylase by two different mechanisms, i.e., one is dependent on tyrosine hydroxylase phosphorylation mediated through the MAPK pathway and the second is independent of enzyme phosphorylation.

Fundus autofluorescence in patients with pseudoxanthoma elasticum.

PURPOSE: To characterize changes in fundus autofluorescence in patients with pseudoxanthoma elasticum (PXE). Fundus autofluorescence intrinsically derives from lipofuscin, and the degree of autofluorescence is thought to indicate the degree of retinal pigment epithelium (RPE) metabolic activity. METHODS: Twelve eyes of 6 patients (2 men, 4 women) with PXE were studied with a confocal scanning laser ophthalmoscope. Patient age ranged from 42 to 62 years. The autofluorescence of abnormal retinal areas was compared digitally with that of neighboring, presumed healthy control areas. When the average gray level of a fundus region was 2 SDs above or below the average gray level of a control area, autofluorescence of the fundus region was considered abnormal. RESULTS: In all 12 eyes, some segments of the angioid streaks showed decreased fundus autofluorescence, and other segments of the streaks showed normal autofluorescence. Areas of peripapillary chorioretinal atrophy seen in 2 eyes and of disciform scarring seen in 3 eyes showed decreased autofluorescence. Solitary or multiple drusen-like spots showed increased autofluorescence in all 12 eyes. CONCLUSION: Atrophic and degenerative RPE regions showed decreased fundus autofluorescence in areas of chorioretinal atrophy and in some segments of the angioid streaks. Some drusen-like spots showed increased autofluorescence. The characteristic changes in autofluorescence that we observed in PXE patients suggest that the content of the drusen-like substance differs from that of senile drusen and that the drusen-like lesions are similar to the sub-RPE deposits seen in macular dystrophy.

Dual effects of intravenous anesthetics on the function of norepinephrine transporters.

BACKGROUND: Norepinephrine transporters (NETs) terminate the neuronal transmission of norepinephrine, which is released from noradrenergic neurons. To investigate the interaction with NET, the authors examined the effects of short- and long-term treatment with anesthetics on the activity and mRNA level of NET. METHODS: To assay [3H]norepinephrine uptake, bovine adrenal medullary cells in culture were incubated with [3H]norepinephrine in the presence of intravenous anesthetics, including propofol, thiamylal, and diazepam. To study the direct interaction between the anesthetics and NET, the effect of propofol on the binding of [3H]desipramine to the plasma membrane was examined. To study the long-term effect of anesthetics, [3H]norepinephrine uptake by cells pretreated with propofol for 6-24 h and [3H]desipramine binding after pretreatment for 12 h were measured. Simultaneously, we examined the effect of anesthetics on the expression of NET mRNA using the reverse transcriptase-polymerase chain reaction. RESULTS: All of the intravenous anesthetics inhibited [3H]norepinephrine uptake in a concentration-dependent manner. The active concentrations of propofol (1-3 microm) and thiamylal (< or = 30 microm) were similar to those encountered clinically. The kinetic analysis revealed that all the anesthetics noncompetitively inhibited [3H]norepinephrine uptake. Propofol inhibited [3H]desipramine binding with a potency similar to that observed in [3H]norepinephrine uptake. Scatchard analysis showed that propofol competitively inhibited [3H]desipramine binding. On the other hand, long-term treatment of cells with propofol (10 microm) enhanced the NET functional activity and [3H]desipramine binding, and also increased the level of NET mRNA. CONCLUSIONS: These results suggest that intravenous anesthetics have a dual effect on NET; short-term treatment causes inhibition, whereas long-term treatment leads to up-regulation. The interaction of intravenous anesthetics with NET may modulate the neuronal transmission of norepinephrine during anesthesia.

Interleukin (IL)-4 and IL-13 inhibit the differentiation of murine osteoblastic MC3T3-E1 cells.

Interleukin-4 (IL-4) inhibits the spontaneous and stimulated bone resorption resulting from the inhibition of osteoclast formation, as well as osteoclastic activity. Since IL-13 shares some biological properties with IL-4, it was recently reported that IL-13 inhibits bone resorption. The present study was designed to determine the effects of murine IL-4 (IL-4) and murine IL-13 (IL-13) on the murine osteoblastic cell line MC3T3-E1. IL-4 and IL-13 stimulated 3H-thymidine incorporation in the MC3T3-E1 cells and its proliferation in dose dependent manners. A spontaneous increase in alkaline phosphatase (ALP) activity in the cells after plating was inhibited by IL-4 or IL-13, and both cytokines blunted an increase in ALP activity by human parathyroid hormone (PTH) (1-34). PTH-stimulated cyclic AMP (cAMP) production was inhibited by pretreatment with IL-4 and IL-13 for 48 hr in dose dependent manners. Pretreatment with IL-4 and IL-13 for 48 hr caused a decrease in PTH-induced cAMP production at any stimulatory concentration. However, the effective dose (ED50) was unchanged by the pretreatment with these cytokines. Pretreatment with IL-4 and IL-13 did not modulate cAMP generation by forskolin. In contrast, cAMP generation by PGE2 is greater in the cells treated with the cytokines compared to those without the cytokines. These results indicate that IL-4 and IL-13 act on MC3T3-E1 cells in the same manner, stimulating cell proliferation, but inhibiting cell differentiation. The inhibition of osteoblast differentiation by IL-4 and IL-13 may be associated with a decrease in PTH actions on osteoblasts.

Edematous swelling of the facial nerve in Bell's palsy.

Surgical decompression of the intratemporal facial nerve from the geniculate ganglion to the stylomastoid foramen was carried out in 91 patients with Bell's palsy. All of the patients had denervation exceeding 95%, and a suprastapedial lesion. Edematous swelling of the nerve was assessed using the following three grades: + +, nerve swells beyond the bony facial canal; +, nerve swells beyond the nerve sheath, but within the bony canal, and -, no notable swelling observed. Varying degrees of swelling of the nerve were noted in all of the patients from onset to the end of the ninth week. The incidence of + + swelling was highest within 3 weeks of onset and then declined. + + swelling was most often noted in the vicinity of the geniculate ganglion, and was thought to be a manifestation of inflammation due to herpes simplex virus infection. There was a clear time dependency of the swelling in the horizontal and pyramidal segments, but not in the mastoid segment. After the ninth week, the incidence of swelling decreased sharply and no swelling of the nerve was observed in about one-third of the patients. Considering the etiology and the analysis of edematous swelling, we propose that the course of Bell's palsy be differentiated into an acute phase (the first 3 weeks after onset), a subacute phase (from the fourth to ninth weeks) and a chronic phase (after the tenth week).

Ossiculoplasty using hydroxyapatite prostheses: long-term results.

The surgical results of ossicular chain reconstruction using a hydroxyapatite prosthesis were evaluated in 106 ears of 101 patients who were followed up for > 5 years. Successful reconstruction was defined as: (1) postoperative air-bone gap of