Conjoined lumbosacral nerve root: a case report.

BACKGROUND: In patients with conjoined nerve roots, hemilaminectomy with sufficient exposure of the intervertebral foramen or lateral recess is required to prevent destabilization and ensure correct mobility of the lumbosacral spine. To the best of our knowledge, no case reports have detailed the long-term course of conjoined nerve roots after surgery. CASE PRESENTATION: We report the case of a 51-year-old Japanese man with a conjoined nerve root. The main symptoms were acute low back pain, radiating pain, and right leg muscle weakness. Partial laminectomy was performed with adequate exposure to the conjoined nerve root. The symptoms completely resolved immediately after surgery. However, the same symptoms recurred 7 years postoperatively. The nerve root was compressed because of foraminal stenosis resulting from L5-S disc degeneration. L5-S transforaminal lumbar interbody fusion was performed on the contralateral side because of an immobile conjoined nerve root. At 44 months after the second surgery, the patient had no low back pain or radiating pain, and the muscle weakness in the right leg had improved. CONCLUSIONS: This is the first report of the long-term course of conjoined nerve root after partial laminectomy. When foraminal stenosis occurs after partial laminectomy, transforaminal lumbar interbody fusion from the contralateral side may be required because of an immobile conjoined nerve root.

Factors Associated with Intradiscal Vacuum Phenomenon after Traumatic Thoracolumbar Fracture.

Introduction Posttraumatic kyphosis of the thoracolumbar spine is a possible cause of deterioration of activities of daily living. Thus, postoperative kyphosis is an important issue in treating traumatic thoracolumbar fractures. The intradiscal vacuum phenomenon (IVP) after a traumatic thoracolumbar fracture is considered an important predictor of severe kyphosis after implant removal. However, the associated factors are not yet clear. Methods The study included data from 94 intervertebral discs on the cephalocaudal side of 47 fractured vertebrae of 45 patients for traumatic thoracolumbar fracture due to high-energy trauma. We assessed the demographics of patients (age, sex, cause of injury, location of injured vertebra, fracture type, cephalocaudal side), imaging finding (kyphosis angle of fractured vertebra at the injury, endplate fracture on computed tomography [CT], intervertebral injury on magnetic resonance image [MRI]), and IVP on CT conducted more than 6 months after surgery. We divided the intervertebral discs into an IVP group and a non-IVP group. To identify factors associated with an IVP, univariate analysis and multivariate logistic regression analysis were conducted. Results IVP was observed in 27 (29%) of 94 intervertebral discs on CTs conducted at an average of 14.0 months postoperatively. In univariate analysis, the IVP group ( n = 27) had a significantly more cephalic side of the injured vertebra, endplate fracture on CT, and disc injury on MRI compared with the non-IVP group ( n = 67). A multivariate logistic regression analysis was conducted to identify factors associated with IVP. The cephalic side (odds ratio [OR] = 4.183, 95% confidence interval [CI] = 1.269-13.785) and endplate fracture on CT (OR = 9.564, 95% CI = 1.940-47.143) were identified as independent factors associated with IVP. Conclusions IVP was observed in 27 (29%) of 94 intervertebral discs. The cephalic side and endplate fracture on CT were identified as independent factors associated with IVP.

Factors Associated with Topical Medication Instillation Failure in Glaucoma: VRAMS-QPiG Study.

INTRODUCTION: To report eyedrop instillation techniques and factors associated with instillation failure among glaucoma subjects in the Video-Recorded Assessment of Medication Skill and Questionnaire-based evaluation of Perception in Glaucoma Study. METHODS: In this cross-sectional observational study, subjects were 60 patients with glaucoma (mean ± standard deviation age, 68.4 ± 11.3 years; 30 men) who required ocular hypotensive medication(s). Subjects completed ophthalmologic examinations and the Mini-Cog cognitive function test; their typical eyedrop instillation technique was video-recorded. Subjects rated their technique as successes/failures by questionnaire and two examiners rated the successes/failures based on video assessment. Discrepancy between self-reported and video-assessed success/failure rates of instillation was the main outcome measures. Multivariate logistic regression identified factors in instillation failure. RESULTS: Of 48/56 (86%) self-reported successes, 27/48 (56%) failed based on video assessment; as a result, 32/56 (57%) were inconsistent between subjective and objective assessments. Overall, 30/56 (54%) failed based on video assessment. In the subject-based data model, older age [odds ratio (OR) 0.93/year, P = 0.025] and lower cognitive function score (OR 2.7/score, P = 0.025) were factors in failed instillations. In the eye-based data model, less myopic objective refractive error (OR 0.77/diopter, P = 0.016) and lower visual field foveal threshold (OR 1.1/decibel, P = 0.041) were factors in failures. CONCLUSION: In addition to older age, decreased cognitive function, hyperopia, and decreased foveal sensitivity are risks for failed eyedrop instillation. Treating physicians can screen patients who require guidance by checking the risk factors of instillation failure rather than by relying on patient reports.

Decompression for lumbar spinal stenosis at the intrathecal catheter insertion site during intrathecal baclofen therapy: a case report.

BACKGROUND: Intrathecal baclofen therapy can substantially improve symptoms in most patients with severe spasticity due to traumatic spinal cord injury, multiple sclerosis, or cerebral paresis. To the best of our knowledge, decompression surgeries at the intrathecal catheter insertion site in patients with a preexisting intrathecal pump for drug delivery have not been reported. CASE PRESENTATION: We report the case of a 61-year-old Japanese man with lumbar spinal stenosis who underwent intrathecal baclofen therapy. We performed decompression for lumbar spinal stenosis at the intrathecal catheter insertion site during intrathecal baclofen therapy. The yellow ligament was removed by partial resection of the lamina under a microscope to avoid damage to the intrathecal catheter. The dura mater was distended. No obvious cerebrospinal fluid leakage was observed. Postoperatively, lumbar spinal stenosis symptoms improved, and spasticity remained well controlled with intrathecal baclofen therapy. CONCLUSIONS: This is the first reported case of lumbar spinal stenosis decompression at an intrathecal catheter insertion site during intrathecal baclofen therapy. Preoperative preparation is necessary, as the intrathecal catheter may be replaced during surgery. We performed surgery without removing or replacing the intrathecal catheter, taking care not to damage the spinal cord by migrating the intrathecal catheter.

Efficacy of lutein supplements on macular pigment optical density in highly myopic individuals: A randomized controlled trial.

INTRODUCTION: Lutein supplementation is beneficial in preventing maculae from developing serious ocular diseases. This study aimed to evaluate the efficacy and safety of lutein administration in patients with high myopia (HM). METHODS: In a single-center randomized double-blinded placebo-controlled trial conducted over 24 months, 22 eyes were enrolled in lutein and control groups. Among them, 15 eyes in the lutein group and 13 eyes in the control group completed the study. All patients with HM (axial length > 26.00) were administered lutein (20 mg) or placebo once daily for 6 months. The macular pigment optical density (MPOD), rate of change in MPOD, visual acuity, contrast sensitivity, and electroretinogram after administration were examined at baseline, 3 months, and 6 months. RESULTS: The baseline MPOD in the control and lutein groups was 0.71 ± 0.21 and 0.70 ± 0.22, respectively. The MPOD in the control and lutein groups at 3 months was 0.70 ± 0.21 and 0.70 ± 0.25, respectively, and at 6 months was 0.66 ± 0.20 and 0.72 ± 0.27, respectively, which was not significantly different from those at baseline or between the groups. The MPOD significantly increased from baseline in the lutein group with less than 28.25 mm of axial length at 6 months (from 0.71 ± 0.20 to 0.78 ± 0.22, P = .02, t test). visual acuity, contrast sensitivity, and electroretinogram values were similar between the groups. CONCLUSION: Lutein supplementation showed significant benefits in MPOD augmentation in patients with HM.

Bilateral simultaneous asymmetric hip fracture without major trauma in an elderly patient: a case report.

BACKGROUND: Simultaneous bilateral hip fractures without major trauma in the elderly are rare and usually symmetrical. To the best of our knowledge, only two cases of bilateral simultaneous asymmetric hip fracture in the elderly without major trauma have been reported. CASE PRESENTATION: We present the case of a 90-year-old Japanese man with simultaneous bilateral asymmetric hip fractures with trochanteric fracture on the right side and greater trochanteric fracture on the left side. He complained of dyspnea at midnight and was referred to our emergency department. He was admitted to the internal medicine department for bacterial pneumonia treatment. On the 8th day of hospitalization, he was referred to our orthopedic surgery department for hip pain and was found to have fractures of both hips. Computed tomography findings showed that the left femoral neck fracture was an old fracture, while the left greater trochanteric fracture and the right trochanteric fracture were fresh fractures. He was surgically treated through open reduction and internal fixation with an intramedullary nail on the right and hemiarthroplasty on the left in supine position, performed during the same surgical sessions on the 12th day of hospitalization. CONCLUSIONS: We report a new form of simultaneous bilateral asymmetric hip fracture in the elderly. The fracture types of the case were femoral trochanteric fracture and greater trochanteric fracture of the femur, which were different from the fracture types in the previously reported two cases. Clinicians should be aware of the possibility of simultaneous bilateral hip fractures, especially in the elderly.

Intrathecal baclofen therapy for severe spasticity in an adult with tethered cord syndrome: a case report.

BACKGROUND: Patients with tethered cord syndrome often suffer severe spasticity. To the best of our knowledge, intrathecal baclofen (ITB) therapy in a patient with tethered cord syndrome has not been reported previously. We describe a case in which ITB therapy was useful for treating severe spasticity in an adult with tethered cord syndrome. CASE PRESENTATION: We present the case of a 50-year-old Japanese woman with tethered cord syndrome and related conditions suffering from severe spasticity and pain in the lower limbs. She was born with a lumbosacral myelomeningocele, which was closed in the neonatal period. For 4-5 years before this presentation, spasticity in the lower limbs had been exacerbated without any obvious cause. She received rehabilitation and pharmacotherapy from a local doctor, but symptoms were unimproved, and her previous doctor referred her to this department. A test with 50 µg of intrathecally delivered baclofen showed total relief of spasticity and pain, so a pump was implanted for continuous baclofen delivery. During 24 months of follow-up, spasticity has remained under excellent control with baclofen at 38.5-41.0 µg/day. CONCLUSIONS: ITB therapy proved extremely effective in this adult with severe spasticity from tethered code syndrome.

Effects of French maritime pine bark/bilberry fruit extracts on intraocular pressure for primary open-angle glaucoma.

We tested oral French maritime pine bark (40 mg)/bilberry fruit extract (90 mg) supplements for intraocular pressure-lowering effects in Japanese subjects with primary open-angle glaucoma. Eighteen subjects (29 eyes) were recruited with intraocular pressure of ≥15 mmHg who used one to three bottles of antiglaucoma medications. After a 2-week observation (period 1), subjects ingested a tablet/day of Sante® Glagenox for 4 weeks (period 2). The mean intraocular pressure (17.2 ± 2.3 mmHg) decreased significantly to 15.7 ± 1.9 mmHg (8.7% reduction) at week 4 (p = 0.0046). The mean morning intraocular pressure (14.1 ± 3.1 mmHg) self-measured using the iCare HOME tonometer during period 1 decreased significantly to 13.3 ± 2.9 mmHg (5.7% reduction) during period 2 (p = 0.0291). Blood redox parameters, diacron reactive oxygen metabolites, biologic antioxidant potential, and sulfhydryl tests were unchanged after 4-week supplementation. Intra-subject comparisons, compared to period 1, showed pooled, self-measured, period-2 intraocular pressures was significantly lower in nine subjects (50%), unchanged in six subjects (33%), and elevated in three subjects (17%), suggesting some non-responders. Four-week supplementation with French maritime pine bark/bilberry fruit extracts can further reduce intraocular pressure even in Japanese patients with controlled primary open-angle glaucoma. Further study should confirm the intraocular pressure-lowering effects and mechanisms of this supplement in glaucoma management. The study was registered in UMIN (ID: UMIN000033200).

Patient Satisfaction with Implant Removal after Stabilization Using Percutaneous Pedicle Screws for Traumatic Thoracolumbar Fracture.

CONTEXT: There are no reports of patient satisfaction with implant removal after stabilization using percutaneous pedicle screws (PPS) for traumatic thoracolumbar fracture (TTF). AIMS: The aim of this study was to investigate patient satisfaction with implant removal after stabilization using PPS for TTF. SETTINGS AND DESIGN: A retrospective study. SUBJECTS AND METHODS: The present study included data from 24 patients who underwent posterior stabilization using PPS for single-level TTF following implant removal. The degree of patient satisfaction was evaluated using a questionnaire. We investigated residuary back pain, using the numerical rating scale (NRS) and Oswestry disability index (ODI), and types of occupation. Patients were divided into groups of those with residuary back pain (Group P) and those without (Group N). We evaluated local kyphosis and disc degeneration after implant removal. We investigated whether residuary back pain or types of occupation affect patient satisfaction. STATISTICAL ANALYSIS USED: All statistical analyses were conducted using IBM SPSS statistics. RESULTS: Patients were "extremely satisfied" in 13 cases (54%), "moderately satisfied" in eight cases (33%), and "neither" in three cases (13%). No patients answered "moderately dissatisfied" or "extremely dissatisfied." The mean scores on the NRS and ODI in Group P were 1.8 ± 0.9 and 13.2 ± 9.3, respectively. Patient satisfaction, disc degeneration, and local kyphosis were not significantly different between Group P and Group N. Patient satisfaction was not significantly different between the hard and light workgroups. CONCLUSIONS: Patient satisfaction with implant removal was high regardless of whether persistent back pain existed and did not depend on the type of occupation.

Thoracic extradural malignant melanoma with unknown primary.

Primary extradural spinal melanoma is a very rare lesion. Here, we report a thoracic extradural malignant melanoma in a 77-year-old male. MRI showed a dorsal spinal extradural tumour at the T6-T8 level. The tumour showed hyperintensity on T1W imaging and mixed hypointensity and hyperintensity on T2W imaging. Gadolinium-enhanced MRI showed high enhancement on the lesion. Information on imaging findings for extradural spinal melanoma appears very limited. We discuss the MRI findings from this case, which can be considered typical of extradural spinal melanoma and review the literature.

Cost-effectiveness and budget impact analysis of a patient visit support system for blindness reduction in Japanese patients with glaucoma.

AIM: To evaluate the cost-effectiveness (CE) and budget impact (BI) of introducing a patient visit support system (ACT Pack) along with standard of care (SoC), in glaucoma treatment in Japan. METHODS: A Markov model was designed to estimate the CE and BI of introducing the support system from Japanese payer and governmental perspective, respectively. Inputted data for CE and BI analysis were referred from published literature and based on medical specialists' inputs. Base case scenario for CE considered the support system cost of 30,000 yen per patient per year and a time horizon of 45 years. BI analysis compared the financial impact due to introduction of support system with SoC compared to SoC alone scenario on Japanese healthcare system with a time horizon of 20 years. RESULTS: The base case of CE analysis showed the incremental cost per quality-adjusted life years (QALYs) gained with the support system was 3,241,729 yen/QALY (29,470 USD/QALY). The sensitivity analysis showed that the probability of this support system being cost-effective at a threshold of 5 million yen/QALY (45,455 USD/QALY) was 53.26%. Blindness reduction after introduction of this support system was 8.68%. The BI analysis showed that the introduction of support system will lead to a cumulative cost savings of 1,132 billion yen (10 billion US dollars) for Japanese healthcare system over 20 years of time horizon. LIMITATION: Due to paucity of similar comparative studies, some assumptions were made based on medical specialists' inputs. Death status was not considered in the analysis. CONCLUSION: Introduction of this support system with SoC is cost-effective and will lead to blindness reduction in Japanese patients with glaucoma. Over a 20 year period, it will lead to an overall cost savings of 1,132 billion yen (10 billion US dollars) for the Japanese healthcare system.

Aspergillus terreus spondylodiscitis following an abdominal stab wound: a case report.

BACKGROUND: Aspergillus terreus, a saprophytic fungus, is recognized as an emerging pathogen in various infections in humans. However, bone and joint involvement is uncommon. To the best of our knowledge, only seven cases of spondylodiscitis caused by Aspergillus terreus have been reported previously in humans. We report a case of a patient with Aspergillus terreus spondylodiscitis following an abdominal stab wound. CASE PRESENTATION: A 74-year-old Japanese man with no particular medical history fell from a ladder and sustained a left abdominal stab wound from an L-shaped metal peg. Computed tomography showed the trace of the L-shaped metal peg from the left abdomen to the left rib and left kidney. The scan also showed an anterolateral bone avulsion of the left side of the T12 vertebral body, as well as fractures of the L1 left transverse process and the left 10th-12th ribs. He was hospitalized and treated with conservative therapy for 6 weeks. He was readmitted to the hospital with complaints of sudden back pain, numbness of both legs, and inability to walk 13 weeks after the fall. Magnetic resonance imaging findings were typical of spondylodiscitis. Gadolinium-enhanced T1-weighted magnetic resonance imaging indicated increased signal intensity at T11-T12 vertebral bodies and severe cord compression and epidural abscess at T11-T12 associated with infiltration of soft paravertebral tissues. On the seventh day after admission, he underwent partial laminectomy at T11 and posterior fusion at T9 to L2. The result of his blood culture was negative, but Aspergillus terreus was isolated from the material of T11-T12 intervertebral disc and vertebral bodies. His Aspergillus antigen was positive in a blood examination. Histological examination showed chronic suppurative osteomyelitis. On the 35th day after admission, he underwent anterior fusion at T11 and T12 with a rib bone graft. For 5 months, voriconazole was administered, and he wore a rigid corset. Posterior partial laminectomy at T11 and anterior fusion at T11 and T12 resulted in a good clinical course. The patient's neurological dysfunction was completely recovered, and his back pain disappeared. Two years after the operation, computed tomography was performed and showed bone fusion at T11 and T12. Magnetic resonance imaging revealed no evidence of increased signal intensity at T11-T12 vertebral bodies and severe cord compression and epidural abscess at T11-T12. CONCLUSIONS: To our knowledge, this is the first report of spondylodiscitis caused by Aspergillus terreus after an abdominal penetrating injury. The histological finding of chronic suppurative osteomyelitis and the radiological findings strongly suggested direct inoculation of Aspergillus terreus.

Ocular hypotensive effects of prostaglandin analogs in Japanese patients with normal-tension glaucoma: a literature review.

PURPOSE: This paper aimed to evaluate the intraocular pressure (IOP)-lowering effects of prostaglandin analogs (PGAs) in Japanese patients with normal-tension glaucoma (NTG) by reviewing the current literature. METHODS: In February 2018, database searches were performed in PubMed, Embase, ProQuest, and the Japanese databases JAPICDOC and JMEDPlus. Studies were sorted into two categories: Category 1 consisted of studies of patients with NTG who reported reduced IOP values and Category 2 consisted of studies of patients with NTG who had IOP values at predosing and a final evaluation point. Search terms included ([unoprostone or latanoprost or travoprost or bimatoprost or tafluprost] and [glaucoma] and [Japan or Japanese]). The weighted ocular hypotensive efficacy was calculated. A scatter plot analysis was performed and a regression equation was calculated for each medication. The fitting of each regression equation was evaluated by the least squares method. RESULTS: Eleven articles were eligible for Category 1 and 25 articles for Category 2. In the rank order of IOP-lowering efficacy of PGAs, bimatoprost was the strongest and latanoprost the weakest. Travoprost and tafluprost had almost the same level of ocular hypotensive effect, and both were stronger than latanoprost. The scatter plot analysis showed that all PGAs reduced IOP by 15%-20%. At higher IOP (17-18 mmHg), the ocular hypotensive effect was almost the same with latanoprost, travoprost, and tafluprost. In contrast, at lower IOP (12-15 mmHg), the IOP reduction with latanoprost was weaker than with travoprost or tafluprost. CONCLUSION: This literature review of the ocular hypotensive effects of PGAs in Japanese patients with NTG highlighted that PGAs had different ocular hypotensive effects. Ophthalmologists should understand the IOP-lowering profiles of various PGAs and apply them to patients with NTG on a case-by-case basis. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000032344.

Recurrent upper lumbar disc herniation treated via the transforaminal approach using microendoscopy-assisted lumbar discectomy: a case report.

BACKGROUND: Although microendoscopy-assisted lumbar discectomy for lateral or extraforaminal lumbar disc herniations via the lateral approach has previously been reported, microendoscopy-assisted lumbar discectomy for central or paramedian disc herniations via the lateral approach has not been reported. We report the first case of recurrent upper lumbar disc herniation (L2-L3) treated with microendoscopy-assisted lumbar discectomy via the transforaminal approach. No microendoscopy-assisted lumbar discectomy for recurrent upper lumbar disc herniation via the transforaminal approach has previously been reported. Percutaneous endoscopic lumbar discectomy via the transforaminal approach is very useful as a minimally invasive surgery for disc herniations. We applied percutaneous endoscopic lumbar discectomy via the transforaminal approach, and invented a new microendoscopy-assisted lumbar discectomy via the transforaminal approach. CASE PRESENTATION: A 79-year-old Japanese man was operatively managed for recurrent L2-L3 herniation. An 18 mm skin incision was made approximately 70 mm from the midline to the lateral side to allow a sufficiently angled trajectory to the extraforaminal space. The transforaminal approach was used. The exiting nerve root was identified along its course inferior to the pedicle. The lateral portion of the pars interarticularis and the facet joint was removed using a high-speed drill under the guidance of an endoscope. The tip of the endoscope was set at the lateral side of the dura mater. The dura mater was retracted medially and gently, and the herniated disc fragments were removed safely. All symptoms were relieved postoperatively. Postoperative magnetic resonance imaging demonstrated disappearance of all herniated disc fragments. A postoperative three-dimensional computed tomographic scan demonstrated the complete preservation of the facet joint. CONCLUSIONS: This is the first report of a case of recurrent upper lumbar disc herniation treated with microendoscopy-assisted lumbar discectomy via the transforaminal approach. This procedure allows for the use of a nerve retractor and other instruments to detach adhesions from the dura mater. This procedure has the advantages of clear visualization of the dura mater, exiting nerve root, and traversing nerve root, and diminished risk of nerve injury, and complete preservation of the articular surface of the facet joint.

Thoracic spondylolisthesis and spinal cord compression in diffuse idiopathic skeletal hyperostosis: a case report.

BACKGROUND: Diffuse idiopathic skeletal hyperostosis has long been regarded as a benign asymptomatic clinical entity with an innocuous clinical course. Neurological complications are rare in diffuse idiopathic skeletal hyperostosis. However, if they do occur, the consequences are often significant enough to warrant major neurosurgical intervention. Neurological complications occur when the pathological process of ossification in diffuse idiopathic skeletal hyperostosis extends to other vertebral ligaments, causing ossification of the posterior longitudinal ligaments and/or ossification of the ligamentum flavum. Thoracic spondylolisthesis with spinal cord compression in diffuse idiopathic skeletal hyperostosis has not previously been reported in the literature. CASE PRESENTATION: A 78-year-old Japanese man presented with a 6-month history of gait disturbance. A magnetic resonance imaging scan of his cervical and thoracic spine revealed anterior spondylolisthesis and severe cord compression at T3 to T4 and T10 to T11, as well as high signal intensity in a T2-weighted image at T10/11. Computed tomography revealed diffuse idiopathic skeletal hyperostosis at T4 to T10. He underwent partial laminectomy of T10 and posterior fusion of T9 to T12. The postoperative magnetic resonance imaging revealed resolution of the spinal cord compression and an improvement in the high signal intensity on the T2-weighted image. CONCLUSIONS: We report the first case of thoracic spondylolisthesis and spinal cord compression in diffuse idiopathic skeletal hyperostosis. Neurosurgical intervention resulted in a significant improvement of our patient's neurological symptoms.

Prospective Observational Post-marketing Study of Tafluprost 0.0015%/Timolol 0.5% Combination Ophthalmic Solution for Glaucoma and Ocular Hypertension: Short-Term Efficacy and Safety.

INTRODUCTION: The intraocular pressure (IOP)-lowering effect and safety of tafluprost 0.0015%/timolol maleate 0.5% combination ophthalmic solution (Taf-TFC) were investigated in a real-world clinical setting. METHODS: A prospective up to 2-year (more than 1 year) observational study has been initiated to collect data on the IOP, conjunctival hyperemia score, corneal staining score, and adverse events suffered by patients with glaucoma or ocular hypertension treated at 3 months, and up to 2 years (more than 1 year) after initiating treatment with Taf-TFC. The 3-month findings are reported here. RESULTS: Among 439 patients enrolled at 100 institutions in Japan, most had normal tension glaucoma (45.3%) or primary open angle glaucoma (36.0%). Adverse drug reaction (ADR) occurred in 5.01%. The important ADRs were conjunctival hyperemia (five patients), blepharitis (four patients), and punctate keratitis (two patients). Serious adverse reactions occurred in two patients (three events). In 410 patients with data both before and after treatment, baseline mean IOP was 17.5 ± 5.0 mmHg, and it was significantly decreased after 1, 2, and 3 months (all P < 0.05, paired-t test). IOP was significantly reduced in patients switched to Taf-TFC from either prostaglandin or ß-blocker monotherapy. IOP also decreased significantly in patients switched from a prostaglandin/timolol fixed combination, but not in patients switched from concomitant use of a prostaglandin analog and a ß-blocker. The use of Taf-TFC did not worsen the adherence in most patients. CONCLUSION: Taf-TFC significantly reduced the IOP in patients with glaucoma or ocular hypertension treated in daily clinical practice with controllable or recoverable ADRs in short period. Taf-TFC was effective regardless of treatment patterns, and particularly, Taf-TFC significantly reduced IOP in cases in which requiring the second line therapy as insufficient of monotherapy. FUNDING: Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Anti-diabetic activity of a leaf extract prepared from Salacia reticulata in mice.

The effects of a water extract prepared from the leaves of Salacia reticulata on the absorption of sugars in normal and type 1 diabetic mice were investigated. The simultaneous oral administration of the extract at a dose of 1.0 mg/mouse with maltose or sucrose inhibited the postprandial elevation of the plasma glucose and insulin levels and intestinal alpha-glucosidase activities in mice. In addition, the supply of a 0.01% solution of the extract as drinking water prevented the elevation of the plasma glucose level and intestinal alpha-glucosidase activities in type 1 diabetic mice. This treatment also prevented the elevation of the plasma, pancreatic, and kidney lipid peroxide levels, lowering of the plasma insulin level, and elevation of the kidney aldose reductase activities in diabetic mice. These results suggest that the water extract of the leaves of S. reticulata could be a beneficial food material for the prevention of diabetes and obesity because of its multiple effects.

Effects of bunazosin hydrochloride on ciliary muscle constriction and matrix metalloproteinase activities.

PURPOSE: To clarify the mechanism by which bunazosin hydrochloride (BZ), a selective alpha1-adrenoceptor antagonist, increases uveoscleral outflow. METHODS: The effects of BZ on matrix metalloproteinase (MMP) activities in cultured monkey ciliary muscle cells, and on phenylephrine hydrochloride-induced constriction in bovine ciliary muscles, were examined. Also, the possible additive ocular hypotensive effects of BZ and latanoprost (LP) were evaluated in ocular normotensive monkeys. RESULTS: Although BZ at 10 to 10 M did not increase MMP-2, -3, and -9 activities in the culture medium of ciliary muscle cells, BZ at 10 to 10 M inhibited phenylephrine hydrochloride-induced constriction in ciliary muscles. The maximal reduction in intraocular pressure of concomitant administration of BZ and LP was greater than that of BZ alone and tended to be greater than that of LP alone. CONCLUSION: These findings, in normotensive monkeys, indicate that the mechanism whereby BZ increases uveoscleral outflow is independent of an effect on MMPs and is partly due to relaxation of the ciliary muscle. This effect is different from that of LP, which might help to explain the finding that topical concomitant administration of BZ and LP increased AUC(0-6h) value (IOP reduction) to 201% and 145% of BZ and LP given alone, respectively.

New ethacrynic acid derivatives as potent cytoskeletal modulators in trabecular meshwork cells.

A series of ethacrynic acid (ECA) derivatives were synthesized and examined for ocular hypotensive activity. Efficacy was evaluated in a cell-shape assay, using human trabecular meshwork cells, and cytotoxicity in a (3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay, using cultured bovine trabecular meshwork cells. Many of the derivatives demonstrated efficacy equal to or greater than that of ECA. SA9000 was selected as the most promising candidate for a novel ocular hypotensive drug with few side effects.

Pharmacological characteristics of AFP-168 (tafluprost), a new prostanoid FP receptor agonist, as an ocular hypotensive drug.

To evaluate the pharmacological characteristics of AFP-168 (tafluprost), a new prostaglandin (PG) F(2alpha) derivative, we examined its receptor-binding affinities, intraocular pressure (IOP)-lowering effect, effects on aqueous humor dynamics, and stimulating effect on melanogenesis. The receptor-binding profile for AFP-172, a carboxylic acid of AFP-168, was determined by measuring muscle contractions in an organ bath, inhibition of platelet aggregation, and competitive binding of a radio-labelled ligand. For the IOP-measurement study, ocular normotensive and laser-induced ocular hypertensive cynomolgus monkeys were used, and IOP was measured using a pneumatonograph. For the studies of aqueous humor dynamics, IOP (Goldmann applanation tonometry), fluorophotometry, two-level constant pressure perfusion, and isotope dilution and accumulation techniques were used in ocular normotensive monkeys. The melanin contents in the medium and in the cell bodies of cultured B16-F0 melanoma cells were measured. The affinity for the FP receptor shown by AFP-172 (Ki : 0.4 nm) was 12 times that of PhXA85 ( Ki : 4.7 nm), a carboxylic acid of latanoprost. A single application of AFP-168 at 0.0025% significantly lowered IOP in both ocular normotensive and hypertensive monkeys (3.1 and 11.8 mmHg, respectively, p < 0.01) and latanoprost at 0.005% significantly lowered IOP (2.1 mmHg, p < 0.01 and 9.5 mmHg, p = 0.059 respectively). Once daily instillation of AFP-168 at 0.001, 0.0025, or 0.005% for 5 days in normotensive monkeys significantly reduced IOP not only for a few hours, but also at the drug-trough time 24hr after application. Latanoprost at 0.005% also reduced IOP, but not at the drug-trough time. AFP-168 decreased IOP mainly by increasing uveoscleral outflow by 65% (p < 0.05) and, as sometimes seen with other prostanoids, also increased total outflow facility (33% increase, p < 0.05). In cultured B16-F0 melanoma cells, AFP-172 (100 microM) did not stimulate melanogenesis, but PhXA85 (100 microM) did. These findings indicate that AFP-168 has a high affinity for the prostanoid FP receptor, has potent IOP-lowering effects in both ocular normotensive and hypertensive monkeys that exceed those of latanoprost, and has less stimulating effect on melanogenesis in melanoma cells.