Hitoshi Yasuda - Academia.edu (original) (raw)
Papers by Hitoshi Yasuda
Diabetic Medicine, 2008
Aims The long‐term efficacy of epalrestat, an aldose reductase inhibitor, in improving subjectiv... more Aims The long‐term efficacy of epalrestat, an aldose reductase inhibitor, in improving subjective symptoms and nerve function was comprehensively assessed to identify patients with diabetic peripheral neuropathy who responded to epalrestat treatment.Methods Stratified analyses were conducted on data from patients in the Aldose Reductase Inhibitor—Diabetes Complications Trial (ADCT). The ADCT included patients with diabetic peripheral neuropathy, median motor nerve conduction velocity ≥ 40 m/s and with glycated haemoglobin (HbA1c) ≤ 9.0%. Longitudinal data on HbA1c and subjective symptoms of the patients for 3 years were analysed (epalrestat n = 231, control subjects n = 273). Stratified analyses based on background variables (glycaemic control, grades of retinopathy or proteinuria) were performed to examine the relationship between subjective symptoms and nerve function. Multiple logistic regression analyses were conducted.Results Stratified subgroup analyses revealed significant...
Internal Medicine, 2000
Objective Evaluation of metabolic states and chronic complications is essential for maintaining a... more Objective Evaluation of metabolic states and chronic complications is essential for maintaining a high quality of care for diabetic patients. Wehave assessed the quality of care in routine outpatient clinics for diabetic subjects in our university hospital, and compared with those in a newly introduced standardized clinic to evaluate the newcare system. Methods The quality of care was assessed by the chart review in 1995, and compared with those from 1996-1997 in the "Diabetes Follow-up Clinic" which is systematically designed for the standardized care. Patients The subjects were recruited among 860 patients who visited the outpatient clinic in July and August of 1995 with a diagnosis of diabetes or glucose intolerance. Six hundred seventy-two patients whose follow-up period had been more than 6 months with clinically diagnosed diabetes wereused for the analysis. Results Laboratory tests such as determination of HbAlc, and serum levels of lipids and creatinine were performed in more than 90%of the patients in the routine outpatient clinics. However, ophthalmology referral, 24-hour urine collection for the determination of creatinine clearance and albumin excretion, and electrocardiograms were not well performed and were incompletely documented (40-60 % of the patients within a previous year and 70-80%in the last 2 years). In the standardized "Diabetes Follow-up Clinic", only four out of 555 diabetic patients failed to collect their 24-hour urine, and all participants had ankle blood pressure measurements,nerve conduction study, and nylon mono filament tests, etc. Furthermore, more than 95 % of the patients had funduscopic examinations by ophthalmologists as well as records of electrocardiogram. Conclusion Introduction of the standardized "Diabetes Follow-up Clinic" may be one of the choices for increasing the quality of outpatient care and for the prevention of chronic diabetic complications.
Diabetes, 1989
The effect of a newly developed oral agent, prostaglandin E 1 (PGE,) analogue TFC 612, on diabeti... more The effect of a newly developed oral agent, prostaglandin E 1 (PGE,) analogue TFC 612, on diabetic neuropathy was studied by giving it for 6 wk to streptozocin-induced diabetic rats that had been diabetic for 3 mo and was compared with the effects of aldose reductase inhibitor ONO 2235. Although both compounds improved decreased motor nerve conduction velocity, the effect of TFC 612 continued during the 6 wk of treatment, whereas that of ONO 2235 became weaker from wk 4. The abnormality in sciatic nerve sorbitol and myo-inositol levels was reversed with ONO 2235, whereas it was unchanged with TFC 612. With the laser Doppler flowmetry technique, a decrease in the sciatic nerve blood flow in diabetic rats was shown to improve with both compounds, but TFC 612 had a greater effect than ONO 2235, and the increased lactate level of the diabetic nerve was corrected with both compounds, suggesting that both may be associated with the amelioration of ischemia in the diabetic endoneurium. Both TFC 612 and ONO 2235 partially but significantly normalized decreased fiber size in diabetic rats. On the other hand, TFC 612 completely normalized the dilated lumen area in diabetic rats, whereas ONO 2235 did not. These results suggest that the PGE, analogue TFC 612 has a significant effect on diabetic neuropathy, possibly via vasotropic action, and may be a potent compound for the treatment of diabetic neuropathy.
American Journal of Physiology-Endocrinology and Metabolism, 2011
Tumor necrosis factor (TNF)-α is a potent proinflammatory cytokine involved in the pathogenesis o... more Tumor necrosis factor (TNF)-α is a potent proinflammatory cytokine involved in the pathogenesis of diabetic neuropathy. We inactivated TNF-α to determine if it is a valid therapeutic target for the treatment of diabetic neuropathy. We effected the inactivation in diabetic neuropathy using two approaches: by genetic inactivation of TNF-α (TNF-α−/− mice) or by neutralization of TNF-α protein using the monoclonal antibody infliximab. We induced diabetes using streptozotocin in wild-type and TNF-α−/− mice. We measured serum TNF-α concentration and the level of TNF-α mRNA in the dorsal root ganglion (DRG) and evaluated nerve function by a combination of motor (MNCV) and sensory (SNCV) nerve conduction velocities and tail flick test, as well as cytological analysis of intraepidermal nerve fiber density (IENFD) and immunostaining of DRG for NF-κB p65 serine-276 phosphorylated and cleaved caspase-3. Compared with nondiabetic mice, TNF-α+/+ diabetic mice displayed significant impairments of ...
Journal of the Peripheral Nervous System, 2000
Diabetes, 2003
Streptozocin (STZ)-induced diabetic rats show hyperalgesia that is partially attributed to altere... more Streptozocin (STZ)-induced diabetic rats show hyperalgesia that is partially attributed to altered protein kinase C (PKC) activity. Both attenuated neuronal nitric oxide synthase (nNOS)-cGMP system and tetrodotoxin-resistant (TTX-R) Na channels in dorsal root ganglion neurons may be involved in diabetic hyperalgesia. We examined whether PKCβ inhibition ameliorates diabetic hyperalgesia and, if so, whether the effect is obtained through action on neurons by testing nociceptive threshold in normal and STZ-induced diabetic rats treated with or without PKCβ-selective inhibitor LY333531 (LY) and by assessing the implication of LY in either nNOS-cGMP system or TTX-R Na channels of isolated dorsal root ganglion neurons. The decreased nociceptive threshold in diabetic rats was improved either after 4 weeks of LY treatment or with a single intradermal injection into the footpads. The treatment of LY for 6 weeks significantly decreased p-PKCβ and ameliorated a decrease in cGMP content in dors...
Kidney International, 2001
the alleles other than A21 was not different among each group. Dinucleotide repeat polymorphism o... more the alleles other than A21 was not different among each group. Dinucleotide repeat polymorphism of matrix metalloprotein-The calculated odds ratio for nephropathy in the noncarrier, ase-9 gene is associated with diabetic nephropathy. heterozygote, or homozygote of A21 allele was 3.38, 1.97, and Background. Although genetic susceptibility has been pro-0.2, respectively. Furthermore, the promoter assay for the posed as an important factor for the development and progres-MMP-9 gene revealed that the A21 allele had a higher promoter sion of diabetic nephropathy, the definitive gene has not been activity compared with other alleles. No significant correlation identified. To identify the genetic marker for diabetic nephropwas observed between serum MMP-9 concentrations and the athy, we examined the association between the (A-C)n dinucle-MMP-9 gene polymorphism. otide repeat polymorphism upstream of the matrix metallopro-Conclusion. These results indicate that the patients with A21 teinase-9 (MMP-9) gene and diabetic nephropathy in a group allele of the MMP-9 gene may be protected from the developof Japanese patients with type 2 diabetes. ment and progression of diabetic nephropathy. Thus, the micro-Methods. Patients were divided into three groups based on satellite polymorphism upstream of the MMP-9 gene could be their urinary albumin excretion rate (AER) and the stage of a useful genetic marker for diabetic nephropathy. diabetic retinopathy as follows: uncomplicated group (U), normal albuminuria (AER Ͻ20 g/min) without proliferative retinopathy and with the duration of diabetes more than 20 years (N ϭ 32); microalbuminuria group (M), 20 Յ AER Ͻ 200 g/ Diabetic nephropathy is one of the most common causes min (N ϭ 155); overt nephropathy group (O), AER Ն 200 g/ of renal death in various countries, including Japan. Poor min (N ϭ 63). The region containing the dinucleotide repeat glycemic control of diabetes has been indicated as the upstream of MMP-9 gene was amplified by polymerase chain reaction (PCR). The amplified products were analyzed with 7% Key words: type 2 diabetes, genetic marker, A21 allele, progressive renal disease, Japanese type 2 diabetes, microsatellite polymorphism. the overaccumulation of extracellular matrix (ECM) proteins, such as type IV collagen, in the glomerular mesan
The FASEB Journal, 2000
Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes ca... more Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes causes vascular complications. We have recently shown that a PKC  inhibitor ameliorates not only early diabetes-induced glomerular dysfunction such as glomerular hyperfiltration and albuminuria, but also overexpression of glomerular mRNA for transforming growth factor 1 (TGF-1) and extracellular matrix (ECM) proteins in streptozotocin-induced diabetic rats, a model for type 1 diabetes. In this study, we examined the long-term effects of a PKC  inhibitor on glomerular histology as well as on biochemical and functional abnormalities in glomeruli of db/db mice, a model for type 2 diabetes. Administration of a PKC  inhibitor reduced urinary albumin excretion rates and inhibited glomerular PKC activation in diabetic db/db mice. Administration of a PKC  inhibitor also prevented the mesangial expansion observed in diabetic db/db mice, possibly through attenuation of glomerular expression of TGF- and ECM proteins such as fibronectin and type IV collagen. These findings provide the first in vivo evidence that the long-term inhibition of PKC activation in the renal glomeruli can ameliorate glomerular pathologies in diabetic state, and thus suggest that a PKC  inhibitor might be an useful therapeutic strategy for the treatment of diabetic nephropathy.
Journal of the Peripheral Nervous System, 2000
Proceedings of the …, 1985
The number of capillaries per mm2, minimum intercapillary distance, number of endothelial nuclei ... more The number of capillaries per mm2, minimum intercapillary distance, number of endothelial nuclei per capillary section, and percentage of capillaries closed were evaluated in transverse sections of fascicles of 45 control and 36 diabetic sural nerves. All controls and patients were prospectively studied to ascertain their diabetic and neuropathic status. An index of pathology was introduced and it was found to provide a sensitive and reliable measurement of the presence and severity of neuropathy. The number of capillaries and minimum intercapillary distance of diabetic nerves were not significantly different from those of controls (P > 0.05). Diabetic nerves exhibited a small but statistically significant increase in the number of endothelial nuclei per capillary that was positively correlated with the severity of neuropathy. The most striking abnormality was the statistically significant increase in the percentage of capillaries closed in patients with neuropathy as compared to those without neuropathy and controls. Among diabetics, this percentage increased with the severity of neuropathy (P = 0.008). The two capillary abnormalities that have been demonstrated may play a role in the development of diabetic polyneuropathy.
Neuroreport, 2006
Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for NeuroReport. Ente... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for NeuroReport. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining ...
Clinical …, 2007
A 73-year-old woman was admitted to our hospital because of persistent high fever and cough, gene... more A 73-year-old woman was admitted to our hospital because of persistent high fever and cough, generalized myalgia, and renal dysfunction. Laboratory examination revealed severe inflammatory signs, pulmonary fibrosis, progression of renal impairment with active nephritic urinary sediments, and a high titer of myeloperoxidase-antineutrophil cytoplasmic antibody, indicating that she might have microscopic polyangiitis with interstitial pneumonia and rapidly progressive glomerulonephritis. Her renal biopsy, however, showed tubulointerstitial changes with mild glomerular abnormalities, and renal angiography revealed that she had vascular lesions of medium-sized arteries, which were compatible with classical polyarteritis nodosa. Tissue biopsy of the clinically affected organ should be considered in anyone suspected to have vasculitis.
Journal of Neurology, Neurosurgery & Psychiatry, 2004
Background: Normal pressure hydrocephalus (NPH) is considered to be a treatable form of dementia,... more Background: Normal pressure hydrocephalus (NPH) is considered to be a treatable form of dementia, because cerebrospinal fluid (CSF) shunting can lessen symptoms. However, neuroimaging has failed to predict when shunting will be effective. Objective: To investigate whether 1 H (proton) magnetic resonance (MR) spectroscopy could predict functional outcome in patients after shunting. Methods: Neurological state including Hasegawa's dementia scale, gait, continence, and the modified Rankin scale were evaluated in 21 patients with secondary NPH who underwent ventriculo-peritoneal shunting. Outcomes were measured postoperatively at one and 12 months and were classified as excellent, fair, or poor. MR spectra were obtained from left hemispheric white matter. Results: Significant preoperative differences in N-acetyl aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) were noted between patients with excellent and poor outcome at one month (p = 0.0014 and 0.0036, respectively). Multiple regression analysis linked higher preoperative NAA/Cr ratio, gait score, and modified Rankin scale to better one month outcome. Predictive value, sensitivity, and specificity for excellent outcome following shunting were 95.2%, 100%, and 87.5%. Multiple regression analysis indicated that NAA/Cho had the best predictive value for one year outcome (p = 0.0032); predictive value, sensitivity, and specificity were 89.5%, 90.0%, and 88.9%. Conclusions: MR spectroscopy predicted long term post-shunting outcomes in patients with secondary NPH, and it would be a useful assessment tool before lumbar drainage.
The FASEB Journal, 2000
Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes ca... more Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes causes vascular complications. We have recently shown that a PKC ß inhibitor ameliorates not only early diabetes-induced glomerular dysfunction such as glomerular hyperfiltration ...
Diabetic Medicine, 2008
Aims The long‐term efficacy of epalrestat, an aldose reductase inhibitor, in improving subjectiv... more Aims The long‐term efficacy of epalrestat, an aldose reductase inhibitor, in improving subjective symptoms and nerve function was comprehensively assessed to identify patients with diabetic peripheral neuropathy who responded to epalrestat treatment.Methods Stratified analyses were conducted on data from patients in the Aldose Reductase Inhibitor—Diabetes Complications Trial (ADCT). The ADCT included patients with diabetic peripheral neuropathy, median motor nerve conduction velocity ≥ 40 m/s and with glycated haemoglobin (HbA1c) ≤ 9.0%. Longitudinal data on HbA1c and subjective symptoms of the patients for 3 years were analysed (epalrestat n = 231, control subjects n = 273). Stratified analyses based on background variables (glycaemic control, grades of retinopathy or proteinuria) were performed to examine the relationship between subjective symptoms and nerve function. Multiple logistic regression analyses were conducted.Results Stratified subgroup analyses revealed significant...
Internal Medicine, 2000
Objective Evaluation of metabolic states and chronic complications is essential for maintaining a... more Objective Evaluation of metabolic states and chronic complications is essential for maintaining a high quality of care for diabetic patients. Wehave assessed the quality of care in routine outpatient clinics for diabetic subjects in our university hospital, and compared with those in a newly introduced standardized clinic to evaluate the newcare system. Methods The quality of care was assessed by the chart review in 1995, and compared with those from 1996-1997 in the "Diabetes Follow-up Clinic" which is systematically designed for the standardized care. Patients The subjects were recruited among 860 patients who visited the outpatient clinic in July and August of 1995 with a diagnosis of diabetes or glucose intolerance. Six hundred seventy-two patients whose follow-up period had been more than 6 months with clinically diagnosed diabetes wereused for the analysis. Results Laboratory tests such as determination of HbAlc, and serum levels of lipids and creatinine were performed in more than 90%of the patients in the routine outpatient clinics. However, ophthalmology referral, 24-hour urine collection for the determination of creatinine clearance and albumin excretion, and electrocardiograms were not well performed and were incompletely documented (40-60 % of the patients within a previous year and 70-80%in the last 2 years). In the standardized "Diabetes Follow-up Clinic", only four out of 555 diabetic patients failed to collect their 24-hour urine, and all participants had ankle blood pressure measurements,nerve conduction study, and nylon mono filament tests, etc. Furthermore, more than 95 % of the patients had funduscopic examinations by ophthalmologists as well as records of electrocardiogram. Conclusion Introduction of the standardized "Diabetes Follow-up Clinic" may be one of the choices for increasing the quality of outpatient care and for the prevention of chronic diabetic complications.
Diabetes, 1989
The effect of a newly developed oral agent, prostaglandin E 1 (PGE,) analogue TFC 612, on diabeti... more The effect of a newly developed oral agent, prostaglandin E 1 (PGE,) analogue TFC 612, on diabetic neuropathy was studied by giving it for 6 wk to streptozocin-induced diabetic rats that had been diabetic for 3 mo and was compared with the effects of aldose reductase inhibitor ONO 2235. Although both compounds improved decreased motor nerve conduction velocity, the effect of TFC 612 continued during the 6 wk of treatment, whereas that of ONO 2235 became weaker from wk 4. The abnormality in sciatic nerve sorbitol and myo-inositol levels was reversed with ONO 2235, whereas it was unchanged with TFC 612. With the laser Doppler flowmetry technique, a decrease in the sciatic nerve blood flow in diabetic rats was shown to improve with both compounds, but TFC 612 had a greater effect than ONO 2235, and the increased lactate level of the diabetic nerve was corrected with both compounds, suggesting that both may be associated with the amelioration of ischemia in the diabetic endoneurium. Both TFC 612 and ONO 2235 partially but significantly normalized decreased fiber size in diabetic rats. On the other hand, TFC 612 completely normalized the dilated lumen area in diabetic rats, whereas ONO 2235 did not. These results suggest that the PGE, analogue TFC 612 has a significant effect on diabetic neuropathy, possibly via vasotropic action, and may be a potent compound for the treatment of diabetic neuropathy.
American Journal of Physiology-Endocrinology and Metabolism, 2011
Tumor necrosis factor (TNF)-α is a potent proinflammatory cytokine involved in the pathogenesis o... more Tumor necrosis factor (TNF)-α is a potent proinflammatory cytokine involved in the pathogenesis of diabetic neuropathy. We inactivated TNF-α to determine if it is a valid therapeutic target for the treatment of diabetic neuropathy. We effected the inactivation in diabetic neuropathy using two approaches: by genetic inactivation of TNF-α (TNF-α−/− mice) or by neutralization of TNF-α protein using the monoclonal antibody infliximab. We induced diabetes using streptozotocin in wild-type and TNF-α−/− mice. We measured serum TNF-α concentration and the level of TNF-α mRNA in the dorsal root ganglion (DRG) and evaluated nerve function by a combination of motor (MNCV) and sensory (SNCV) nerve conduction velocities and tail flick test, as well as cytological analysis of intraepidermal nerve fiber density (IENFD) and immunostaining of DRG for NF-κB p65 serine-276 phosphorylated and cleaved caspase-3. Compared with nondiabetic mice, TNF-α+/+ diabetic mice displayed significant impairments of ...
Journal of the Peripheral Nervous System, 2000
Diabetes, 2003
Streptozocin (STZ)-induced diabetic rats show hyperalgesia that is partially attributed to altere... more Streptozocin (STZ)-induced diabetic rats show hyperalgesia that is partially attributed to altered protein kinase C (PKC) activity. Both attenuated neuronal nitric oxide synthase (nNOS)-cGMP system and tetrodotoxin-resistant (TTX-R) Na channels in dorsal root ganglion neurons may be involved in diabetic hyperalgesia. We examined whether PKCβ inhibition ameliorates diabetic hyperalgesia and, if so, whether the effect is obtained through action on neurons by testing nociceptive threshold in normal and STZ-induced diabetic rats treated with or without PKCβ-selective inhibitor LY333531 (LY) and by assessing the implication of LY in either nNOS-cGMP system or TTX-R Na channels of isolated dorsal root ganglion neurons. The decreased nociceptive threshold in diabetic rats was improved either after 4 weeks of LY treatment or with a single intradermal injection into the footpads. The treatment of LY for 6 weeks significantly decreased p-PKCβ and ameliorated a decrease in cGMP content in dors...
Kidney International, 2001
the alleles other than A21 was not different among each group. Dinucleotide repeat polymorphism o... more the alleles other than A21 was not different among each group. Dinucleotide repeat polymorphism of matrix metalloprotein-The calculated odds ratio for nephropathy in the noncarrier, ase-9 gene is associated with diabetic nephropathy. heterozygote, or homozygote of A21 allele was 3.38, 1.97, and Background. Although genetic susceptibility has been pro-0.2, respectively. Furthermore, the promoter assay for the posed as an important factor for the development and progres-MMP-9 gene revealed that the A21 allele had a higher promoter sion of diabetic nephropathy, the definitive gene has not been activity compared with other alleles. No significant correlation identified. To identify the genetic marker for diabetic nephropwas observed between serum MMP-9 concentrations and the athy, we examined the association between the (A-C)n dinucle-MMP-9 gene polymorphism. otide repeat polymorphism upstream of the matrix metallopro-Conclusion. These results indicate that the patients with A21 teinase-9 (MMP-9) gene and diabetic nephropathy in a group allele of the MMP-9 gene may be protected from the developof Japanese patients with type 2 diabetes. ment and progression of diabetic nephropathy. Thus, the micro-Methods. Patients were divided into three groups based on satellite polymorphism upstream of the MMP-9 gene could be their urinary albumin excretion rate (AER) and the stage of a useful genetic marker for diabetic nephropathy. diabetic retinopathy as follows: uncomplicated group (U), normal albuminuria (AER Ͻ20 g/min) without proliferative retinopathy and with the duration of diabetes more than 20 years (N ϭ 32); microalbuminuria group (M), 20 Յ AER Ͻ 200 g/ Diabetic nephropathy is one of the most common causes min (N ϭ 155); overt nephropathy group (O), AER Ն 200 g/ of renal death in various countries, including Japan. Poor min (N ϭ 63). The region containing the dinucleotide repeat glycemic control of diabetes has been indicated as the upstream of MMP-9 gene was amplified by polymerase chain reaction (PCR). The amplified products were analyzed with 7% Key words: type 2 diabetes, genetic marker, A21 allele, progressive renal disease, Japanese type 2 diabetes, microsatellite polymorphism. the overaccumulation of extracellular matrix (ECM) proteins, such as type IV collagen, in the glomerular mesan
The FASEB Journal, 2000
Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes ca... more Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes causes vascular complications. We have recently shown that a PKC  inhibitor ameliorates not only early diabetes-induced glomerular dysfunction such as glomerular hyperfiltration and albuminuria, but also overexpression of glomerular mRNA for transforming growth factor 1 (TGF-1) and extracellular matrix (ECM) proteins in streptozotocin-induced diabetic rats, a model for type 1 diabetes. In this study, we examined the long-term effects of a PKC  inhibitor on glomerular histology as well as on biochemical and functional abnormalities in glomeruli of db/db mice, a model for type 2 diabetes. Administration of a PKC  inhibitor reduced urinary albumin excretion rates and inhibited glomerular PKC activation in diabetic db/db mice. Administration of a PKC  inhibitor also prevented the mesangial expansion observed in diabetic db/db mice, possibly through attenuation of glomerular expression of TGF- and ECM proteins such as fibronectin and type IV collagen. These findings provide the first in vivo evidence that the long-term inhibition of PKC activation in the renal glomeruli can ameliorate glomerular pathologies in diabetic state, and thus suggest that a PKC  inhibitor might be an useful therapeutic strategy for the treatment of diabetic nephropathy.
Journal of the Peripheral Nervous System, 2000
Proceedings of the …, 1985
The number of capillaries per mm2, minimum intercapillary distance, number of endothelial nuclei ... more The number of capillaries per mm2, minimum intercapillary distance, number of endothelial nuclei per capillary section, and percentage of capillaries closed were evaluated in transverse sections of fascicles of 45 control and 36 diabetic sural nerves. All controls and patients were prospectively studied to ascertain their diabetic and neuropathic status. An index of pathology was introduced and it was found to provide a sensitive and reliable measurement of the presence and severity of neuropathy. The number of capillaries and minimum intercapillary distance of diabetic nerves were not significantly different from those of controls (P > 0.05). Diabetic nerves exhibited a small but statistically significant increase in the number of endothelial nuclei per capillary that was positively correlated with the severity of neuropathy. The most striking abnormality was the statistically significant increase in the percentage of capillaries closed in patients with neuropathy as compared to those without neuropathy and controls. Among diabetics, this percentage increased with the severity of neuropathy (P = 0.008). The two capillary abnormalities that have been demonstrated may play a role in the development of diabetic polyneuropathy.
Neuroreport, 2006
Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for NeuroReport. Ente... more Close Window. Close Window. Thank you for choosing to subscribe to the eTOC for NeuroReport. Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining ...
Clinical …, 2007
A 73-year-old woman was admitted to our hospital because of persistent high fever and cough, gene... more A 73-year-old woman was admitted to our hospital because of persistent high fever and cough, generalized myalgia, and renal dysfunction. Laboratory examination revealed severe inflammatory signs, pulmonary fibrosis, progression of renal impairment with active nephritic urinary sediments, and a high titer of myeloperoxidase-antineutrophil cytoplasmic antibody, indicating that she might have microscopic polyangiitis with interstitial pneumonia and rapidly progressive glomerulonephritis. Her renal biopsy, however, showed tubulointerstitial changes with mild glomerular abnormalities, and renal angiography revealed that she had vascular lesions of medium-sized arteries, which were compatible with classical polyarteritis nodosa. Tissue biopsy of the clinically affected organ should be considered in anyone suspected to have vasculitis.
Journal of Neurology, Neurosurgery & Psychiatry, 2004
Background: Normal pressure hydrocephalus (NPH) is considered to be a treatable form of dementia,... more Background: Normal pressure hydrocephalus (NPH) is considered to be a treatable form of dementia, because cerebrospinal fluid (CSF) shunting can lessen symptoms. However, neuroimaging has failed to predict when shunting will be effective. Objective: To investigate whether 1 H (proton) magnetic resonance (MR) spectroscopy could predict functional outcome in patients after shunting. Methods: Neurological state including Hasegawa's dementia scale, gait, continence, and the modified Rankin scale were evaluated in 21 patients with secondary NPH who underwent ventriculo-peritoneal shunting. Outcomes were measured postoperatively at one and 12 months and were classified as excellent, fair, or poor. MR spectra were obtained from left hemispheric white matter. Results: Significant preoperative differences in N-acetyl aspartate (NAA)/creatine (Cr) and NAA/choline (Cho) were noted between patients with excellent and poor outcome at one month (p = 0.0014 and 0.0036, respectively). Multiple regression analysis linked higher preoperative NAA/Cr ratio, gait score, and modified Rankin scale to better one month outcome. Predictive value, sensitivity, and specificity for excellent outcome following shunting were 95.2%, 100%, and 87.5%. Multiple regression analysis indicated that NAA/Cho had the best predictive value for one year outcome (p = 0.0032); predictive value, sensitivity, and specificity were 89.5%, 90.0%, and 88.9%. Conclusions: MR spectroscopy predicted long term post-shunting outcomes in patients with secondary NPH, and it would be a useful assessment tool before lumbar drainage.
The FASEB Journal, 2000
Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes ca... more Activation of protein kinase C (PKC) is implicated as an important mechanism by which diabetes causes vascular complications. We have recently shown that a PKC ß inhibitor ameliorates not only early diabetes-induced glomerular dysfunction such as glomerular hyperfiltration ...