Prognostic Significance of Asymptomatic Cerebral Infarction in Patients After Cardiac Catheterization.

Recent studies have showed that asymptomatic cerebral infarction (ACI) developed in a reasonable number of patients after cardiac catheterization. However, no study has investigated the long-term prognostic impact of ACI after cardiac catheterization. We investigated whether ACI after cardiac catheterization affects long-term mortality and subsequent cardiovascular events.We retrospectively enrolled patients who underwent cardiac catheterization before cardiac surgery and cerebral diffusion-weighted magnetic resonance imaging (DWI). The incidence and clinical features of ACI were investigated. The long-term prognosis, including all-cause mortality and subsequent major cardiovascular events (MACE; all-cause mortality, stroke, acute myocardial infarction, fatal arrhythmia, and hospitalized heart failure), was also assessed.A total of 203 patients were enrolled. Of these, 10.3% had ACI diagnosed by DWI. There were no differences in baseline characteristics between patients with and without ACI, except more frequent history of symptomatic stroke in patients with ACI. In the Kaplan-Meier analysis during a median follow-up of 1009 days, the patients with ACI showed worse mortality and a slightly higher occurrence of MACE compared with those without ACI (P = 0.01 and P = 0.08, respectively). In addition, ACI was a prognostic marker independent of age, surgery type, and history of stroke.ACI after cardiac catheterization frequently developed and was also associated with long-term prognosis. It may be an independent prognostic marker in high-risk patients who underwent subsequent cardiac surgery.

Plaque characteristics and prognosis in patients with peripheral arterial disease by angioscopic analysis.

BACKGROUND: The plaques with higher grade of yellow color by angioscopy are reported to be associated with vulnerability leading to adverse outcomes in coronary artery diseases. However, no studies have been performed for peripheral artery disease (PAD). We aimed to evaluate the relationship of angioscopic findings of peripheral arteries with the long-term prognosis. METHODS: Angioscopy of iliac or femoropopliteal artery was performed before endovascular therapy in patients with PAD. The local plaque color and presence of thrombus were evaluated. Multivariable Cox regression models were used to estimate hazard ratio (HR) for all-cause mortality or major adverse cardiovascular event (MACE) related to the plaque colors as well as presence of thrombus. RESULTS: Among 67 patients, 49.3% had intensive yellow plaques (group H) and the rest had light yellow to yellow ones (group L). Thrombus was detected in 74.6% of the patients and the presence was not different between the two groups. In Kaplan-Meier analysis during a median follow-up of 976 days and 757 days, group H showed increased mortality and MACE compared with group L (p <0.01 for both). Multivariable analysis demonstrated that the intensive yellow color of plaque was independently associated with mortality and MACE [HR: 11.48, 95% confidence interval (CI): 2.19-211.1 and HR: 3.81, 95% CI: 1.36-13.48, respectively] after adjusting for the presence of thrombus. CONCLUSIONS: The yellow color intensity in local plaques by angioscopy may be a novel predictor of long-term prognosis in patients with PAD, regardless of the presence of thrombus.

Impact of pericardial fluid glucose level and computed tomography attenuation values on diagnosis of malignancy-related pericardial effusion.

BACKGROUND: We evaluated malignancy according to the characteristics of pericardial fluid in symptomatic Japanese patients undergoing pericardiocentesis and computed tomography (CT). METHODS: This was a retrospective, single-center, observational study of 125 symptomatic patients undergoing pericardiocentesis. The patients were classified into two groups: a malignancy group and a non-malignancy group, according to the primary disease and cytology of the pericardial effusion (PE). We compared the pericardial fluid sample and CT measurements between both groups. RESULTS: All patients were diagnosed as having exudative PE by Light's criteria. PE with malignant cells was demonstrated in 76.8% of the malignancy group patients. Pericardial to serum lactate dehydrogenase (LDH) ratio > 0.6, as one of Light's criteria, was associated with malignancy (p = 0.017). Lower serum brain natriuretic peptide (BNP) concentration was also associated with malignancy (BNP: 126.9 ± 89.8 pg/ml vs 409.2 ± 97.7 pg/ml, malignancy vs non-malignancy groups, respectively; p = 0.037). A significant difference was observed in pericardial fluid glucose level between the malignancy and non-malignancy groups (pericardial fluid glucose: 78.24 ± 48.29 mg/dl vs 98.41 ± 44.85, respectively; p = 0.048). Moreover, CT attenuation values (Hounsfield units (HU)) tended to be higher in the malignancy group vs the non-malignancy group (22.7 [interquartile range (IQR), 17.4-26.0] vs 17.4 [IQR, 13.7-26.4], respectively; p = 0.08). The sensitivity and specificity of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 40.9% and 89.6%, respectively, in the malignancy group. The positive- and negative predictive values of pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were 85.7% and 50.0%, respectively, in the malignancy group. Pericardial fluid glucose level ≤ 70 mg/dl and CT attenuation values > 20 HU were cutoff values associated with malignancy (p = 0.012). CONCLUSIONS: Lower pericardial fluid glucose level with higher CT attenuation values may suggest malignancy-related PE.

Impact of Neointimal Condition and Platelet Reactivity on Intrastent Thrombus at Long-Term Follow-up After 2nd- and 3rd-Generation Drug-Eluting Stent Implantation　- Insights From a Coronary Angioscopy and Pharmacodynamic Study.

BACKGROUND: Although the incidence of very late stent failure (VLSF) is reduced with newer generation drug-eluting stent (DES), the mechanism of VLSF has not been fully explored.Methods and Results:This study evaluated both local vascular healing using coronary angioscopy and systemic factors determined by platelet reactivity at long-term follow-up after 2nd- and 3rd-generation DES implantation in patients with acute coronary syndrome. Coronary angioscopy was performed to assess neointimal coverage (NIC), yellow color (YC) grade and presence of thrombus. The obtained findings were compared with 2nd- and 3rd-DES. Platelet aggregation was assessed by light transmittance aggregometry. 100 consecutive patients were prospectively enrolled: 2nd- (n=50) and 3rd-DES (n=50). 3rd-DES patients had significantly higher NIC grade and lower YC grade compared with 2nd-DES. The presence of thrombus was tended to be lower with 3rd-DES than with 2nd-DES (8% vs. 18%, P=0.11). Patients with thrombus had significantly higher maximum platelet aggregation and higher prevalence of high on-treatment platelet reactivity (HPR) than those without thrombus. Multivariable analysis showed stent strut exposure and HPR as independent predictors of thrombus. CONCLUSIONS: Newer generation DES contribute to better vascular healing depending on the degree of neointimal coverage. In addition to local factors at the stented lesion, systemic factors such as degree of platelet reactivity might also contribute to VLSF.

Retrograde-angioscopy guided wiring technique in chronic total occlusion lead to successful revascularization.

Endovascular therapy (EVT) was performed in two cases with chronic total occlusion (CTO) of superficial femoral artery. In these cases, angioscopy was deployed in the backyard of the CTO lesion from popliteal artery retrogradely, then the guidewire was advanced from antegrade. When the wire crossed the distal of the CTO lesion, the wire penetration was clearly visualized by the retrograde-angioscopy. Therefore, wire crossing of CTO into the distal true lumen was certainly confirmed, and EVT was successful. .

Long-term effects of non-retrieved inferior vena cava filters on recurrences of venous thromboembolism in cancer and non-cancer patients: From the COMMAND VTE registry.

BACKGROUND: There is a paucity of data comparing the long-term outcomes after inferior vena cava (IVC) filters placement for patients with acute venous thromboembolism (VTE) between those with and without active cancer. METHODS: In the COMMAND VTE Registry, we evaluated the effects of IVC filter use on the long-term clinical outcomes stratified by the presence and absence of active cancer. RESULTS: Among 2,626 patients with acute symptomatic VTE, there were 604 patients with active cancer, and 2022 patients without active cancer. IVC filters were placed and not retrieved in 455 patients (17%) in the entire cohort, in 150 patients (24.8%) in the active cancer stratum, and in 305 patients (15.1%) in the non-cancer stratum. In the entire cohort, non-retrieved IVC filter placement was not associated with a lower adjusted risk for PE recurrence (HR 0.59, 95% CI 0.30-1.15, P = 0.122), but with an increased adjusted risk for DVT recurrence (HR 2.27, 95% CI 1.43-3.60, P<0.001). In the non-cancer stratum, the non-retrieved IVC filter placement was associated with a decreased risk for PE (HR 0.29, 95% CI 0.09-0.93, P = 0.037), but not with an increased risk for DVT (HR 1.73, 95% CI 0.89-3.38, P = 0.108), while in the active cancer stratum, it was associated with an increased risk for DVT (HR 2.47, 95% CI 1.24-4.91, P = 0.010), but not with a decreased risk for PE (HR 0.82, 95% CI 0.34--1.96, P = 0.650). CONCLUSIONS: There were some differences in the risk-benefit balance between VTE patients with and without active cancer.

Determinants and prognostic implications of instantaneous wave-free ratio in patients with mild to intermediate coronary stenosis: Comparison with those of fractional flow reserve.

The instantaneous wave-free ratio (iFR) is used for assessing the hemodynamic severity of a lesion, as an alternative to the fractional flow reserve (FFR). We evaluated the relationship between iFR and FFR in detail and the clinical significance of iFR in patients with mild to intermediate coronary artery stenosis. We recruited consecutive 323 patients (421 lesions) with lesions exhibiting 30% to 80% diameter stenosis on angiography in whom FFR and iFR were measured. In the total lesions, mean diameter stenosis was 48.6% ± 9.0%, and physiological significance, defined by FFR of 0.80 or less or by iFR of 0.92 or less, was observed in 32.5% or 33.5%, respectively. Mismatch between iFR and FFR was observed in 18.1% of the lesions. Clinical factors did not predict FFR value; however, gender, diabetes mellitus, aortic stenosis, anemia, high-sensitivity CRP value, and renal function predicted iFR value. In multivariate logistic analysis after adjustment for FFR value, gender (p < 0.001), diabetes mellitus (p = 0.005), aortic stenosis (p = 0.016), high-sensitivity CRP (p < 0.001), and renal function (p = 0.003) were all independent predictors of iFR value. In Kaplan-Meier analysis, the baseline iFR predicted the subsequent major cardiovascular events (MACE) (hazard ratio, 2.40; 95% CI, 1.16-4.93; p = 0.018) and the results of the iFR-guided strategy for predicting rates of MACE and myocardial infarction/revascularization were superior to those of the FFR-guided strategy. In conclusion, significant clinical factors predicted iFR value, which affected the prognostic capacity. The iFR-guided strategy may be superior in patients with mild to intermediate stenosis.

Clinical and angiographic factors predicting fractional flow reserve and explaining the visual-functional mismatch in patients with intermediate coronary artery stenosis.

BACKGROUND: Visual-functional mismatch between coronary angiography and fractional flow reserve (FFR) has been reported, and the underlying reason remains poorly understood. Therefore, the relationship between angiographic measurements and FFR was evaluated, and predictors for FFR in intermediate coronary artery stenosis were determined. METHODS: Consecutive 314 patients (405 lesions) with a lesion of 30-80% angiographic diameter stenosis who underwent invasive FFR were recruited. The myocardial area supplied by the coronary artery distal to the stenosis was evaluated using a modified version of the Bypass Angioplasty Revascularization Investigation (BARI) score. Participants underwent follow-up, and major cardiovascular events (MACE), including all-cause death, myocardial infarction (MI), and unplanned revascularization were recorded. RESULTS: Although % diameter stenosis was correlated with FFR (R = 0.279, P < 0.001), diameter stenosis-FFR mismatch was observed in 37.8% of the lesions. Although FFR values were not associated with clinical factors, such as age, sex, and comorbidities, it was correlated with minimal lumen diameter (MLD), diffuse lesion, presence of proximal lesion, and BARI score. In addition, the lesions in left anterior descending (LAD) coronary artery showed low FFR values compared with those in the left circumflex coronary artery or right coronary artery. In multivariate logistic analysis, MLD (ß coefficient = 0.330), diffuse lesion (ß coefficient = -0.266), proximal lesion (ß coefficient = -0.144), BARI score (ß coefficient = -0.219), and LAD lesion (ß coefficient = -0.293) were all independent predictors for FFR value. The estimated FFR value based on these factors showed smaller mismatch and higher sensitivity. No difference was observed in the event rates for MACE and MI or revascularization between the FFR-guided and estimated FFR-guided strategies. CONCLUSIONS: MLD, diffuse lesion, proximal lesion, BARI score, and lesion vessel were independent predictors for FFR in intermediate coronary stenosis. Not only the extent of local lesion stenosis but also the amount of myocardial supply and the lesion location may determine the physiological significance and explain the visual-functional mismatch. The estimation of FFR by these factors may be useful in clinical practice.

Impact of impaired glucose tolerance on clopidogrel response in patients with coronary artery disease.

Although patients with impaired glucose tolerance (IGT) are at increased atherothrombotic risk, it is unclear how antiplatelet drugs act in patients with IGT. The aim of this study was to investigate the pharmacodynamic response to clopidogrel in patients with IGT and insulin resistance (IR). A 75 g oral glucose tolerance test was performed in 65 coronary artery disease (CAD) patients on aspirin and clopidogrel therapy. Platelet function tests were assessed at 3 time-points by light transmittance aggregometry using ADP (5 and 20 µmol/L) stimuli. 30 patients had IGT and 35 normal glucose tolerance (NGT). Among them, 13 patients showed IR. Following ADP stimuli, patients with IGT showed significantly higher maximal platelet aggregation at each time point than those with NGT patients. This resulted in greater high on-treatment platelet reactivity (HPR) rates at each time point in IGT patients (53.3-36.7 vs. 14.3-11.4 %, p < 0.05). A multivariable logistic regression analysis showed that IGT status was the strongest predictor of HPR (odds ratio 7.54, 95 % CI 1.95-29.1, p = 0.003). Following a glucose load, profiles of platelet reactivity varied according to IR status, with minimal changes over time in patients with IR, while there was a significant reduction in the non-IR patients. In aspirin and clopidogrel-treated patients with CAD, IGT is associated with enhanced platelet reactivity and increased rates of HPR compared with NGT patients. These findings suggest the presence of platelet dysfunction in patients with IGT, which may be attributed to the presence of IR.

The kinetics of glomerular deposition of nephritogenic IgA.

Whether IgA nephropathy is attributable to mesangial IgA is unclear as there is no correlation between intensity of deposits and extent of glomerular injury and no clear mechanism explaining how these mesangial deposits induce hematuria and subsequent proteinuria. This hinders the development of a specific therapy. Thus, precise events during deposition still remain clinical challenge to clarify. Since no study assessed induction of IgA nephropathy by nephritogenic IgA, we analyzed sequential events involving nephritogenic IgA from IgA nephropathy-prone mice by real-time imaging systems. Immunofluorescence and electron microscopy showed that serum IgA from susceptible mice had strong affinity to mesangial, subepithelial, and subendothelial lesions, with effacement/actin aggregation in podocytes and arcade formation in endothelial cells. The deposits disappeared 24-h after single IgA injection. The data were supported by a fluorescence molecular tomography system and real-time and 3D in vivo imaging. In vivo imaging showed that IgA from the susceptible mice began depositing along the glomerular capillary from 1 min and accumulated until 2-h on the first stick in a focal and segmental manner. The findings indicate that glomerular IgA depositions in IgAN may be expressed under the balance between deposition and clearance. Since nephritogenic IgA showed mesangial as well as focal and segmental deposition along the capillary with acute cellular activation, all glomerular cellular elements are a plausible target for injury such as hematuria.

Uncoupling of glomerular IgA deposition and disease progression in alymphoplasia mice with IgA nephropathy.

Previous clinical and experimental studies have indicated that cells responsible for IgA nephropathy (IgAN), at least in part, are localized in bone marrow (BM). Indeed, we have demonstrated that murine IgAN can be experimentally reconstituted by bone marrow transplantation (BMT) from IgAN prone mice in not only normal mice, but also in alymphoplasia mice (aly/aly) independent of IgA+ cells homing to mucosa or secondary lymphoid tissues. The objective of the present study was to further assess whether secondary lymph nodes (LN) contribute to the progression of this disease. BM cells from the several lines of IgAN prone mice were transplanted into aly/aly and wild-type mice (B6). Although the transplanted aly/aly showed the same degree of mesangial IgA and IgG deposition and the same serum elevation levels of IgA and IgA-IgG immune-complexes (IC) as B6, even in extent, the progression of glomerular injury was observed only in B6. This uncoupling in aly/aly was associated with a lack of CD4+ T cells and macrophage infiltration, although phlogogenic capacity to nephritogenic IC of renal resident cells was identical between both recipients. It is suggested that secondary LN may be required for the full progression of IgAN after nephritogenic IgA and IgA/IgG IC deposition.

Difference in statin effects on neointimal coverage after implantation of drug-eluting stents.

OBJECTIVE: This study was carried out to examine the difference in effects between rosuvastatin and pravastatin on neointimal formation after the placement of a drug-eluting stent (DES). MATERIALS AND METHODS: Forty patients who underwent placement of a DES in our hospital were prospectively randomized to receive rosuvastatin (n=20) or pravastatin (n=20), and analyzed by optical coherence tomography at the chronic stage. The main outcome measure was comparison of neointimal coverage analyzed at a strut level. RESULTS: A significant reduction in total cholesterol, low-density lipoprotein, and white blood cell count was observed during the study in the rosuvastatin group (total cholesterol, from 4.82±0.90 to 4.43±0.77 mmol/l, P=0.038; low-density lipoprotein, from 2.85±0.76 to 2.34±0.57 mmol/l, P=0.006; white blood cell count, from 5810±1399 to 5355±1257/µl, P=0.048), but not in the pravastatin group. Although not statistically significant, C-reactive protein was lower in the rosuvastatin than in the pravastatin group at the chronic stage (1.14±1.21 vs. 7.67±13.67 mg/l, P=0.051). Malapposed and uncovered struts were significantly less frequent in the rosuvastatin group than in the pravastatin group (malapposed, 0.06 vs. 0.60%, P<0.001; uncovered, 6.49 vs. 11.29%, P<0.001). The difference in uncovered struts was maintained even when stent types were analyzed separately (everolimus-eluting stent, 4.81 vs. 6.21%, P=0.007; sirolimus-eluting stent, 14.40 vs. 20.86%, P<0.001). Comparison of neointimal thickness between the rosuvastatin and the pravastatin groups showed inconsistent results depending on the stent types analyzed. CONCLUSION: Compared with pravastatin, the use of rosuvastatin resulted in lower frequency of uncovered and malapposed struts after the placement of a DES, which might be mediated through improved inflammatory and lipid profiles.

Clinical utility of low-pressure implantation of drug-eluting stent into very small vessels.

BACKGROUND: Although drug-eluting stents (DES) reduce restenosis, the best strategy for DES implantation in small vessels has not been established. PURPOSE: We investigated the clinical usefulness of low-pressure implantation of a 2.5-mm DES for small vessels less than 2.5mm in diameter. METHODS: In 118 patients, a 2.5-mm DES was implanted for small vessels less than 2.5mm in diameter between 2007 and 2009 in our hospital. The patients were divided into two groups by initial deployment pressure: low-pressure (LP; n=46) and nominal-pressure (NP; n=72). RESULTS: Patients with impaired glucose tolerance were more frequent (p=0.02) and the target vessel diameter was significantly smaller (p=0.01) in the LP group than in the NP group. A smaller minimum lumen diameter (MLD) was obtained (LP: 2.22±0.27mm vs. NP: 2.34±0.26mm, p=0.02) after DES implantation with a smaller balloon-to-artery ratio (p=0.03) in the LP group. However, at mid-term follow-up (7.7±3.9 months), MLD (p=0.55) and the binary restenosis rate (LP: 2.6% vs. NP: 11.1%, p=0.12) were not significantly different between the LP and NP groups. Furthermore, by Kaplan-Meier analysis, the incidence of major adverse cardiac events was not different between the groups during the long-term follow-up (32.4±8.6 months). CONCLUSION: The present study indicates that low-pressure implantation of 2.5-mm DES for very small vessels may be feasible with regard to short- and long-term clinical outcomes.

Difference in neointimal coverage at chronic stage between bare metal stent and sirolimus-eluting stent evaluated at stent-strut level by optical coherence tomography.

Compared with the bare metal stent (BMS), suppression of neointimal growth in the sirolimus-eluting stent (SES) reduced restenosis at the cost of more exposed struts that could impose the risk of stent thrombosis. The present study was conducted to analyze neointimal coverage patterns of stents at a strut-level after implantation of BMS or SES with the use of optical coherence tomography (OCT). We enrolled 35 patients and analyzed neointimal coverage of every strut from 41 stents (BMS: n = 8, SES: n = 33) by using OCT at follow-up of the stent implantation. All of the 371 struts from eight BMSs were covered with ≥100 µm of neointima, while 19.8 and 3.5% of 3,478 struts from 33 SESs were uncovered (neointimal thickness of <10 µm) and malapposed, respectively. The histogram of neointimal thickness showed basically normal distribution in BMS but skewed in SES. No regional difference in neointimal thickness was observed in BMS (proximal, 535.7 ± 25.2 µm; body, 532.4 ± 17.0 µm; distal, 485.8 ± 27.0 µm). In SES, however, the body segment showed thinner neointima [median 40 µm (interquartile range (IQR) 10-90 µm)] than proximal [60 µm (IQR 10-140 µm), p < 0.001] or distal [50 µm (IQR 10-110 µm), p < 0.001] segment, while uncovered and malapposed struts were more frequent in the proximal and body segments. In conclusion, SES, compared with BMS, showed more suppressed neointimal growth with regional variation: neointimal thickness was the least in the body part while the ratio of exposed and malapposed struts was minimal in the distal segment. OCT was useful for a strut-level analysis of neointimal coverage over the whole stent.

Reevaluation of the mucosa-bone marrow axis in IgA nephropathy with animal models.

Impaired immune regulation along the 'mucosa-bone marrow axis' has been postulated to play an important role in the pathogenesis of IgA nephropathy (IgAN). Animal models have allowed us to study such changes in detail. Recently, we established several useful animal models, including IgAN-prone mice. Using these animal models, our group is approaching the underlying mechanisms by which bone marrow and mucosal cell interrelate and finally induce this disease. Accumulating evidence from these approaches suggests that there is dysregulation of innate and cellular immunity in IgAN resulting in changes in the mucosal immune system. These changes appear to be closely linked to disruption of mucosal tolerance, resulting in abnormal priming and dissemination of cells to sites such as the bone marrow where they are responsible for synthesis of nephritogenic IgA. Our clinical studies further support these ideas and indicate that the tonsils may be a major mucosal priming site in human IgAN. In addition, our findings also suggest clinical application of nephritogenic IgA (IgA1) as a biological marker and possible future treatment strategies that focus on manipulating the priming and dissemination of these memory cells in order to prevent the appearance of nephritogenic IgA (IgA1) in the systemic compartment.

Roles of bone marrow, mucosa and lymphoid tissues in pathogenesis of murine IgA nephropathy.

Previous studies indicated that bone marrow cells may contribute to the pathogenesis of IgA nephropathy (IgAN). However, the cell types and mechanisms responsible remain unclear. Our recent study showed that 'grouped ddY mice' is a useful model to approach the pathogenesis of IgAN. Moreover, we also reported that bone marrow transplantation (BMT) from the onset mice of this model reconstituted IgAN in healthy recipients with strong Th1-polarization. We aimed to examine the roles of bone marrow (BM) cells, mucosa and lymphoid tissues in IgAN. We employed onset ddY mice and mutant mice lacking all systemic lymph nodes, Payer's patch, isolated lymphoid follicles in the lamina propria (LP) and IgA producing cells. BM cells from the onset mice were transplanted into the mutant and wild type (C57BL/6:B6). After BMT, serum elevation of IgA and IgA(+)B220(-) plasma cells in BM, but not IgA producing cells in LP, were observed in the mutant mice. Although both transplanted mice showed mesangial IgA deposition, glomerular lesions with IgG2a co-deposition were detected only in B6 mice. The present results suggest that glomerular IgA deposition, but not glomerular damage, can be induced by BM-derived or -primed IgA-producing cells independently of priming in mucosa and secondary lymphoid tissues.

[Comparison of prediction equations of glomerular filtration rate in Japanese adults].

OBJECTIVE: Creatinine clearance (Ccr) is widely used for the evaluation of the glomerular filtration rate (GFR). Since the clearance method requires urine collection, formulae for predicting GFR without urine collection have been developed. In the guidelines of the Kidney Disease Outcomes Quality Initiative(K/ DOQI), the formulae developed from the Modification of Diet in Renal Disease Study (MDRD) are recommended for estimating GFR. The objective of the present study is to compare measured Ccr and Ccr estimated by the Cockcroft-Gault, Horio and MDRD equations in Japanese adults. MATERIALS AND METHODS: In 100 inpatients (67 men and 33 women) in this hospital, we evaluated the correlation between measured Ccr derived from 24-hour urinary collections and predicted Ccr or GFR calculated using the Cockcroft-Gault, Horio, and MDRD equations. RESULTS: The equation of linear regression is given as y = 0.8165x+2.1229 (r = 0.9415, p < 0.0001) by the Cockcroft-Gault formula, y = 0.7478x+1.6757 (r = 0.9458, p < 0.0001) by the Horio formula and y = 0.8335x+4.4261 (r = 0.9209, p < 0.0001) by the MDRD formula (y : measured Ccr, x : estimated Ccr or GFR). These predictive formulae demonstrated a strong correlation. CONCLUSION: Although the Cockcroft-Gault formula derived from Japanese patients demonstrated the highest correlation with Ccr, both the Horio formula and the MDRD formula also showed a high correlation. These predictive formulae could be useful for the prediction of Ccr in Japanese patients.

[Internal ophthalmoplegia in acute oropharyngeal palsy with anti-GQ1b and anti-GT1a IgG antibodies].

A patient with acute oropharyngeal palsy associated with internal ophthalmoplegia was reported. A 13-year-old boy had fever and diarrhea for two days. Ten days after resolution of these symptoms, he noticed difficulty in speaking (day 1). Neurological findings on day 4 included bilateral mydriasis, right abducens nerve palsy, nasal voice with absent pharyngeal reflex. Although superficial sensation was preserved, vibratory sensation was reduced in distal limbs. Tendon reflexes were generally absent. Neither ataxia nor dysautonomia was seen. Serum anti-glycolipid antibody assay on day 4 disclosed elevated IgG antibodies to GQ1b and GT1a. His cerebrospinal fluid on day 21 contained 6 mononuclear cells/microl with 137 mg/dl of total protein. Nerve conduction study on day 5 showed minimal sensory nerve involvement. Quantitative sudomotor axon reflex test was normal in the lower extremities. Low dose pilocarpine eyedrops dilated his pupils. Although mild cerebellar-like ataxia appeared on day 5, intravenous immunoglobulin (0.4 g/kg/day for four days) rapidly improved his neurological abnormalities. IgG anti-GQ1b antibody might contribute not only oropharyngeal weakness but also internal ophthalmoplegia in this patient.

A case of primary immunoglobulin light chain amyloidosis with a delayed appearance of Bence Jones protein in urine.

We report here a case of a 58-year-old man who had nephrotic syndrome and immunoglobulin light chain (AL) amyloidosis. This patient underwent a renal biopsy to confirm the diagnosis. Treatment with permanganate before Congo red staining showed systemic secondary amyloidosis (AA) fibrils, which were sensitive to permanganate oxidation. Although this patient was initially diagnosed as having AA amyloidosis, he did not have any chronic inflammatory disease and/or malignancy. The level of amyloid A protein (7.9 microg/mL) in sera was within the normal range (0-8.0 microg/mL). Therefore, we performed an immunostaining of the precursor protein (amino terminus of constant region: kappa and lambda light chains, and AA protein) using duodenal biopsy specimens for a precise diagnosis. Immunostaining was positive for the amino terminus of constant region of the lambda light chain, and negative for the amino terminus of constant region of the kappa light chain and AA protein. No plasma cell proliferation in the bone marrow was observed. We finally diagnosed this patient as having primary AL amyloidosis. It appears that a pathological diagnosis must be performed by immunostaining the precursor proteins with the permanganate digestion technique in tissue of patients with amyloidosis. There were no abnormalities in serum and urine immunoelectrophoresis at the time of renal biopsy in this patient. During the follow-up period, after discharge, Bence Jones protein appeared in the urine, but not in the serum. It is necessary to observe patients with primary AL amyloidosis carefully to determine if they their condition will progress to multiple myeloma.