Carnitine for Body Composition in Hemodialysis Patients

Background: Authors and colleagues have continued clinical research for hemodialysis patients. Currently, a pilot study presents intervention of carnitine for changes of the body composition. Subjects and Methods: Subjects were six patients on hemodialysis with intervention of carnitine (group 1). Average data were 74.3 years, 65.4 kg, 22.6 in BMI. As levocarnitine, L-Cartin FF injection 1000 mg was administered three times a week for six months. Group 2 has six control patients for age-, sex-, body weight, BMI-matched (group 2). Body composition of muscle and fat tissues were measured by InBody 770 on 0 and 6 months. Results: In group 1, muscle volume and skeletal muscle showed increasing tendency without statistical significance. In contrast, there were significant decreases of body fat volume (22.3 kg vs 20.5 kg, 39.0% vs 35.8%) (p<0.05). No significant differences were found in hemoglobin, total protein, albumin and Cardio-Thoracic Ratio (CTR) of chest X-ray. Group 2 showed no significant changes. Discussion and Conclusion: Hemodialysis patients often have muscular reduction. Previous reports showed improved lean body mass by carnitine administration, which may support our result. These results from current pilot study would be expected to become useful reference data in the pathophysiological investigation in patients on hemodialysis

Investigation of Nerve Conduction in Patients with Diabetes and/or Hemodialysis

Diabetic peripheral neuropathy (DPN) has been clinically important, and nerve conduction studies (NCS) have been performed with rather complexity and high cost. By advances in technology, simple and useful DPN-Check device was developed obtaining NCS data as sural nerve conduction velocity (SNCV) and sural nerve action potential (SNAP). We enrolled 52 subjects classified into 4 groups according to the presence of hemodialysis (HD) and diabetes mellitus (DM) as follows: HD (+), DM (+) in group 1, HD (+), DM (-) in group 2, HD (-), DM (+) in group 3 and healthy controls in group 4. Average age was similar from 68 to 74 years in 4 groups. Median value of SNCV was 31, 48, 49, 54 m/sec, and median value of SNAP was 3, 9, 6, 22 μV, respectively, in 4 groups. These results might suggest some relationship between impaired states of HD and DM, and would become fundamental data for pathophysiological investigation of peripheral neuropathy of HD and/or DM in the future

Investigation of Nerve Conduction in Patients with Diabetes and/or Hemodialysis

Diabetic peripheral neuropathy (DPN) has been clinically important, and nerve conduction studies (NCS) have been performed with rather complexity and high cost. By advances in technology, simple and useful DPN-Check device was developed obtaining NCS data as sural nerve conduction velocity (SNCV) and sural nerve action potential (SNAP). We enrolled 52 subjects classified into 4 groups according to the presence of hemodialysis (HD) and diabetes mellitus (DM) as follows: HD (+), DM (+) in group 1, HD (+), DM (-) in group 2, HD (-), DM (+) in group 3 and healthy controls in group 4. Average age was similar from 68 to 74 years in 4 groups. Median value of SNCV was 31, 48, 49, 54 m/sec, and median value of SNAP was 3, 9, 6, 22 μV, respectively, in 4 groups. These results might suggest some relationship between impaired states of HD and DM, and would become fundamental data for pathophysiological investigation of peripheral neuropathy of HD and/or DM in the future

Influence of Diabetes and Hemodialysis Against Nerve Conduction Studies

Background: Diabetic peripheral neuropathy (DPN) has been prevalent and discussed, and nerve conduction studies (NCS) has been continued. We have checked NCS using recently introduced useful DPN-Check device. Subjects and Methods: The subjects were 66 patients (pts) classified into 4 groups according to existence of diabetes mellitus (DM) and hemodialysis (HD); Group1: DM (+), HD (+) in 15 pts, group 2: DM (-), HD (+) in 15 pts, group 3: DM (+), HD (-) in 20 pts, group 4: 16 healthy controls. Methods included measurements of sural nerve conduction velocity (SNCV) and sural nerve action potential (SNAP) using HDN-1000. Results: Average age in each group was 64.4 years to 72.6 years. SNCV value of 4 group in average was 37.1 m/sec, 46.3 m/sec, 49.3 m/sec, 53.2 m/sec, respectively, and value of group 1 was significantly lower than those of group 2,3,4 (p<0.01). Similarly, average SNAP was 4.1 μV, 8.7 μV, 8.0 μV, 21.6 μV, respectively, and group 1,2,3 were significantly lower than group 4 (p<0.01). There was significant correlation between SNCV and SNAP in all subjects (p<0.01). Significant correlations were shown between DM duration and SNCV, and DM duration and SNAP (p<0.01). Discussion and Conclusion: SNCV and SNAP were measured successfully and easily by HDN-1000, indicating clinical availability. Obtained data suggested that 1) SNCV is not significantly decreased due to only uremic neuropathy, 2) SNCV is significantly decreased in patients with both HD and DM, 3) SNAP is significantly decreased in patents with DM for years and 4) SNAP would be remarkably decreased when HD is in addition to DM. These results would become the basal data of future NCS for DM and HD

J wave due to diagonal branch ischemia

The culprit lesion of acute myocardial infarction could be predicted by electrocardiogram findings. However, we experienced some cases with coronary angiographic finding in the area of ST-T elevation that was different from that predicted. The lambda-like J wave could be caused by ischemia although the mechanism has not been fully elucidated. We report a case of acute myocardial infarction that showed discrepancy between ST-T elevation with lambda-like ischemic J wave in a broad area and coronary angiographical finding of diagonal branch occlusion

シロリムス ヨウシュツ ステント リュウチ 7ネンゴ ニ ハジメテ ゾウエイザイ ステント シュウイ シミダシゾウ オ ミトメタ イチレイ

A 74-year-old man who had a history of percutaneous coronary intervention ［left anterior descending coronary artery ＃6‐7, sirolimus eluting stent （SES） （Cypher stent,3.0×18mm）, left circumflex coronary artery ＃13, SES （Cypher stent, 2.5×23mm）］ for angina pectoris experienced chest pain on effort after seven years from the coronary intervention. He was introduced to our hospital and coronary angiography revealed late acquired peri-stent contrast staining （PSS）, which is defined as an angiographical finding of contrast medium stain outside the stent being ＞20％ of the stent diameter, in the SES of the left anterior descending artery. Drug-eluting stent （DES） significantly inhibits neointimal proliferation, thereby significantly reducing in-stent restenosis. However, the risk of very late stent thrombosis has become a major problem after the DES implantation against the bare-metal stent implantation. PSS has been reported that PSS after SES implantation could predict late stent thrombosis and incomplete stent apposition of the lesion with PSS. In this case, PSS was pointed out for the first time in seven years after SES implantation nevertheless it did not be pointed out in three years. The mechanism and prognosis of PSS is unclear. But, we found the increase in local coagulation at the coronary artery in this case and the degree of prothrombin fragment F1＋2, one of the coagulation marker, was greater in seven years after SES implantation than in three years. We thought these findings might reflect that PSS after SES implantation was associated with very late stent thrombosis. So we started the dual antiplatelet therapy for the prevention of stent thrombosis. Careful long-term observation might be recommended in patients with late acquired PSS and elevated local coagulation response following SES implantation

Pharmacogenomic–pharmacokinetic study of selective estrogen-receptor modulators with intra-patient dose escalation in breast cancer

BackgroundAn association between CYP2D6 polymorphisms and tamoxifen (TAM) efficacy has not been confirmed, partly due to unreliable prediction of active metabolite exposure solely by CYP2D6 activity. The efficacy of TAM dose escalation appears limited in poor TAM metabolizers. Since the chlorine atom on the side chain of toremifene (TOR) prevents 4-hydroxylation by CYP2D6, its contribution to active conversion of TOR is minor. We examined the role of TOR and its dose escalation among poor TAM metabolizers.MethodsThe pharmacokinetics (PK) and pharmacogenomics (PGx) of TAM and TOR were studied. Correlation between PK and CYP2D6 inhibitor use, smoking status, and PGx were examined by regression analysis. For patients showing low endoxifen levels, an intra-patient dose escalation of TOR was conducted, and TOR was increased from 40 to 120 mg for ≥ 24 weeks with PK sampling. Total activity was calculated as the sum of the concentration of each active metabolite adjusted by their respective in vitro activities.ResultsFifty and 11 of the 273 participating patients had endoxifen levels < 15 and < 7.5 ng/mL, respectively. The CYP2D6 genotype was the major determinant for TAM activity (p < 0.01). Smoking status (p = 0.07) and the CYP2C19 phenotype (p = 0.07), but not the CYP2D6 genotype (p = 0.61), showed marginally significant effects on TOR activity. TOR activity increased significantly with dose escalation, even among poor TAM metabolizers, and was maintained for ≥ 24 weeks.ConclusionTOR might be a valid alternative to TAM in patients predicted to be poor TAM metabolizers

Preload stress echocardiography for heart failure

Aim: To improve the prognosis of patients with heart failure, risk stratification in their early stage is important. We assessed whether the change in transmitral flow (TMF) velocity pattern during preload augmentation can predict future hemodynamic worsening in early-stage heart failure patients with impaired relaxation TMF pattern. Methods: We designed a prospective cohort study that included 155 consecutive patients with impaired relaxation (IR) pattern at rest. Preload stress echocardiography was achieved using leg positive pressure (LPP), and changes of TMF pattern during the LPP was observed during baseline echocardiographic examination. The patients whose TMF pattern developed to pseudonormal (PN) pattern throughout the study period were classified into the change to PN group, and patients whose TMF pattern stayed in IR pattern were classified into the stay in IR group. Results: The median follow-up period was 17 months. The average age was 68 ± 11 years old, and 97 patients (63%) were male. Among 155 patients, 27 were classified into the change to PN group. A Cox proportional hazard analysis confirmed that the change in the peak atrial systolic TMF velocity during the LPP (ΔA, hazard ratio = 0.58 per 1SD; 95% CI = 0.39 - 0.88, P = 0.010) was the powerful independent predictor of change into PN pattern. Kaplan-Meier analysis revealed that the patients with ΔA ≤ -7 cm/s had more likely to develop into PN pattern than patients with ΔA > -7 cm/s (P = 0.001). Conclusions: Evaluation of a response in TMF during the LPP might provide an incremental diagnostic value to detect future overt heart failure in patients with early-stage heart failure