Association of the PCK2 Gene Polymorphism With New-onset Glucose Intolerance in Japanese Kidney Transplant Recipients.

BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a risk factor for both cardiovascular disease and poor graft survival after kidney transplantation (KTx). In this study, we identified single-nucleotide polymorphisms (SNPs) in genes involved in glucose metabolism and examined the correlation between these SNPs and glucose intolerance after KTx. METHODS: Thirty-eight patients with normal glucose tolerance before KTx were included in this study. Patients with plasma glucose levels of >140 mg/dL at 120 minutes on the 75-g oral glucose tolerance test at 1 year after KTx were classified as having new-onset impaired glucose tolerance (NIGT). We identified 8 SNPs in 7 genes that are involved in glucose metabolism among the patients included in this study, and compared the prevalence rate of NIGT among SNPs in each gene. RESULTS: Of the 38 patients, 11 (28.9%) were diagnosed with NIGT. For rs4982856 in the PCK2 gene, the distribution of genotypes among the total patient population was as follows: T/T, 12 (31.6%); T/C, 22 (57.9%); and C/C, 4 (10.5%). Seven of 11 patients with NIGT had the T/T genotype of rs4982856, whereas only 5 of 27 patients with normal glucose tolerance had this genotype. The T allele frequency of the rs4982856 was significantly higher in the NIGT group than in the normal group (81.8 vs 52.8%, respectively; P = .015). CONCLUSION: Our study indicates that the T allele of the rs4982856 SNP in the PCK2 gene may be a risk factor for glucose intolerance after KTx.

Hypoxia-Inducible Factor-1α Expression in Kidney Transplant Biopsy Specimens After Reperfusion Is Associated With Early Recovery of Graft Function After Cadaveric Kidney Transplantation.

BACKGROUND: Ischemia/reperfusion injury during kidney transplantation (KTx) delays allograft recovery. Hypoxia-inducible factor-1α (HIF-1α) is the key regulator of the protective response to ischemia/reperfusion injury. We evaluated the impact of the HIF-1α signaling pathway on allograft recovery during cadaveric KTx. METHODS: Between 1996 and 2015, 46 patients underwent cadaveric KTx. The expression levels of HIF-1α-related proteins, including phosphoinositide 3-kinase, phosphorylated (p)-Akt, p-mammalian target of rapamycin, p-Eukaryotic translation initiation factor 4E, p-S6 ribosomal protein, and HIF-1α, were immunohistochemically evaluated and semi-quantitatively scored in graft biopsy specimens after 1 hour of revascularization. Ten kidney biopsy specimens collected during donor nephrectomy for living KTx were used as controls. Delayed graft function (DGF) was defined as the need for dialysis within 1 week of KTx. We compared the staining scores of each protein and several clinical parameters between patients with and those without DGF. RESULTS: Expression levels of all six proteins in specimens after revasculization were elevated compared with those in controls. Thirty-five patients had DGF. Expression levels of PI3K, p-AKT, p-mTOR, p-eIF4E, and HIF-1α were significantly higher in patients without DGF than in those with DGF. Univariate analysis identified expression levels of p-Akt, p-S6, and HIF-1α, in addition to donor type (heart beating/non-heart beating), cold ischemic time, and donor age as significant predictors of DGF. Of these, only expression levels of HIF-1α and donor type were independently associated with DGF in multivariate analysis. CONCLUSIONS: Up-regulation of HIF-1α in allografts after reperfusion may be a predictor of early recovery after cadaveric KTx.

Incidence and Risk Factors of Persistent Hyperparathyroidism After Kidney Transplantation.

Persistent hyperparathyroidism after kidney transplantation is related to graft function, but pre-transplantation risk factors of persistent hyperparathyroidism have not been evaluated in detail. We enrolled 86 patients who had undergone kidney transplantation between 2008 and 2014. Nine patients showed persistent hyperparathyroidism characterized by the following: 1) serum parathyroid hormone levels >65 pg/mL and serum calcium levels >10.5 mg/dL at 1 year after kidney transplantation; 2) parathyroidectomy after kidney transplantation; and 3) reintroduction of cinacalcet after kidney transplantation. Compared with other patients, these 9 patients had significantly longer duration of dialysis therapy (186 ± 74 mo vs 57 ± 78 mo) and more frequent treatment with cinacalcet during dialysis (89% vs 12%). Multivariate analysis showed that dialysis vintage, calcium phosphate products, and cinacalcet use before kidney transplantation were independent risk factors of persistent hyperparathyroidism after kidney transplantation. A receiver operating characteristic curve showed 72 months as the cutoff value of dialysis vintage and 55 as the cutoff value of calcium phosphate products. In conclusion, dialysis vintage >6 years, calcium phosphate products >55 (mg/dL)2, and cinacalcet use before kidney transplantation are strong predictors of persistent hyperparathyroidism. High-risk patients should be evaluated for parathyroid enlargement, and parathyroidectomy must be considered before kidney transplantation.

Pre-Transplant Erythropoiesis-Stimulating Agent Hypo-Responsiveness and Post-Transplant Anemia.

BACKGROUND: At the time of kidney transplantation (KT), almost all patients have anemia caused by low levels of endogenous erythropoietin (EPO), along with several other factors. After KT, anemia improves because of secretion of EPO from the allograft. But some recipients have persistent anemia. Whether or not erythropoiesis-stimulating agent (ESA) hypo-responsiveness before KT affects post-transplant anemia (PTA) remains unknown. METHODS: Sixty-eight patients received KT between January 2007 and July 2012 through the Department of Urology at Kobe University Hospital, and 35 of these patients were enrolled. Exclusion criteria included age <18 years, unknown ESA dosage at transplantation, ESA start within 1 year after transplantation, and other criteria. We evaluated post-transplant hemoglobin (Hb) levels from the pre-transplant ESA responsive index (ERI): pre-transplant ESA dosage/Hb × body weight at 1 year after transplantation. RESULTS: The mean (± SD) Hb of all patients rose from 11.3 ± 1.0 mg/dL to 12.7 ± 1.4 mg/dL at 1 year after transplantation (P < .01). The pre-transplant low ERI group (<10) showed significantly higher hemoglobin levels compared with the pre-transplant high ERI group (≥ 10; 12.9 ± 1.14 mg/dL versus 11.8 ± 1.76 mg/dL, respectively; P = .03). CONCLUSIONS: ESA hypo-responsiveness before KT carried over after KT. Low pre-transplant ERI might be a sentinel marker for PTA.

Usefulness of three-dimensional computerized tomographic volumetry for determining split renal function in donors for living-related kidney transplantation.

BACKGROUND: In living-related kidney transplantation, it is important to spare the superior kidney for the donor if there is a significant difference in split renal function. We have been using renal scintigraphy to decide which kidney to be donated. Recently, we used data regarding kidney volume and maximum area in the frontal plane of the 3-dimensional computerized tomography (3DCT) image of the kidney. We evaluated the validity of these parameters for estimating split renal function. METHODS: We calculated the ratio of right kidney volume (VOL-ratio) and maximum area in the frontal plane of the kidney (AREA-ratio) with the use of 3DCT and examined the correlation between these 2 parameters and the ratio of right kidney estimated renal plasma flow (ERPF-ratio) calculated with the use of technetium-99m mercaptoacetyltriglycine ((99m)Tc-MAG3) renal scintigraphy. Forty-six donors for living-related kidney transplantation were evaluated. Their mean age was 53 years; there were 14 male and 32 female donors. RESULTS: Correlation coefficients between VOL-ratio and ERPF-ratio and between AREA-ratio and ERPF-ratio were 0.441 and 0.471, respectively (P = .002; P = .001). Bland-Altman analysis confirmed that the majority of difference scores between VOL-ratio-ERPF-ratio and AREA-ratio-ERPF-ratio were within the 95% confidence interval of the differences. The differences between VOL-ratio-ERPF-ratio and AREA-ratio-ERPF-ratio were (mean ± 1.96SD) 1.17 ± 6.04% and -0.82 ± 6.09%, respectively. It seemed that the distribution of AREA-ratio-ERPF-ratio was less biased than that of VOL-ratio-ERPF-ratio. CONCLUSIONS: The discrepancy between the ratio of kidney volume and the maximum area in the frontal plane of the kidney may have been due to the rotation of the kidney. The ratio of ERPF obtained with the use of renal scintigraphy approximates not only the ratio of kidney volume but also the ratio of maximum area in the frontal plane of the kidney. Thus, our findings suggest that the use of (99m)Tc-MAG3 renal scintigraphy alone may underestimate the function of a rotated kidney.

The impact of donor factors on early graft function in kidney transplantation from donation after cardiac death.

Donation after cardiac death (DCD) has the potential to significantly increase the number of organ donors. In this study, we investigate the influence of several donor parameters on the early graft function in kidney transplantation from DCD donors. We performed 58 kidney transplantations from DCD donors. Recipients were divided into 2 groups according to their graft function: normal graft function (NGF), patients who became be free of hemodialysis within 14 days post-transplantation) and delayed graft function (DGF) group, patients who required hemodialysis for longer than 15 days after transplantation). We compared donor age, sex, cause of death, warm and total ischemic time, duration of anuria (urine volume < 10 mL/h), and low blood pressure (systolic blood pressure < 60 mm Hg), usage of catecholamine and vasopressin, serum creatinine on the day of admission and graft retrieval, serum sodium concentration, and body temperature between 2 groups. The number of recipients in NGF and DGF group was 41 and 17. Univariate analysis revealed that duration of anuria (<24 vs ≥ 24 hours) and usage of catecholamine significantly influenced graft function. Duration of anuria was an independent risk factor for early graft function by multivariate analysis. In cadaveric kidney transplantation from DCD donors, there was a trend to poorer early graft function with donors who suffered from anuria for longer than 24 hours before kidney retrieval.

Excellent results of immunocomplex capture fluorescence analysis-I for cross-match test in renal transplantation.

A flow cytometry cross-match (FCXM) test is the gold standard for detection of human leukocyte antigen (HLA) antibodies in renal transplantation because of its high sensitivity. However, this technique can produce false-positive results when non-HLA antibodies or low-titer donor-specific antibodies (DSA) are detected. To determine the clinical relevance of the recently introduced novel cross-match test termed immunocomplex capture fluorescence analysis (ICFA), we retrospectively compared the results of ICFA and FCXM, including a single-antigen bead test for detection of DSA in renal transplant recipients. We found a correlation of 71.4% (235/329) between the results of ICFA-I and FCXM-T, whereas that between ICFA-II and FCXM-B was 41.1% (134/326). Ninety-four patients were ICFA-I negative and FCXM-T positive, and 188 were ICFA-II negative and FCXM-B positive, whereas 46.8% (44/94) and 61.7% (116/188) were found to be DSA-I and DSA-II negative, respectively, which classified them into the non-HLA antibody and low-titer DSA groups, respectively. The mean value of molecules of equivalent soluble fluorochrome for DSA-I was 22,994 in the ICFA-I-positive group, which was significantly higher than 2117 in the negative group (P < .0001), whereas there was no significant difference for DSA-II between the ICFA-II-positive and ICFA-II-negative groups. Graft survival in the ICFA-I-negative group was significantly higher than that in the ICFA-I-positive group (P = .0058). Our results indicate that ICFA-I does not respond to non-HLA antibodies or low-titer DSA, which have influence on graft survival. Therefore, this novel hybrid test, which combines cross-match testing and HLA antibody detection functions, may be useful for clinical pretransplantation evaluation of renal transplantation patients.

A prospective randomized comparison of diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy.

The aim of this study is to elucidate the diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy for prostate cancer. We prospectively randomized 200 consecutive men into two groups to undergo systematic prostate biopsy. Overall positivity for cancer was similar (47% by transperineal and 53% by transrectal; P=0.480). However, in case with 'gray zone' PSA (from 4.1 to 10.0 ng/ml), significantly more cores were positive when approach was transperineal, especially among transition zone cores. Therefore, urologist preferences are sufficient for choosing an approach, except for a possible small advantage of transperineal biopsy when PSA is in gray zone.

Expression of leptin and leptin receptor in the testis of fertile and infertile patients.

The aim of our study was to investigate the relationships between the expression of leptin, leptin receptor in the testis and spermatogenesis, and testosterone (T) concentration in infertile men. Testicular tissue samples were collected from the testes of five fertile volunteers, eight patients with obstructive azoospermia (OA), six patients with Sertoli cell-only syndrome (SCO) and 32 oligospermic patients with varicocele testis. In testicular tissue, leptin and leptin receptor were identified by staining with polyclonal antibodies. Serum follicle stimulating hormone, lutenising hormone (LH), and T were determined by chemiluminescence assays. Leptin was expressed on germ cells, mainly on spermatocytes. The ratio of immunostained germ cells to total germ cells was inversely correlated with the concentration of T (r = -0.32, P = 0.01), sperm concentration (r = -0.51, P = 0.002) and Johnsen's score (r = -0.44,P = 0.005). In contrast, leptin receptor immunostained cells were found in the interstitium, primarily in Leydig cells. Leptin receptor expression on Leydig cells was inversely correlated with serum T concentration (r = -0.50, P < 0.001). The dysfunction of spermatogenesis is associated with an increase in leptin and leptin receptor expression in the testis.

Erectile function after brachytherapy with external beam radiation for prostate cancer.

The effect of therapeutic modalities on sexual potency is an important consideration for patients choosing a treatment for prostate cancer. We assessed erectile function after iridium-192 (1r-192) high-dose rate (HDR) brachytherapy with external beam radiation therapy (EBRT), and examined the efficacy of sildenafil after this treatment. Forty-two prostate cancer patients (T1c to T3bN0M0) were treated with 22Gy HDR brachytherapy with 36.8Gy EBRT without neoadjuvant hormone therapy. Erectile function was assessed using a 5-item version of the International Index of Erectile Function questionnaire (IIEF-5), pre, 3 and 12 months after treatment, Potency was defined as an IIEF-5 score > or = 11. Ten patients with potency before HDR brachytherapy with EBRT with or without neoadjuvant hormone therapy requested Sildenafil 3 months after treatment. The mean IIEF-5 score of all patients was 10.5 +/- 8.5, 4.5 +/- 5.3 (p < 0.001), and 3.8 +/- 4.7 (p < 0.001), pre, 3 and 12 months after treatment, respectively. Seventeen (40.4%) patients were potent before treatment. The mean IIEF-5 score of those patients was 15.8 +/- 3.2, 9.6 +/- 5.1 (p = 0.04), and 11.3 +/- 6.1 (p = 0.06), pre, 3 and 12 months after treatment, respectively. Ten of 17 (58.8%) patients maintained their potency 12 months after treatment. In 10 patients with potency before treatment who were treated with sildenafil, the mean IIEF-5 score increased from 6.2 +/- 3.5 at 3 months to 13.6 +/- 5.1 (p < 0.001) at 12 months after treatment. Eight of 10 (80%) patients treated with sildenafil had recovered 12 months after treatment. HDR brachytherapy with EBRT can be performed with favorable results for maintaining potency.

Significance of cancer detection in the anterior lateral horn on systematic prostate biopsy: the effect on pathological findings of radical prostatectomy specimens.

OBJECTIVE: To clarify the significance of cancer detection in the anterior lateral horn (ALH) on systematic prostate biopsy in relation to its effect on the pathological findings from retropubic radical prostatectomy (RRP) specimens. PATIENTS AND METHODS: The study included 84 consecutive patients who underwent RRP at our institution between January 1999 and December 2002, after being diagnosed as having prostate cancer, based on systematic prostate biopsies that included the areas taken by standard sextant biopsies and the bilateral ALHs. Several clinicopathological factors of these patients were analysed in relation to the presence or absence of cancer in the ALH on systematic biopsy. RESULTS: Of the 84 patients, cancer was detected in the ALH in 44 (group A), but not in the remaining 40 (group B). There were no significant differences in age, preoperative serum prostate-specific antigen level, or prostate volume between the groups. However, the incidence of bilateral positive cores and the percentage of positive biopsy cores in group A were significantly higher than those in group B. Pathological examinations of RRP specimens showed no significant differences in the incidence of lymphatic invasion, vascular invasion and perineural invasion, or Gleason score between the groups, but group A had a significantly larger tumour volume and higher incidence of extraprostatic disease than group B. CONCLUSIONS: Despite similar biological tumour characteristics and irrespective of the cancer location in the ALH, advanced and extensive disease frequently involves the ALH. Therefore, more aggressive treatment should be considered if cancer is detected in the ALH by systematic prostate biopsy.

Significance of early biopsy in pediatric kidney transplantation.

Long-term renal allograft survival is limited mainly by the progressive process termed chronic allograft nephropathy (CAN) or chronic rejection. A pathological feature of CAN is characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)-beta(1) plays an important role in fibrogenesis. We investigated whether the degree of TGF-beta(1) expression in early biopsy specimens routinely obtained from stable allografts at 100 days could predict fibrosis and graft dysfunction in the late phase by immunohistochemistry. Patients were children with a graft from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF-beta(1) in the graft at 100 days using LC antibody (LC) for intracellular TGF-beta(1) and CC antibody (CC) for extracellular TGF-beta(1). We used the change in creatinine clearance between 100 days and 3 years after transplantation (Delta Ccr) as an index of long-term graft function. Image analysis was used to calculate the relative area involved by interstitial fibrosis in trichrome-stained sections of graft biopsy specimens at 100 days and 3 years, designating the change as Delta FI. Delta Ccr was - 4.2 +/- 9.4 mL/min in subjects with minimal early immunoreactivity for CC and - 20.5 +/- 5.9 mL/min in subjects with strong reactivity (p < 0.05). Delta Ccr was - 14.5 +/- 18.6 mL/min in subjects with minimal early immunoreactivity for LC and - 11.7 +/- 12.8 mL/min in those with strong reactivity. Delta FI in subjects with minimal CC reactivity (1.28 +/- 4.11 %) tended to be lower than in subjects with strong reactivity (8.45 +/- 15.47 %). Neither fibrosis at 100 days nor Delta FI differed between subjects with minimal and strong LC reactivity. Thus, extracellular TGF-beta(1) expression in grafts at 100 days after transplantation has an influence on long-term graft function and tends to be associated with increased graft fibrosis at 3 years.

Transforming growth factor-beta1 expression in early biopsy specimen predicts long-term graft function following pediatric renal transplantation.

The main cause of late graft loss or declining long-term graft function is chronic allograft nephropathy (CAN), characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)-beta1 plays a key role in fibrogenesis. We immunohistochemically investigated whether the degree of TGF-beta1 expression in early biopsy specimens routinely obtained from stable allografts at 100 d could predict fibrosis and graft dysfunction in the late phase. Patients were children with grafts from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF-beta1 in the graft using LC antibody (LC) for intracellular TGF-beta1 and CC antibody (CC) for extracellular TGF-beta1. The change in creatinine clearance between 100 d and 3 yr after transplantation (DeltaCcr) was used as an index of long-term graft function. We also used image analysis to calculate the relative area involved by interstitial fibrosis in the trichrome-stained section of graft biopsy specimens at 100 d and 3 yr, designating the change as DeltaFI. DeltaCcr was -4.2+/-9.4 mL/min in subjects with minimal early immunoreactivity for CC and -20.5+/-15.9 mL/min in subjects with strong reactivity (p<0.05). DeltaCcr was -14.5+/-18.6 mL/min in subjects with minimal early immunoreactivity for LC and -11.7+/-12.8 mL/min in those with strong reactivity. DeltaFI in subjects with minimal CC reactivity (1.28+/-4.11%) tended to be lower than that in subjects with strong reactivity (8.45+/-15.47%). Neither fibrosis at 100 d nor DeltaFI differed between subjects with minimal and strong LC reactivity. Thus, strong extracellular TGF-beta1 expression in grafts at 100 d after transplantation is associated with a long-term decline in graft function and tends to be associated with increased graft fibrosis at 3 yr.

A novel antireflux uretero-ileal anastomosis for urinary diversion: an experimental study.

OBJECTIVES: To assess a new antireflux valve technique in a dog model of urinary diversion, and thus provide a reliable and easily constructed antireflux system for an ileal reservoir. MATERIALS AND METHODS: In five female beagle dogs, 3 cm of ileum were intussuscepted into the reservoir formed using the adjacent 10 cm of ileum. The intussuscepted ileum was sutured to the reservoir wall after stripping the mucosa of the reservoir in a trapezoidal zone opposite the similarly stripped mucosa of the intussuscepted ileum, to avoid dessusception. After the distal 4 cm of the ureters was united and pulled through the intussuscepted segment of ileum, the combined distal ureter was sutured to the labial edge of the intussuscepted segment. Finally, the reservoir was anastomosed to the bladder as an enterocystoplasty. Dogs were evaluated by ascending cystography and intravenous pyelography at 1 and 6 months. The valve and upper urinary tract were evaluated histopathologically at 6 months. RESULTS: In all dogs the antireflux system remained intact and prevented reflux. The intussuscepted ileum was firmly attached to the reservoir wall and the submucosa of each segment was united. The upper urinary tract was normal with no ureteric stenosis. Histopathologically, the ureter was surrounded by intact ileal serosa and showed no inflammation or scarring. CONCLUSIONS: The very short ileal segment required and the firm attachment of the constructed valve to the reservoir were the advantages of this practical and reliable new antireflux system.

Efficacy of prophylactic aerosol amphotericin B lipid complex in a rat model of pulmonary aspergillosis.

Invasive pulmonary aspergillosis remains an important cause of morbidity and mortality among transplant recipients and patients receiving cancer chemotherapy. The lipid-associated formulation of amphotericin B (AmB), AmB lipid complex (ABLC), was evaluated for its prophylactic efficacy when it was administered as an aerosol in a rat model of pulmonary aspergillosis. Aerosol ABLC (aero-ABLC), in doses from 0.4 to 1.6 mg/kg of body weight given 2 days before infection, significantly delayed mortality compared to the mortality of rats given placebo (P < 0.001). At day 10 postinfection, 50% of rats in the 0.4-mg/kg group and 75% of rats in the 1.6-mg/kg group were alive, while all control animals had died. In a second trial aero-ABLC was more effective than an equivalent dose of aerosol AmB (aero-AmB) in prolonging survival, with 100% survival at day 14 postinfection in the ABLC group, compared to 62.5% survival in the AmB group. Mean concentrations of AmB in lungs were 3.7 times higher at day 1 (P < 0.002) and almost six times higher at day 7 (P < 0.001) after treatment with aero-ABLC than after treatment with a similar dose of aero-AmB. We conclude that aero-ABLC provided higher and more prolonged levels of the parent compound in the lungs than aero-AmB and was more effective in delaying mortality from aspergillosis in this model.

Prevalence of severity of hypoxemia following clinical voluntary hyperventilation.

The voluntary hyperventilation (VHV) test is used in many clinical examinations. However, arterial hypoxemia following a clinical VHV test is not a well-studied phenomenon. We analyzed the arterial blood gases (ABGs) of 61 patients during a VHV test. The ABG were taken prior to (PaO2-Prior), immediately following (PaO2-Immediate), and 5 min after (PaO2-After) the VHV test. The patients' average PaO2 rose significantly (p < 0.0001) from the PaO2-Prior (88 +/- 8 mm Hg; mean +/- SD) to the PaO2-Immediate (118 +/- 13 mm Hg) and then dropped significantly (p < 0.0001) to the PaO2-After (74 +/- 16 mm Hg). Two of the 20 patients who experienced an angina pectoris attack (AP(+)) following the VHV test showed severe arterial hypoxemia (PaO2-After < 60 mm Hg), whereas 9 of the 41 patients who did not experience an angina pectoris attack (AP(-)) showed a PaO2-After < 60 mm Hg. The PaO2-After did not correlate with the PaO2-Prior. The decrease in the PaO2-Prior to After did not correlate significantly with the left ventricular ejection fraction rate (n = 58, r = 0.18, not significant). However, the decrease in the PaO2-Prior to After correlated well with the degree of recovery of the PaCO2 following the VHV test (r = -0.69, p < 0.0001). The age, gender ratio, changes in arterial blood gases, number of patients who experienced PaO2-After < 60 mm Hg, and left-ventricular ejection fraction rate were not significantly different between the AP(-) and AP(+) groups. Posthyperventilation hypoxemia developed frequently following the VHV test during coronary angiography. Although this arterial hypoxemia was not directly correlated with the occurrence of AP attacks following VHV in this study, continuous SaO2 monitoring is recommended whenever a VHV test is used as a diagnostic technique to avoid the potentially deleterious effects of arterial hypoxemia.

Intravenous dopexamine in the treatment of acute congestive heart failure: results of a multicenter, double-blind, placebo-controlled withdrawal study.

Acute hemodynamic effects of intravenous infusion of dopexamine were evaluated by a placebo-controlled withdrawal study in patients with acute congestive heart failure. Twenty patients were enrolled at 10 centers in Japan. All patients had a pulmonary capillary or diastolic pressure of 15 mmHg or greater and a cardiac index of 2.5 l/min/m2 or less. Phase I: Intravenous dopexamine was introduced in a single-blind, uncontrolled fashion at the rate of 0.5 micrograms/kg/min and was titrated up to achieve a 30% or more increase in the cardiac index. Two patients withdrew from the study due to sinus tachycardia and ventricular ectopy or exacerbation of heart failure. Phase II: The remaining 18 responders who were free of limiting side effects were randomized in double-blind fashion to continue dopexamine or to switch to placebo for an additional 60 minutes. At the end of phase II, the hemodynamic improvement obtained in phase I of the study disappeared completely after substitution of placebo but was maintained in dopexamine-treated patients. Our findings suggest that dopexamine, when given in appropriate doses to selected patients, shows balanced vasodilator action suitable for the treatment of acute congestive heart failure.

Ability of non-cyclic oligosaccharides to form molecular complexes and its use for chiral separation by capillary zone electrophoresis.

The binding constants (K) for complexation of the phenyl acetates with linear alpha-1,4-linked dextrins have been determined from the kinetics of the hydrolyses of the esters. The K value tends to increase with increasing the number of the glucopyranose units, suggesting hydrophobic interaction as a binding force. The weak ability of the linear dextrins to form the molecular complexes makes it possible to separate the enantiomers of binaphthyl derivatives such as 1,1'-binaphthyl-2,2'-dicarboxylic acid, 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate and 2,2'-dihydroxy-1,1'-binaphthyl-3,3'-dicarboxylic acid in their anionic forms. Hydrogen bonding as well as hydrophobic interaction is suggested as an essential force for enantioselective complexation between saccharide and anionic binaphthyl.