Diabetic peripheral neuropathy and prevalence of erectile dysfunction in Japanese patients aged <65 years with type 2 diabetes mellitus: The Dogo Study.

Only limited epidemiological evidence exists regarding the relationship between diabetic neuropathy and erectile dysfunction (ED) among Japanese patients with type 2 diabetes mellitus. To investigate the relationship between diabetic neuropathy and ED among Japanese patients with type 2 diabetes mellitus, a multicenter cross-sectional study was conducted in 287 male Japanese patients with type 2 diabetes mellitus, age (19-65 years). Diabetic neuropathy was diagnosed if the patients showed two or more of the following three characteristics: neuropathic symptoms, decreased or disappeared Achilles tendon reflex and/or abnormal vibration perception. ED, moderate to severe ED, and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. The prevalence values of diabetic neuropathy and severe ED were 47.0 and 39.0%, respectively. Diabetic neuropathy was independently positively associated with severe ED, but not ED and moderate ED: the adjusted odds ratio was 1.90 (95% confidence interval: 1.08-3.38). No relationships were found between diabetic retinopathy or diabetic nephropathy and ED. Diabetic neuropathy is positively associated with severe erectile dysfunction among Japanese type 2 diabetes mellitus patients aged <65 years.

Depressive symptoms and prevalence of erectile dysfunction in Japanese patients with type 2 diabetes mellitus: the Dogo Study.

In several studies of patients with type 2 diabetes mellitus, a positive association between depressive symptoms and erectile dysfunction (ED) has been reported. No evidence exists, however, regarding the association between depressive symptoms and ED among Japanese patients with type 2 diabetes mellitus. Thus, we examined this issue among Japanese patients with type 2 diabetes mellitus. Study subjects were 469 male Japanese patients with type 2 diabetes mellitus, aged 19 years or over. ED, moderate to severe ED and severe ED were defined as present when a subject had a Sexual Health Inventory for Men score <22, <12 and <8, respectively. Depressive symptoms were defined as present when a subject had a Self-Rating Depression Scale (SDS) score >49. Adjustment was made for age, body mass index, waist, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, coronary artery disease, stroke, glycated hemoglobin and diabetic neuropathy. The prevalence values of depressive symptoms, moderate to severe ED and severe ED were 15.1%, 64.2% and 51.0%, respectively. Depressive symptoms were independently positively associated with moderate to severe ED and severe ED (adjusted odds ratios were 2.23 (95% confidence interval (CI): 1.17-4.43) and 1.86 (95% CI: 1.04-3.41), respectively). In Japanese patients with type 2 diabetes mellitus, depressive symptoms may be associated with ED.

Stroke volume-directed administration of hydroxyethyl starch or Ringer's acetate in sitting position during craniotomy.

BACKGROUND: To determine the volumes required for stable haemodynamics and possible effects on the coagulation, we studied stroke volume (SV)-directed administration of hydroxyethyl starch (HES 130 kDa/0.4) and Ringer's acetate (RAC) in neurosurgical patients operated on in a sitting position. METHODS: Thirty craniotomy patients were randomised to receive either HES or RAC. Before positioning, SV, measured by arterial pressure waveform analysis, was maximised by boluses of fluid until SV did not increase more than 10%. SV was maintained by repeated administration of fluid. RAC 3 ml/kg/h was infused in both groups during surgery. RESULTS: Comparable haemodynamics were achieved with the mean [standard deviation (SD)] cumulative doses of HES or RAC 271 (47) or 264 (50) ml (P = 0.699) before the sitting position. Mean (SD) doses of HES or RAC at 30 min after the positioning were 343 (94) or 450 (156) ml (P = 0.036), and at the end of surgery 464 (284) or 707 (425) ml, respectively (P = 0.087). The intraoperative fluid balance was more positive in the RAC than in the HES group [P = 0.044, 95% confidence interval (CI) -978 to -14]. Cardiac and stroke volume indexes [CI and stroke volume index (SVI)] increased in the HES group (P < 0.05) but not in the RAC group [non significant (N.S.)]. Neither coagulation profile nor blood loss differed between the groups. CONCLUSION: Fluid filling with HES boluses resulted in a positive response in CI and SVI during the sitting position. The 34% smaller volume of HES than crystalloid and less positive fluid balance in the HES group might be important in craniotomy patients with decreased brain compliance.

Effects of combined balanced colloid and crystalloid on rotational thromboelastometry in vitro.

Our objective was to investigate the in vitro effects of a totally balanced fluid concept on whole blood coagulation. Venous blood from 12 healthy volunteers was diluted by 20% and 40% with a combination of an equal amount of colloid (balanced or unbalanced 6% HES 130/0.4, or 4% gelatin) and crystalloid (balanced or unbalanced Ringer's acetate). Blood samples were analyzed with rotational thromboelastometry (ROTEM®). The initiation of coagulation was delayed in all dilutions except for the 20 vol% gelatin-dilution. In the extrinsic activation test, maximum clot firmness was decreased and clot formation time prolonged after 40 vol% hemodilution with a balanced Ringer's/unbalanced HES combination, more than in the corresponding gelatin hemodilution. In the fibrin-based test, after both 20- and 40 vol% hemodilution with unbalanced Ringer's/gelatin solution, maximum clot firmness was significantly stronger than in the Ringer's/HES-combinations. The combination of balanced colloid and crystalloid has similar coagulation effects in vitro as their respective combination of unbalanced solutions.

Adenosine and adenosine uptake inhibitors potentiate the neuromuscular blocking action of rocuronium mediated by adenosine A(1) receptors in isolated rat diaphragms.

BACKGROUND: Adenosine, which pre-junctionally modulates neuromuscular transmission, and adenosine uptake inhibitors, which increase extracellular adenosine, have been used clinically. We investigated the effects of adenosine, dipyridamole and midazolam on the neuromuscular blocking action of rocuronium. METHODS: Isometric twitch tensions of rat nerve-hemidiaphragm preparations elicited by indirect (phrenic nerve) supra-maximal stimulation at 0.1 Hz were evaluated (n=6 in all data). RESULTS: Pre-treatments with adenosine (0.1 and 1 microM) and CCPA (1 microM, adenosine A(1) receptor agonist), but not that with CGS21680 (0.5 microM, A(2) receptor agonist), shifted the rocuronium concentration-twitch tension curves to the left and decreased the rocuronium concentration for 50% twitch depression (IC(50)) compared with the control (P<0.01). The leftward shift induced by 1 microM adenosine was inhibited by pre-treatments with theophylline (50 microM, non-selective adenosine receptor antagonist) and DPCPX (0.2 microM, A(1) receptor antagonist) but not by that with DPMA (5 microM, A(2) receptor antagonist). Pre-treatments with dipyridamole and midazolam, adenosine uptake inhibitors, shifted the curve to the left and decreased IC(50) at supra-therapeutic concentrations (10 and 2.5 microM, respectively) but not at clinical concentrations (2 and 0.5 microM, respectively), and the leftward shifts were inhibited by pre-treatment with DPCPX (0.2 microM). CONCLUSION: The results indicate that adenosine potentiates the neuromuscular blocking action of rocuronium mediated by adenosine A(1) receptors and that supra-therapeutic concentrations of dipyridamole and midazolam also potentiate the action of rocuronium by increasing endogenous adenosine concentration.

Prediction of hepatic artery thrombosis by protocol Doppler ultrasonography in pediatric living donor liver transplantation.

Hepatic arterial thrombosis (HAT) after liver transplantation is a life-threatening event. Previous reports have suggested that the resistive index (RI) of the hepatic artery predicts HAT. Doppler ultrasonography (US) to measure RI, however, is not routinely performed. The subjects were 70 pediatric patients who underwent living donor liver transplantation (LDLT). Protocol Doppler US was performed once or twice a day for 2 weeks postoperatively and 692 records were examined. Changes in RI values were examined separately in patients with and without HAT complications. The incidence of HAT was 10% (seven of 70). HAT was diagnosed an average of 6.2 days after LDLT. In patients without HAT complications ( n = 63), average RI levels at 14 days after LDLT were 0.71 +/- 0.1 (records, n = 625). In patients with HAT complications, RI decreased gradually within 2 days before the onset of HAT. RI values of less than 0.6 predicted HAT within 2 days before onset, with 83% sensitivity and 85% specificity. RI during the first 2 weeks after LDLT is a sensitive predictor for HAT. Thrombectomy and reanastomosis should be considered when RI values are less than 0.6 in Doppler US.

T-cell large granular lymphocytic leukemia occurring after autologous peripheral blood stem cell transplantation.

A 61-year-old man with angioimmunoblastic lymphoma in first complete remission underwent autologous peripheral blood stem cell transplantation. At 1 month post transplant, asymptomatic large granular lymphocytosis developed. The surface marker profile of the cells was CD3+CD8+CD56-CD57+. The disease course was chronic and indolent. The patient remains in complete remission from angioimmunoblastic lymphoma more than 6 months post transplant with persistent large granular lymphocytosis (lymphocyte count, 5-15 x 10(9)/l). Although post transplantation T-cell lymphoproliferative disorders have mostly occurred in allogeneic transplantation recipients and presented as aggressive lymphomas/leukemias, we suggest that chronic indolent T-cell large granular lymphocytic leukemia can occur after autologous stem cell transplantation.

Multimodal inclusion complexes between barbiturates and 2-hydroxypropyl-beta-cyclodextrin in aqueous solution: isothermal titration microcalorimetry, (13)C NMR spectrometry, and molecular dynamics simulation.

Multiple types (structures) of inclusion complexes between barbiturates and 2-hydroxypropyl-beta-cyclodextrin (HPCD) were evaluated by isothermal titration microcalorimetry and (13)C NMR spectroscopy. The geometries of the inclusion complexes were suggested by molecular dynamics simulation. Barbituric acid (BA), barbital (B), amobarbital (AB), pentobarbital (PB), secobarbital (SB), cyclobarbital (CB), and phenobarbital (PHB) were used as barbiturates with different substituents on the barbituric acid ring and compared for inclusion types in aqueous solution. The association constants (K), stoichiometries, and thermodynamic parameters change in free energy (DeltaG) change in enthalpy (DeltaH), and change in entropy [DeltaS] for each type of complex were determined from the calorimetric data. The inclusion complexation was largely entropy driven because of hydrophobic interactions. The values of K increased in the order BA

Activation of mouse phosphodiesterase 3B gene promoter by adipocyte differentiation in 3T3-L1 cells.

Activation of phosphodiesterase (PDE) 3B reduces free fatty acid output from adipocytes. Induction of PDE3B gene expression by adipocyte differentiation could improve insulin resistance. To examine whether the PDE3B promoter is activated by this differentiation, the 5' flanking sequence of the mouse PDE3B gene was isolated. The transcription initiation site was determined to be located 195 bp upstream of the translation start site. No putative binding site for peroxisome proliferator-activated receptor gamma was found within 2 kb upstream of the transcription initiation site. This region had promoter activity, which was further activated on adipocyte differentiation in 3T3-L1 cells.

Anti-transforming growth factor-beta1 antibody transiently enhances DNA synthesis during liver regeneration after partial hepatectomy in rats.

The regulation of liver regeneration after partial hepatectomy (PHx) is complex and involves many different cytokines. We investigated the role of one of these, transforming growth factor-beta1 (TGF-beta1), an inhibitor of liver regeneration, in a Wistar male rat model, in which anti-TGF-beta1 antibody was injected immediately or 24 h after 70% PHx. Livers from treated animals contained an increased number of cells in S phase, according to 5-bromo-2'-deoxyuridine (BrdU) labeling 36 h after PHx. Antibody administration 24 h after PHx resulted in the highest peak of proliferation; moreover, peak MIB-5 labeling was also observed at that time. However, neither residual liver-weight-to-body-weight ratios nor regeneration rates differed significantly between any of the animals. Therefore, we also measured levels of serum TGF-beta1 and hepatocyte growth factor (HGF; an activator). With antibody administration at 0 or 24 h, TGF-beta1 levels were diminished at 24 or 36 h as compared with levels in control rats, but then rebounded, reaching a delayed peak at 48 or 72 h after PHx, respectively. Interestingly, there were also similar trends in HGF levels. These results indicate that TGF-beta1 may inhibit the G1 checkpoint, and serum TGF-beta1 concentration may influence HGF to regulate liver regeneration and to maintain homeostasis of proliferation after PHx.

Ab initio molecular orbital study of reactivity of active alkyl groups. IV. Nitrosation of acyclic carbonyl compound with methyl nitrite via "open-chain" transition state.

The mechanism of the nitrosation of enolate anion of acetone [CH3COCH2]- (1) with methyl nitrite CH3ONO (2) via an "open-chain" transition state without Na+ in the C-N bond formation process was studied by the ab initio MO method. The complex [CH3COCH2NO(OCH3)]- (C-II) was first formed from the adduct (C-I) of 1 and 2 through the transition state (TSI). Finally, E-1-hydroxyimino-2-oxo-propane CH3COCH=NOH (3E), together with Z-form (3Z), was obtained by way of the elimination process. It has become apparent that 3E is formed when C-II-A is produced in the C-N bond formation process.

Identification of novel C253Y missense and Y864X nonsense mutations in the insulin receptor gene in type A insulin-resistant patients.

Mutations in the insulin receptor gene have been reported in cases of type A insulin resistance. We report herein two cases of type A insulin resistance, which involve some novel mutations. Case 1 is a heterozygote of the C253Y missense mutation and case 2 is a heterozygote of the Y864X nonsense mutation. In the C253Y missense mutation in exon 3, a cysteine residue is replaced with tyrosine in the cysteine-rich domain of the alpha subunit. The Y864X in exon 13 results in a truncated receptor, which is devoid of most of the beta subunit. This mutant receptor could not be expressed on a cell membrane since the transmembrane domain is missing. Other significant mutations were not found for the entire coding regions and splice/donor sites.

Effect of methylprednisolone on the kinetics of cytokines and liver function of regenerating liver in rats.

The participation of cytokines in the early stage mechanism of hepatocyte proliferation has already attracted attention. We investigated the effect of methylprednisolone (MDS), which inhibits the inflammatory response, given before and after a 70% partial hepatectomy in rats on the kinetics of tumor necrosis factor-alpha and Interleukin-6, liver cell function and the rate of liver regeneration. Serum Interleukin-6 levels of the MDS groups were significantly lower than those of the control group. Serum alanine aminotransferase, aspartate aminotransferase and hyaluronic acid levels were also significantly decreased, however, the serum albumin level showed high values in the MDS groups. In the MDS groups, MIB-5 labeling indices, a novel antibody reactive with the equivalent Ki-67 protein, which detects immunohistochemically all active parts of the cell cycle in the rat liver, were more pronounced than in the control group at an earlier time. However, in regard to 5-bromo-2-deoxyuridine (BrdU), there were no significant differences among the three groups. There were no differences in residual liver weight/body weight between the three groups after 336 h. In our study, MDS administration before or after a 70% partial hepatectomy decreased serum Interleukin-6 levels, and inhibited hepatic dysfunction. Therefore, we considered that beneficial effects of physiological doses of MDS in the peri-operative period should be confirmed in humans.

Celite-activated viscometer Sonoclot can measure the suppressive effect of tranexamic acid on hyperfibrinolysis in cardiac surgery.

PURPOSE: To investigate the usefulness of the celite-activated viscometer Sonoclot for monitoring fibrinolytic status in cardiac surgery, we demonstrated the effectiveness of high doses of tranexamic acid, an antifibrinolytic agent, in reducing postoperative bleeding. METHODS: Thirty-two American Society of Anesthesiologists (ASA) physical status III patients who required cardiac surgery with cardiopulmonary bypass (CPB) were studied. Anesthesia was induced by a high dose of fentanyl and midazolam with oxygen and was maintained by the intermittent administration of these agents. Patients were divided into two groups: the control group (n = 15) and patients receiving tranexamic acid (TA; n = 17). The TA group received a high dose (50 mg/kg) of TA twice, once before and once after CPB. The percentage diminishing rate of the Sonoclot tracing 15 min after maximum clot signal (DR(15)) and the amount of postoperative bleeding were measured. RESULTS: After CPB, DR(15) in the control group (mean 28.3%) increased significantly by 45%, and the DR(15) in the TA group (16.1%) was significantly lower than that in the control group. The amount of postoperative bleeding in the TA group (546 ml) was significantly less, by 34%, than that in the control group (829 ml). CONCLUSION: Prophylactic administration of high-dose TA in cardiac surgery reduces postoperative bleeding, and this effect is consistent with changes in the diminishing rate using Sonoclot. The celite-activated viscometer Sonoclot is recommended for use in cardiac surgery for rapid assessment of fibrinolytic status.

Effects of counter cations of base catalysts on nitrosation mechanisms.

Reaction of 2-butanone (1) with tert-butyl nitrite (tert-BuONO) was performed using base catalysts (RO-M+: R=CH3, C2H5; M+=Li+, Na+, K+) in alcohols (CH3OH or C2H5OH). In this report, the effects of M+ of RO-M+ on the nitrosation mechanisms were investigated. The yield of E-hydroxyimino compound (5E) increases much better in the reaction using Na+ or K+ as M+ compared with that using Li+. It is also observed that the yield of 5E increases by addition of crown ether as a cation-capturing agent. The experimental results suggested that under the conditions lowering the effects of M+ of RO-M+ on the nitrosation mechanisms, because the reactivity of naked enolate of I increases and the reaction in the C-N bond formation process tends to proceed via open-chain transition state without M+, the yield of 5E tends to increase.

The utility of three-dimensional computed tomography in unanticipated difficult endotracheal intubation.

IMPLICATIONS: We experienced a case of unanticipated difficult intubation with direct laryngoscopy because of narrowing of the retropharyngeal air space and laryngeal vestibulum. It is suggested that three-dimensional computed tomography is useful for evaluating both the abnormality of an airway and its relationship to surrounding tissue.

A complete deficiency of coagulation factor XIII A-subunit due to a novel compound heterozygote of Ser 413 Leu missense and an nt 389 (ins G) frameshift mutation.

Coagulation factor XIII consists of two A- and two B-subunits, and either gene mutation can cause a complete deficiency. In a newborn patient with persistent bleeding from the umbilical cord stump, the plasma A-subunit protein was not detectable. Direct PCR sequencing revealed an nt 389 (ins G) frameshift mutation in exon 4 resulting in a new stop codon and a Ser 413 Leu missense mutation in exon 10 in either allele. His mother and father were heterozygous for the nt 389 (ins G) and the Ser 413 Leu, respectively, with about 50% reduction of the plasma A-subunit proteins. In all family members examined only those with either mutation showed the reduced subunit A protein levels. Thus, this complete deficiency of factor XIII was due to a novel compound heterozygous mutation in the A-subunit gene.

Immediate increase of portal pressure, reflecting sinusoidal shear stress, induced liver regeneration after partial hepatectomy.

The mechanisms whereby hepatocytes in the normal liver can be primed for replication following partial hepatectomy (PHx) are poorly understood. To determine whether "shear stress," which is induced by acute portal hypertension after PHx, is involved in liver regeneration, we studied liver regeneration in rats with splenic transposition (SPT) in which we can minimize the postoperative elevation of portal pressure. Rats underwent 70% PHx following splenic transposition or sham surgery and were killed at various time points to measure portal pressure and other factors. In the control groups, the portal pressure was significantly increased immediately after surgery, peaking at 48 h, and returning to near the preoperative levels by 168 h after PHx. In the SPT group, although portal pressure increased immediately, it decreased to the control levels 6 h after PHx and thereafter repeatedly increased. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels peaked at 24 and 6 h after PHx, respectively. Proliferative cell analysis was done using MIB-5 antibody, and there were no significant differences between the two groups. Furthermore, liver weight was restored in the same way in both groups. Taken together, the results suggest that an immediate increase in portal pressure is necessary for the initiation of liver regeneration.

[A feature of hematological findings in myelodysplastic syndromes].

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis in one or more hematopoietic lines with abnormal morphology and peripheral blood cytopenia. Primary MDS are more common in elderly patients and rare in children and young adults. The diagnosis of MDS in patients with unexplained cytopenias requires careful morphologic evaluation of both the peripheral blood and bone marrow cells. To examine which abnormalities detected by routine examination suggest MDS, we analyzed the hematological findings of peripheral blood in seventy-six cases of MDS. Anemia (> 60%), leukopenia (> 40%), thrombocytopenia (> 70%) as well as blast (> 40%) were often found. The prevalence of MDS was relatively high in patients with morphological abnormalities such as elliptocyte, dacryocyte, erythroblast, pseudo-Pelger-Huet anomaly, decreased secondary granules and giant platelets. Careful attention should be paid to these findings especially elderly patients, since these may provide clues to the diagnosis of MDS.