Elevation of serum high molecular weight adiponectin in patients with Type 2 diabetes and orthostatic hypotension: association with arterial stiffness and hypercoagulability.

AIM: Orthostatic hypotension is a hallmark of diabetic autonomic neuropathy and is associated with increased mortality. The serum level of adiponectin is elevated in patients with heart failure or renal failure. In the present study, we measured serum levels of total and high molecular weight adiponectin in patients with Type 2 diabetes and orthostatic hypotension. We also investigated the relationship between the presence of orthostatic hypotension and various clinical variables in patients with Type 2 diabetes. METHODS: We studied 105 patients with Type 2 diabetes. Orthostatic hypotension was defined as a decrease of 20 mmHg or more in systolic blood pressure and/or 10 mmHg in diastolic blood pressure when blood pressure was measured for 3 min while standing. The brachial-ankle pulse-wave velocity was also measured as an index of arterial stiffness. RESULTS: Orthostatic hypotension was found in 30 patients with diabetes (28.6%). The haematocrit and estimated glomerular filtration rate were significantly lower in patients with orthostatic hypotension than in those without it. Brachial-ankle pulse-wave velocity and serum total and high molecular weight adiponectin were significantly higher in patients with orthostatic hypotension than in those without. Furthermore, the high molecular weight/total adiponectin ratio was higher in patients with orthostatic hypotension than in those without and hypertension was more common in patients with orthostatic hypotension. Plasma prothrombin F1 + 2, a coagulation maker, was higher in patients with orthostatic hypotension than in those without, while there were no differences of fibrinolytic markers between the two groups. Multivariate analysis showed that HDL cholesterol, haematocrit, F1 + 2, brachial-ankle pulse-wave velocity and a decline of systolic blood pressure on standing were independent determinants of high molecular weight adiponectin. CONCLUSIONS: Patients with Type 2 diabetes and orthostatic hypotension had an elevated serum level of high molecular weight adiponectin, which was associated with the simultaneous presence of renal dysfunction, anaemia, arterial stiffness and hypercoagulability.

The recovery of cognitive function after general anesthesia in elderly patients: a comparison of desflurane and sevoflurane.

UNLABELLED: We evaluated the cognitive recovery profiles in elderly patients after general anesthesia with desflurane or sevoflurane. After IRB approval, 70 ASA physical status I-III consenting elderly patients (> or =65 yr old) undergoing total knee or hip replacement procedures were randomly assigned to one of two general anesthetic groups. Propofol and fentanyl were administered for induction of anesthesia, followed by either desflurane 2%-4% or sevoflurane 1%-1.5% with nitrous oxide 65% in oxygen. The desflurane (2.5 +/- 0.6 MAC. h) and sevoflurane (2.7 +/- 0.5 MAC. h) concentrations were adjusted to maintain comparable depths of hypnosis using the electroencephalogram bispectral index monitor. The Mini-Mental State (MMS) test was used to assess cognitive function preoperatively and postoperatively at 1, 3, 6, and 24-h intervals. The use of desflurane was associated with a more rapid emergence from anesthesia (6.3 +/- 2.4 min versus 8.0 +/- 2.8 min) and a shorter length of stay in the postanesthesia care unit (213 +/- 66 min versus 241 +/- 87 min). However, there were no significant differences between the Desflurane and the Sevoflurane groups when the MMS scores were compared preoperatively, and postoperatively at 1, 3, 6, and 24 h. Compared with the preoperative (baseline) MMS scores, the values were significantly decreased at 1 h postoperatively (27.8 +/- 1.7 versus 29.5 +/- 0.5 in the Desflurane group, and 27.4 +/- 1.7 versus 29.2 +/- 1.0 in the Sevoflurane group, respectively). However, the MMS scores returned to preoperative baseline levels within 6 h after surgery. At 1 h and 3 h after surgery, 51% and 11% (versus 57% and 9%) of patients in the Desflurane (versus Sevoflurane) Group experienced cognitive impairment. In conclusion, desflurane is associated with a faster early recovery than sevoflurane after general anesthesia in elderly patients. However, recovery of cognitive function was similar after desflurane and sevoflurane-based anesthesia. IMPLICATIONS: Desflurane was associated with a faster early recovery than sevoflurane after general anesthesia in elderly patients. However, recovery of cognitive function was similar with both volatile anesthetics.

The effect of timing of dolasetron administration on its efficacy as a prophylactic antiemetic in the ambulatory setting.

UNLABELLED: Dolasetron (12.5 mg IV) is effective in both preventing and treating postoperative nausea and vomiting (PONV) after ambulatory surgery. However, the optimal timing of dolasetron administration and its effect on the patient's quality of life after discharge have not been established. One-hundred-five healthy, consenting women undergoing gynecologic laparoscopic procedures with a standardized general anesthetic technique were enrolled in this randomized, double-blinded study. Group 1 received dolasetron 12.5 mg IV 10-15 min before the induction of anesthesia; Group 2 received dolasetron 12.5 mg IV at the end of the laparoscopy (79 +/- 48 min later than Group 1); and Group 3 received dolasetron 12.5 mg IV at the end of anesthesia (93 +/- 52 min later than Group 1). The incidence of PONV, complete responses (defined as no emetic episodes and no rescue medication within the 24-h period after anesthesia), recovery profiles, and patient satisfaction were recorded. In the postanesthesia care unit and during the 24-h follow-up period, the incidence of nausea and vomiting, as well as the need for rescue antiemetics, did not differ significantly among the three groups. The percentages of patients with complete responses to the study drug within the first postoperative 24 h were also similar in all three groups (55%, 59%, and 52% for Groups 1, 2, and 3, respectively). The early and intermediate recovery profiles, including resumption of a normal diet and patient satisfaction with the control of PONV, were not different among the three study groups. Dolasetron 12.5 mg IV administered before the induction of anesthesia is as effective as dolasetron given at the end of laparoscopy or at the end of anesthesia in preventing PONV after outpatient laparoscopy. IMPLICATIONS: The timing of dolasetron administration appears to have little effect on its efficacy when administered as a prophylactic antiemetic in the ambulatory setting.

Fast-track office-based anesthesia: a comparison of propofol versus desflurane with antiemetic prophylaxis in spontaneously breathing patients.

IMPLICATIONS: Compared to propofol, maintenance of anesthesia with desflurane provided significantly better intraoperative conditions during office-based surgery. In addition, desflurane with routine antiemetic prophylaxis was associated with a faster early recovery and similar incidence of postoperative side effects.

Use of propofol for office-based anesthesia: effect of nitrous oxide on recovery profile.

STUDY OBJECTIVE: To evaluate the effect of nitrous oxide (N2O) on the recovery profile and the incidence of postoperative nausea and vomiting (PONV) after office-based surgery performed under propofol anesthesia. DESIGN: Prospective, randomized, single-blind study. SETTING: Office-based surgical center. PATIENTS: 69 ASA physical status I, II, and III healthy, consenting outpatients undergoing superficial surgical procedures lasting 15 to 45 minutes. INTERVENTIONS: After a standard propofol induction (1.5 mg.kg-1 i.v.), anesthesia was initially maintained with propofol, 100 micrograms.kg-1.min-1 i.v., in combination with either air or N2O 65% in oxygen. The propofol infusion rate was subsequently varied to maintain an adequate depth of anesthesia. All patients received local anesthetic infiltration prior to the surgical incision, as well as during the operation. No prophylactic antiemetics were administered. MEASUREMENTS AND MAIN RESULTS: Recovery times and the incidences of PONV were recorded during the first 24 hours after surgery. Early and late recovery variables were similar in the two treatment groups; however, 65% N2O produced a 19% decrease in the propofol maintenance dosage requirement. One patient (3%) experienced nausea prior to discharge in the propofol-N2O group, and two patients (6%) experienced nausea at home in the propofol alone group. None of the patients vomited or received antiemetic medication during the 24 hours postdischarge period. Ninety-seven percent of patients receiving propofol alone and all of the patients in the propofol-N2O group were "very satisfied" with their anesthetic experience. CONCLUSIONS: In outpatients undergoing office-based surgical procedures with propofol anesthesia, administration of 65% N2O decreased the anesthetic requirement without increasing PONV. Therefore, use of a propofol-N2O combination may be a cost-effective alternative to propofol alone for office-based anesthesia.

Recovery profile, costs, and patient satisfaction with propofol and sevoflurane for fast-track office-based anesthesia.

BACKGROUND: Office-based surgery is becoming increasingly popular because of its cost-saving potential Both propofol and sevoflurane are commonly used in the ambulatory setting because of their favorable recovery profiles. This clinical investigation was designed to compare the clinical effects, recovery characteristics, and cost-effectiveness of propofol and sevoflurane when used alone or in combination for office-based anesthesia. METHODS: One hundred four outpatients undergoing superficial surgical procedures at an office-based surgical center were randomly assigned to one of three general anesthetic groups. In groups I and II, propofol 2 mg/kg was administered for induction followed by propofol 75-150 microg x kg(-1) x min(-1) (group I) or sevoflurane 1-2% (group II) with N2O 67% in oxygen for maintenance of anesthesia In group m, anesthesia was induced and maintained with sevoflurane in combination with N2O 67% in oxygen. Local anesthetics were injected at the incision site before skin incision and during the surgical procedure. The recovery profiles, costs of drugs, and resources used, as well as patient satisfaction, were compared among the three treatment groups. RESULTS: Although early recovery variables (e.g., eye opening, response to commands, and sitting up) were similar in all three groups, the times to standing up and to be "home ready" were significantly prolonged when sevoflurane-N2O was used for both induction and maintenance of anesthesia. The time to tolerating fluids, recovery room stay, and discharge times were significantly decreased when propofol was used for both induction and maintenance of anesthesia. Similarly, the incidence of postoperative nausea and vomiting and the need for rescue antiemetics were also significantly reduced after propofol anesthesia. Finally, the total costs and patient satisfaction were more favorable when propofol was used for induction and maintenance of office-based anesthesia CONCLUSION: Compared with sevoflurane-N2O, use of propofol-N2O for office-based anesthesia was associated with an improved recovery profile, greater patient satisfaction, and lower costs. There were significantly more patients who were dissatisfied with the sevoflurane anesthetic technique.

The effect of location of transcutaneous electrical nerve stimulation on postoperative opioid analgesic requirement: acupoint versus nonacupoint stimulation.

UNLABELLED: Transcutaneous electrical nerve stimulation (TENS) has been used as a complementary (supplemental) therapy to opioid analgesics for pain relief after surgery. Simultaneous stimulation at a classical Chinese acupoint site and periincisional dermatomes significantly decreases the postoperative analgesic requirement. This sham-controlled study was designed to assess the relative effectiveness of acupoint versus nonacupoint stimulation on the postoperative hydromorphone (HM) requirement, the incidence of opioid-related side effects, and the overall recovery profile. One hundred women undergoing total abdominal hysterectomy or myomectomy procedures with a standardized general anesthesia were randomly assigned to one of four postoperative analgesic treatment regimens (n = 25 each): Group I = sham-TENS (no electrical current) at the Zusanli (ST36) acupoints, Group II = nonacupoint-TENS at the shoulders, Group III = dermatomal-TENS at the level of the surgical incision, and Group IV = acupoint-TENS at the Zusanli acupoints. The frequency of TENS was set in the standard dense-and-disperse mode of 2/100 Hz. The intensity of stimulation was set at 0 mA for patients in Group I and at 9-12 mA for patients in Groups II, III, and IV. A patient-controlled analgesia (PCA) device programmed to deliver bolus doses of HM 0.2-0.4 mg IV on demand with a minimal lockout interval of 10 min was used to quantify the postoperative opioid analgesic requirement. Standard 100-mm visual analog scales were used to assess pain, as well as sedation, fatigue, and nausea, at specific intervals after surgery. The numbers of PCA demands and delivered bolus doses, requirements for supplemental medication, and any opioid-related side effects were recorded. In the first 24 h postoperatively, the opioid requirements in Groups III and IV were decreased by 37% and 39%, respectively, compared with the control (sham) group and 35% and 38%, respectively, compared with Group II. The duration of PCA usage and the incidences of nausea and dizziness were also significantly decreased in Groups III and IV compared with Groups I and II. We conclude that periincisional dermatomal and Zusanli acupoint stimulation were equally effective in decreasing the postoperative opioid analgesic requirement and in reducing opioid-related side effects. Both of these positions were more effective than the nonacupoint (shoulder) location. IMPLICATIONS: The location of the stimulating electrodes seems to be an important determinant of the efficacy of transcutaneous electrical nerve stimulation in decreasing the need for opioid analgesics in the postoperative period. This study demonstrates that transcutaneous electrical nerve stimulation applied at the dermatomal level of the skin incision is as effective as Zusanli acupoint stimulation, and both were more effective than stimulation at a nonacupoint (shoulder) location.

Effect of the intensity of transcutaneous acupoint electrical stimulation on the postoperative analgesic requirement.

Given the inherent side effects associated with both opioid and nonopioid analgesic drugs, a nonpharmacologic therapy that could decrease the need for analgesic medication would be valuable. We designed a sham-controlled study to assess the effect of the intensity of transcutaneous acupoint electrical stimulation (TAES) on postoperative patient-controlled analgesia (PCA) requirement for hydromorphone (HM), the incidence of opioid-related side effects, and the recovery profile after lower abdominal surgery. One hundred one healthy consenting women undergoing lower abdominal procedures with a standardized general anesthetic technique were randomly assigned to one of four postoperative analgesic treatment regimens: Group I (n = 26) PCA only; Group II (n = 25), PCA + sham-TAES (no electrical stimulation); Group III (n = 25), PCA + low-TAES (4-5 mA of electrical stimulation); Group IV (n = 25), PCA + high-TAES (9-12 mA of electrical stimulation). The PCA device was programmed to deliver HM, 0.2-0.4 mg intravenously boluses "on demand," with a minimum lockout interval of 10 min. The TAES skin electrodes were placed at the Hegu acupoint on the nondominant hand and on both sides of the surgical incision. The TAES frequency was set in the dense-and-disperse mode, alternating at 2 Hz and 100 Hz every 3 s, with stimulation of the hand and incision alternated every 6 s. The patients in Groups II-IV were instructed to use TAES every 2 h for 30 min while awake. After discontinuation of PCA, oral pain medications were administered on demand. The postoperative PCA-HM requirement, pain scores, opioid-related side effects, and requirements for antiemetic and antipruritic medication were recorded. High-TAES decreased the HM requirement by 65% and reduced the duration of PCA therapy, as well as the incidence of nausea, dizziness, and pruritus. Low-TAES produced a 34% decrease in the HM requirement compared with only 23% in the "sham" TAES group. We conclude that high-TAES produced a significant decrease in the PCA opioid requirement and opioid-related side effects after low intraabdominal surgery.

Antimetastatic effect of yeast mannan-bleomycin conjugate against mouse Lewis lung carcinoma.

A conjugate of bleomycin (BLM) and the mannan of bakers' yeast (Saccharomyces cerevisiae wild type strain) (WNM) was synthesized. The assay of its antimetastatic effect on Lewis lung carcinoma (3LL) implanted in C57BL/6 mice showed that this conjugate exhibited a higher antimetastatic effect and longer life-span elongation than those of free bleomycin and mannan with corresponding doses. This conjugate was also found to kill the 3LL cells in vitro. 14C-Labeled mannan-bleomycin conjugate was much more bound than 14C-labeled dextran-bleomycin conjugate to the 3LL. It was concluded that the anti-cancer mechanism of this conjugate, WNM-BLM possessed a specific binding effect to the tumor cells and exhibited a cytocidal effect on the 3LL target cells.

Potential usage of thermosensitive liposomes for macromolecule delivery.

Since transient swelling during phase transition of liposomes with hyper-osmotic internal aqueous phase may cause permeation of large molecules through the lipid bilayer, this type of liposomes can be useful for delivering macromolecules. In fact, thermosensitive liposomes containing an internal solution with osmotic pressure 2-fold higher than the physiologic level and sized through 200-nm pore, released encapsulated macromolecules such as dextran (M(r) 144,000) effectively when they were incubated at 40-42 degrees C. These liposomes were stable in the presence of serum compared to the liposomes with internal osmotic pressure more than 3-fold higher than the physiologic level.

[The tail suspension test: its theory and practical application].

The tail suspension test (TST) was originally proposed by Steru et al (1985) as a primary screening test of anti-depressant drugs. In this test, it is shown that tail suspension-induced immobility of mice is specifically antagonized by such drugs. More recently, the automated version of TST (ITEMATIC-TST) was developed by the same authors. In the present paper, we described our own device which utilized spring, contactless micro angle potentiometer, A/D converter and personal computer. Results obtained with this apparatus showed that repeated, not single, administration of tricyclic and atypical antidepressants could reverse the immobility of mice. Methamphetamine also activated the behavior, but other psychotropic drugs did not have positive results. Based on these findings, the usefulness and problems of our device were discussed as compared with the original TST.

[Serum monitoring of methotrexate (MTX) and 7-hydroxymethotrexate concentrations in patients treated with MTX using high-pressure liquid chromatography (HPLC) and comparison of serum MTX levels between HPLC method and fluorescence polarization immunoassay (FPIA)].

In order to measure simultaneously the serum levels of methotrexate (MTX) and its major metabolite, 7-hydroxymethotrexate (7-OH-MTX), in samples obtained from patients treated with MTX, we have investigated the reversed-phase high-pressure liquid chromatographic assay using ion-pairing reagents. The mobile phase consisted of 77.5% solution of 0.005M tetrabutylammonium and 22.5% acetonitrile. SEP-PAK C18 Cartridges were used for the precolumn. The detectable range of MTX and 7-OH-MTX were 0.02-0.03 and 1.0 mumol/l respectively. A significant positive correlation was observed (r = 0.983) between FPIA and HPLC methods. Serum MTX levels with FPIA were significantly (p less than 0.05) higher than those of HPLC method. The serum 7-OH-MTX levels at 24 hr and 48 hr were 4.857 +/- 1.383 (n = 10) and 1.835 +/- 0.286 (n = 6) mumol/l respectively with the dosage of 400 mg/m2. The serum 7-OH-MTX levels at 48 hr were 6.254 +/- 3.053 mumol/l (n = 5) with the dosage of 3,000 mg. The serum half lives of MTX and 7-OH-MTX were 8.05 +/- 1.03 (n = 4) and 14.8 +/- 1.35 (n = 6) hours respectively between 24 hr and 48 hr after administration. The T1/2 7-OH-MTX/MTX ratio was 1.8. Percent cross-reactivity of 7-OH-MTX with concentrations ranging from 1-10 mumol/l were 0.6-2.0% by FPIA. However, patients' serum levels of 7-OH-MTX were 15-85 times (n = 21) higher than those of MTX. MTX levels of containing both MTX and 7-OH-MTX (7-OH-MTX/MTX ratio was 50/1) were significantly higher than those of containing MTX alone by FPIA.

Antimetastatic and growth-inhibitory effects of N-acetylchitohexaose in mice bearing Lewis lung carcinoma.

N-Acetylchitohexaose, a water-soluble oligosaccharide was found to display a significant antimetastatic effect against Lewis lung carcinoma (LLC) transplanted into C57BL/6 mice, giving rise to a 40-50% inhibition ratio of pulmonary metastasis when administered intravenously (1 mg/kg) on day 6 after the tumor implantation (5 x 10(5) cells/mouse). It was also revealed that this hexaose had a significant growth-inhibitory effect against the local tumor of the same carcinoma (a 20-30% inhibition ratio), showing an enhancing effect on concomitant immunity in local tumor-resected mice. This oligosaccharide was also shown to enhance the tumoricidal effect of splenic T lymphocytes against LLC and P-815 mastocytoma cells and to increase the natural killer activity of splenic T lymphocytes, assayed with YAC-1 cells as the target.

In vivo quantification of receptor-mediated uptake of asialoglycoproteins by rat liver.

The in vivo kinetics of hepatic clearance of 125I-asialo-orosomucoid and 125I-asialofetuin was determined with a portal vein injection technique in barbiturate-anesthetized rats. Nonlinear regression analyses of saturation data gave the following parameters for asialo-orosomucoid, Km = 0.26 +/- 0.06 mg/ml, Vmax = 320 +/- 70 micrograms/min/g, and for asialofetuin, Km = 0.32 +/- 0.07 mg/ml, Vmax = 240 +/- 40 micrograms/min/g. Unlabeled asialofetuin inhibited the clearance of 125I-asialo-orosomucoid with a Ki = 0.25 +/- 0.04 mg/ml. Based on a model assuming that in vivo receptor concentration much greater than receptor KD, then the maximal binding capacity of the external surface of liver cells in vivo for asialo-orosomucoid is 2Km or 520 micrograms/ml or 52 micrograms/g of liver, assuming the liver interstitial space is 0.1 ml/g. Our estimate of in vivo binding capacity approximates in vitro estimates of total hepatic binding capacity, but is 10-fold greater than in vitro estimates of binding capacity on the external surface of liver cells. These results suggest the large majority of asialoglycoprotein receptors are located on the external surface of liver cells. The saturability of 125I-asialo-orosomucoid clearance was also demonstrated with a portal vein double bolus technique, wherein the portal injection of 20-1000 micrograms of unlabeled asialo-orosomucoid was followed 30 s later by the portal injection of tracer. Maximal inhibition of uptake was obtained with a portal vein injection of greater than or equal to 500 micrograms of asialo-orosomucoid. The specific extraction of the 125I-asialo-orosomucoid, which was near zero shortly after a 400-micrograms loading dose, gradually increased toward normal levels with a t1/2 of 21 min. This t1/2 may represent the in vivo rate of receptor recycling, since the gradual increase in unoccupied receptor sites is consistent with the model of receptor binding, internalization, and recycling.