While acetylcholinesterase inhibitors, such as donepezil, galantamine, and rivastig-mine, are beneficial in treating behavioral symptoms of patients with Alzheimer's disease (AD), their dose-limiting ...effects include gastrointestinal disturbances, such as nausea, vomiting, and diarrhea. We aimed to predict the occurrence of these gastrointestinal disturbances with rivastigmine therapy for optimal drug choice and improved compliance.
Thirty patients with mild-to-moderate AD (scores 10-22 on the MiniMental State Examination) were administered a rivastigmine 18 mg patch with domperidone 30 mg (RWD) and without domperidone (RWOD; n = 15 each) for 20 weeks. Gastrointestinal disturbances were evaluated using a frequency scale for symptoms of gastroesophageal reflux disease (FSSG), Bristol stool form scale, laboratory data (hemoglobin, albumin, total cholesterol), body weight, and amount of food intake.
After 12 weeks, FSSG scores were higher in the RWOD group compared to baseline scores; however, no significant differences were noted between the RWD and RWOD groups. We then subdivided each group based on high and low baseline scores; the RWOD high-score (≥4) subgroup showed increased FSSG after 12 weeks compared with the baseline score. In both RWD and RWOD groups, the low-score (≤3) subgroups showed no changes during the dose-escalation phase.
For AD patients with higher FSSG scores at baseline, domperidone was effective in preventing rivastigmine-related gastrointestinal disturbances.
Antipsychotics can induce hypothermia, but intraoperative temperature regulation in schizophrenic patients taking antipsychotics remains unclear. We investigated intraoperative temperature regulation ...and postoperative shivering in chronic schizophrenic patients receiving antipsychotics. We studied 30 schizophrenic patients and 30 control patients who underwent orthopedic surgery. Tympanic membrane temperatures (35.7 degrees C +/- 0.5 degrees C, 35.6 degrees C +/- 0.5 degrees C, 35.6 degrees C +/- 0.4 degrees C, 35.5 degrees C +/- 0.4 degrees C, 35.4 degrees C +/- 0.5 degrees C, and 35.4 degrees C +/- 0.3 degrees C) 15, 30, 45, 60, 75, and 90 min, respectively, after induction in schizophrenic patients were significantly (P < 0.001) lower than those (36.5 degrees C +/- 0.5 degrees C, 36.4 degrees C +/- 0.5 degrees C, 36.3 degrees C +/- 0.4 degrees C, 36.2 degrees C +/- 0.5 degrees C, 36.2 degrees C +/- 0.4 degrees C, and 36.1 degrees C +/- 0.4 degrees C) in control patients. Mean skin temperatures (31.1 degrees C +/- 0.4 degrees C P = 0.008, 31.1 degrees C +/- 0.3 degrees C P = 0.007, and 31.1 degrees C +/- 0.2 degrees C P = 0.006) 60, 75, and 90 min, respectively, after induction in schizophrenic patients were significantly lower than those (31.5 degrees C +/- 0.3 degrees C, 31.5 degrees C +/- 0.3 degrees C, and 31.5 degrees C +/- 0.3 degrees C) in control patients. Four of 30 schizophrenic patients and 7 of 30 control patients developed postanesthesia shivering. There were no significant differences within 1 h after tracheal extubation in tympanic membrane temperatures between patients who shivered and those who did not shiver. In conclusion, chronic schizophrenic patients were more hypothermic during anesthesia. The incidence of postanesthesia shivering was not significantly increased.
Antipsychotics inhibit autonomic thermoregulation. This is caused by decreased heat production, increased heat loss, and impaired central action at the hypothalamus. Thus, schizophrenic patients receiving antipsychotics may have impaired intraoperative temperature regulation.
We investigated the change of plasma cytokines concentrations in elderly patients during lower abdominal surgery. Plasma interleukin (IL-)6 concentrations (68.0±15.4 and 36.1±20.7pg/ml) in elderly ...patients at 24h and at 3 days after surgery were significantly higher than those (35.1±21.5 and 18.6±10.6pg/ml) of young adults. Plasma IL-6 concentrations (92.3± 31.9pg/ml) in elderly patients anesthetized with propofol and fentanyl were significantly higher at the end of the operation than that (57.9±36.7pg/ml) of elderly patients anesthetized with sevoflurane and fentanyl. In conclusion, elderly patients have an increased and delayed IL-6 response to surgical trauma compared with young adults. Plasma IL-6 production after surgical trauma in elderly patients with total intravenous anesthesia with propofol was significantly higher than that in elderly patients with sevoflurane anesthesia.
Little is known about the interaction of noradrenaline with volatile anesthetics in inhibitory synaptic transmission. The purpose of the present study was to investigate the interactions of ...noradrenaline and sevoflurane on inhibitory synaptic transmission mediated by GABA(A) receptors in the rat hippocampus. Pharmacologically isolated GABA(A) receptor-mediated IPSCs were recorded with whole-cell patch-clamp techniques in pyramidal neurons of the CA1 region of rat hippocampal slices. The actions of noradrenaline, noradrenaline analog, sevoflurane, and the interactions of these agents on the frequency and kinetics of spontaneous GABA(A) receptor-mediated IPSCs were studied. Noradrenaline (10 μM) caused an increase in the frequency of action potential-dependent sIPSCs. These effects were completely reversed by the addition of tetrodotoxin (1 μM), suggesting that noradrenaline produces the discharge of GABAergic interneurons innervating on pyramidal cells via adrenoceptors. Although sevoflurane (0.40 mM, 20 min) slightly depressed the amplitude of sIPSCs, sevoflurane significantly prolonged the decay time constant to 451.1 ± 89.0% of control (
n = 9,
P < 0.001) without affecting the rise time. In addition, sevoflurane increased the frequency of sIPSCs up to 3-fold. However, pretreatment of cadmium, multiple Ca channel blocker, abolished sevoflurane effects on the frequency whereas the effects on the decay were still observed. Application of both noradrenaline and sevoflurane produced a significant increase of the IPSC frequency than that of noradrenaline alone or sevoflurane alone with prolonged decays. These results provide evidence that both agents have additive effects on GABAergic synaptic transmission at the central nervous system via different mechanisms.
Microbial transglutaminase (MTG), an enzyme that works in posttranslational modification of proteins, has been applied to in vitro preparation of a bi-functional fusion protein from separately ...obtained recombinant proteins. A quite simple strategy in which a specific peptidyl linker recognizable by MTG is fused to the N-terminus of proteins of interest has been verified in the preparation of a bi-functional fusion protein using an antibody variable domain (single chain Fv of anti-hen-egg white lysozyme antibody, scFv) and a fluorescent protein (enhanced yellow fluorescent protein, EYFP). The resultant peptidyl linker-fused proteins were readily cross-linked by MTG to only give the heterodimer (i.e. scFv-EYFP fusion protein), suggesting that the reaction proceeded in highly specific manner. As the fusion protein exhibited sufficient bi-functionality in fluorescence immunoassay (FIA), this work shows for the first time a successful enzymatic preparation of a bi-functional fusion protein through recombinantly incorporated specific peptidyl linkers into target proteins.
We investigated temperature regulation during anesthesia and postoperative shivering in chronically depressed patients given antidepressant drugs. We studied 35 depressed patients and 35 control ...patients who underwent orthopedic surgery. Tympanic membrane temperatures 60, 75, and 90 min after induction in the depression group were significantly (P < 0.05) higher than those of the control group. There were no significant differences in mean skin temperature between the depression and the control groups. Eight of 35 patients in the depression group and 2 of 35 patients in the control group developed postanesthetic shivering. The incidence of shivering in the depression group was significantly more frequent than that in the control group (P = 0.04). The tympanic membrane temperature of the patients treated with clomipramine tended to be higher than that of the patients treated with maprotiline. In conclusion, intraoperative core hypothermia in chronically depressed patients was decreased. However, the incidence of shivering in depressed patients was significantly more frequent.
Thermoregulation in chronically depressed patients is often altered. The alteration of body temperature is affected by depression itself and by antidepressants. General anesthesia has an influence on thermoregulatory control. However, temperature regulation during anesthesia in chronically depressed patients remains unclear.
We clinicopathologically studied 23 surgically resected cases of combined hepatocellular and cholangiocarcinoma (HCC-CC). The frequency of this cancer in our subjects, who had primary liver cancer ...and who underwent hepatectomy, was 6.3%. The mean age of patients was 64.0 years old and the male: female ratio was 1.9:1. Serum alpha-fetoprotein was positive in 70% of cases and its levels were relatively low (< or = 1000 ng/mL) in most cases. The positive rate of serum carcinoembryonic antigen was 18% and its levels were also low. In regard to hepatitis virus markers, 17% of the 20 combined HCC-CC cases were positive to HBs antigen and 70% were positive to the HCV antibody. Of the 23 combined HCC-CC cases, 9 cases (39%) were associated with liver cirrhosis. Tumours were classified macroscopically into a separated type (HCC and CC are clearly separated 17%), a HCC-predominant type (resembles HCC 49%), and a CC-predominant type (resembles CC 34%). The separated and HCC-predominant types were associated with liver cirrhosis in 50 and 55% of cases, respectively. These cases with liver cirrhosis presented the features of HCC more apparently, while those without liver cirrhosis presented the features of CC. Histologically, all cases were classified into either Type I (HCC and CC were clearly distinguished; 17%), Type II (HCC and CC were contiguous and shared transitional features; 66%), and Type III (cancer cells were able to be evaluated as either HCC or CC and were considered to be an intermediate type; 17%). Immunohistological stains for cytokeratin were useful to distinguish HCC and CC. Specifically, CC was positive to cytokeratin 7 and 19. The tumour, in which HCC and CC were almost indistinguishable, such as Type III), indicates the presence of intermediate tumour cells that can differentiate either to HCC or CC.
Background: Patients with alcohol problems often develop postoperative confusion and have impaired cortisol, ACTH, and norepinephrine. However, the relationship between neuroendocrine responses to ...surgical stress and postoperative confusion remains unclear in patients with alcohol problems.
Methods: Plasma cortisol, ACTH, and norepinephrine concentrations during and after surgery in 30 patients with alcohol problems and 30 control patients who underwent lower abdominal surgery were measured before the induction of anesthesia, 15 and 60 min after skin incision, 60 min after the end of surgery, the next day, and the second day after the operation.
Results: Plasma cortisol concentrations (21.2 ± 4.7 μg·dl−1) of patients with alcohol problems before anesthesia were significantly higher than 15.6 ± 4.8 μg·dl−1 of control patients. Plasma cortisol and ACTH responses to surgery in patients with alcohol problems were not significantly increased compared with preoperative values. The incidence of postoperative confusion was significantly higher in patients with alcohol problems than that of control patients (33% vs. 3%). Plasma cortisol concentrations (29.7 ± 7.0, 31.2 ± 6.6, 30.3 ± 8.0, and 28.4 ± 6.2 μg·dl−1) 15 and 60 min after the skin incision, 60 min after the end of surgery, and the next day after operation in postoperatively confused patients with alcohol problems were significantly higher than those of nonconfused patients with alcohol problems (23.0 ± 5.8, 22.7 ± 4.1, 22.4 ± 7.2, and 21.9 ± 5.5 μg·dl−1).
Conclusion: The cortisol response to surgical stress increases in patients with alcohol problems who develop postoperative confusion, although cortisol response to surgical stress decreases in patients with alcohol problems without postoperative confusion.
To compare propofol plus spinal anesthesia during spontaneous ventilation using the Laryngeal Mask Airway and propofol plus fentanyl anesthesia during mechanical ventilation with an endotracheal tube ...on quality of recovery after anesthesia.
Prospective, randomized study.
Hirosaki National Hospital.
150 patients (aged > 70 years) undergoing total knee arthroplasty.
Patients were divided randomly into two groups, to receive spontaneous ventilation with a Laryngeal Mask Airway during propofol-spinal anesthesia, or to receive propofol-fentanyl anesthesia with mechanical ventilation via endotracheal tube.
Quality of anesthesia recovery such as nausea, vomiting, headache, pain throat, hoarse voice, back pain, dizziness, feeling comfortable, dreaming, recovery times in recovery of anesthesia, recovery times, postoperative pain, confusion, was assessed.
The frequency of postoperative pain throat, hoarse voice, and nausea was significantly lower in the propofol-spinal anesthesia group than the propofol-fentanyl anesthesia group. The time to extubation, emergence, response to commands, and orientation were significantly faster (
p < 0.001) in the propofol-spinal anesthesia group than the propofol-fentanyl anesthesia group. The frequency of postoperative confusion occurring in the propofol-spinal anesthesia group during the first 24 hours was significantly lower than that of the propofol-fentanyl anesthesia group (
p = 0.03).
Conclusions: Propofol-spinal anesthesia provided better and faster recovery than did propofol-fentanyl anesthesia for elderly patients undergoing total knee arthroplasty.
Osamu Kano,1 Hirono Ito,1 Takanori Takazawa,1 Yuji Kawase,1 Kiyoko Murata,1 Konosuke Iwamoto,1 Tetsuro Nagaoka,1 Takehisa Hirayama,1 Ken Miura,1 Riya Nagata,1 Tetsuhito Kiyozuka,2 Jo Aoyagi,2 Ryuta ...Sato,2 Teruo Eguchi,3 Ken Ikeda,1 Yasuo Iwasaki11Department of Neurology, Toho University Omori Medical Center, 2Department of Neurology, Federation of National Public Service Personnel Mutual Aid Associations Mishuku Hospital, 3Sakura-kai Medical Group, Tokyo, JapanAbstract: Clinical trials have shown the benefits of acetylcholinesterase inhibitors, such as donepezil and galantamine, and an N-methyl-d-aspartate receptor antagonist, memantine, in patients with Alzheimer’s disease (AD). However, little is known regarding the effects of switching from donepezil 5 mg/day to galantamine 16 or 24 mg/day, or regarding the effects of adding memantine to established therapy compared with increasing the dose of donepezil. This report discusses two studies conducted to evaluate treatment with galantamine and memantine with respect to cognitive benefits and caregiver evaluations in patients with AD receiving donepezil 5 mg/day for more than 6 months. Patients with mild or moderate AD (scores 10–22 on the Mini-Mental State Examination) were enrolled in the Galantamine Switch study and switched to galantamine (maximum doses 16 mg versus 24 mg). Patients with moderate to severe AD (Mini-Mental State Examination scores 3–14) were enrolled in the Donepezil Increase versus Additional Memantine study and either had their donepezil dose increased to 10 mg/day or memantine 20 mg/day added to their existing donepezil dose. Patients received the study treatment for 28 weeks and their Disability Assessment for Dementia, Mental Function Impairment Scale, Cohen-Mansfield Agitation Inventory, and Neuropsychiatric Inventory scores were assessed with assistance from their caregivers. For the Galantamine Switch study after 8 weeks, agitation evaluated by the Cohen-Mansfield Agitation Inventory improved in both the 16 mg and 24 mg groups compared with baseline. However, there were no significant differences between the two galantamine groups. Agitation was also less in patients in the additional memantine group than in the donepezil increase group. In summary, switching to galantamine from donepezil and addition of memantine in patients with AD receiving donepezil were both safe and meaningful treatment options, and particularly efficacious for suppression of agitation.Keywords: Alzheimer’s disease, galantamine, memantine, donepezil, agitation, acetylcholinesterase inhibitors
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