Effect of yokukansan on the behavioral and psychological symptoms of dementia in elderly patients with Alzheimer's disease

Objective

The aim of this study was to investigate the effects of yokukansan (YKS) on the behavioral and psychological symptoms of dementia (BPSD) in elderly patients with Alzheimer's disease (AD).

Methods

Fifteen patients with AD (mean age: 80.2 ± 4.0 years) participated in the study. The Mini-Mental State Examination (MMSE) was used for the assessment of cognitive function. BPSD were evaluated using the Neuropsychiatric Inventory (NPI). The Barthel Index was used for the assessment for the activities of daily living (ADL). The treatment with YKS along with sulpiride, a dopamine D₂ selective antipsychotic, was performed for 12 weeks.

Results

Fourteen patients completed the trial. After the 12 weeks of treatment with YKS, significant improvement of the mean NPI score was observed while no significant improvement was observed in the control group. The average dose of sulpiride at the end of the present study was less in the YKS group than in the control group. The MMSE results did not change either in the YKS group or in the control group. The Barthel Index did not significantly change either in the YKS group or in the control group. No serious adverse effects were noted.

Conclusions

Twelve weeks of the YKS treatment significantly improved BPSD with less antipsychotics in elderly patients with AD. The YKS treatment did not cause any cognitive decline or ADL decline and no serious adverse effects were noted. The present study suggests that YKS is beneficial for the treatment of BPSD and that it can possibly reduce the doses of antipsychotics required for the treatment of BPSD. Further studies with larger patient populations using a double-blind placebo-controlled design should be performed.     

A primary gastric adenosquamous carcinoma with remarkable lymphatic metastasis diagnosed by the stomach and lymph node biopsy

This report describes the case of a 74-year-old female, who had been admitted to hospital because of epigastralgia and appetite loss. An ultrasonogram and a CT scan of the abdomen revealed a remarkable lymph node metastasis. Through an upper gastrointestinal tract (UGI) X-ray, a Borrmann III type gastric carcinoma was detected. Under endoscopic guidance, a gastric and a lymph node specimen were taken and biopsied, revealing a keratinous, well-differentiated squamous cell carcinoma and a poorly differentiated adenocarcinoma, leading to a diagnosis of a primary gastric adenosquamous carcinoma with a remarkable lymphnode metastasis. After chemotherapy, a CT scan, a UGI X-ray, and an endoscopic examination revealed distinct tumor reduction.     

Videofluorography of the pharynx in patients suffering from aspiration pneumonia

We evaluated videofluorographic recordings of the pharynx (VF) in patients suffering from aspiration pneumonia. The patients consisted of 55 men and 6 women who consulted the ENT Department at Kumamoto University Hospital between May 1994 and February 2002. Surgery for an upper alimentary tract malignancy (16 patients) was the most frequent background feature. The number of patients with cerebrovasucular disease and neuronal/neuromuscular diseases were 11 and 12, respectively. VF enabled the misswallowing of barium into the trachea to be visualized in 38 patients. Of these 38 patients, 20 exhibited misswallowing during or after the pharyngeal stage of swallowing. Among the 23 patients in whom misswallowing was not detected, 13 had upper alimentary tract diseases. The VF findings suggested the presence of gastroesophageal clearance after swallowing. Gastro-esophageal regurgitation may be a significant factor, in addition to the silent aspiration of oral and pharyngeal secretions during the night as a trigger of recurrent aspiration pneumonia.     

The improvement of quality of life of patients with aspiration pneumonia after surgical therapy for intractable aspiration

Sixteen patients with recurrent aspiration pneumonia that could not be controlled by appropriate medical therapies. These patients had no hope of recovering laryngeal function. Eight underwent laryngectomy, six underwent laryngotracheal separation and four underwent tracheoesophageal anastomosis. After surgery, we evaluated the efficacy of the therapy and the patients' satisfaction with therapy. Before and after surgery, the following clinical markers were examined to evaluate the efficacy of surgery: scores of aspiration pneumonia, WBC count, C-reactive protein, erythrocyte sedimentation rate, hematocrit, body mass index, total protein, albumin, and the Barthel index, an indicator of daily activity. Furthermore, the grade of Depression and mood, and satisfaction of patients and their carers among family members were scored using the Zung self-rating depression scale, a 20-picture face scale, the visual analog scale, and feeding status. After surgical therapy, we confirmed that aspiration was prevented in fourteen patients of sixteen, and the state of inflammation and nutrition, the state of depression and mood were improved. Thirteen patients from sixteen were able to ingest a meal orally. The quality of life of patients with intractable aspiration was improved.     

Synthetic decarboxylated S-adenosyl-L-methionine as a substrate for aminopropyl transferases

Synthetic decarboxylated S-adenosyl-L-methionine (dcAdoMet), a mixture of the absolute configuration of S and R at the sulfonium center, was evaluated as a substrate for the measurement of spermidine synthase activity. The diastereomers were separated by HPLC with an isocratic elution, and the constant for racemization at the sulfur was determined to be 2.4x10(-6) s(-1) at 37 degrees C and pH 1.5 for the first-eluted biologically active isomer (S-dcAdoMet) and 2.0x10(-6) s(-1) for the second-eluted biologically inactive isomer (R-dcAdoMet). The peak area ratio of S-dcAdoMet to R-dcAdoMet of 48 to 52 in HPLC supported the different racemization constants. Similar substrate activity of dcAdoMet to that of S-dcAdoMet was demonstrated by enzymatic spermidine synthesis. It was shown from the result that the racemized [methyl-(14)C]dcAdoMet prepared in this report was useful for measuring spermidine synthase activity.     

Cytokine production in chorioamnionitis

Lymphohematopoietic cytokines play a significant role in many biological mechanisms including a number of reproductive processes such as ovulation, implantation, placentation, cervical dilation and parturition. Recent experiments have suggested that cytokines play a crucial role in the mechanisms of preterm labor and delivery, which are the leading causes of perinatal morbidity and mortality. Growing evidence suggests that infection is deeply concerned in the pathogenesis of preterm labor and delivery. Chorioamnionitis, a subset of intrauterine infection, has been identified in 20-33% of women with preterm delivery, and the inflammatory and related cytokines, interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8), showed substantial increases in the amniotic fluid at women with intrauterine infection. Although the precise mechanism for chorioamnionitis-driven preterm labor mediated via cytokines is still unknown, both IL-1 and TNF-alpha along with IL-6 enhance prostaglandin production by human amnion cells, chorionic cells and decidual cells. Analysis of the regulatory sequences in the 5' upstream regions of receptor gene for human oxytocin, a potent uterotonic agent, suggests a close relationship between preterm labor and inflammatory cytokines through induction at the oxytocin receptor. Prompt identification of the patients with intra-amniotic infection may be useful in clinical practice. At present, the measurement of IL-8 in maternal serum or the measurement of IL-6 in cervical secretion may be helpful as a non-invasive screening for chorioamnionitis.     

Concurrent chemoradiation therapy with nedaplatin for high-risk cervical cancer--clinical investigation of adverse events

A clinical investigation of adverse events was conducted to confirm the safety of concurrent chemotherapy using nedaplatin (cisplatin derivative) and radiotherapy in the high-risk carcinoma of the uterine cervix. Seven patients who were treated with radical radiotherapy and 5 patients who were treated with adjunctive radiotherapy after radical hysterectomy and pelvic lymphadenectomy were eligible for the study. Nedaplatin was given intravenously at 70 mg/m2 on day 1 and day 29, and a total of 24 courses of nedaplatin administration were observed. None of the planned radiotherapy was postponed or discontinued due to side effects. Major adverse effects observed were gastrointestinal effects such as anorexia (66.7%), nausea and vomiting (33.3%) and diarrhea (66.7%). Grade 3 (in the 2nd course) and Grade 4 (in the 1st course) diarrhea was observed in one patient, which was easily relieved by antidiarrheal. Hematologic side effects were also major, including leukopenia (62.5%), neutropenia (75.0%), anemia (75.0%), and thrombocytopenia (33.3%). Hematologic effects were generally moderate; no Grade 4 (severe) effects were observed. Although these hematologic effects were lasting longer compared with radiation therapy alone, there were no significant differences in the seriousness of these side effects. Concurrent chemoradiation therapy with nedaplatin 70 mg/m2 every 4 weeks was safe and adverse effects were self-limited or resolved with medical management. Dose escalation in the phase III clinical study may be considered.     

Bioavailability and pharmacokinetics of oral dopamine in dogs

The bioavailability and pharmacokinetics of oral dopamine (DA) were studied in dogs. Plasma concentrations of DA and its main metabolites, such as dopamine-3-O-sulfate (DA-SO4) and 3,4-dihydroxyphenyl acetic acid (DOPAC) were determined after intravenous or oral administration of DA using high-performance liquid chromatography with electrochemical detector (HPLC-ECD). Following the intravenous administration, plasma DA-SO4 and DOPAC concentrations were lower than the plasma DA concentration. On the other hand, following the oral administration, plasma DA-SO4 and DOPAC concentrations were much higher than the plasma DA concentration. The absolute bioavailability of DA after oral administration was calculated to be approximately 3%. Intraduodenal and mesenteric venous administration of DA revealed that DA-SO4 was mainly produced in the intestine and DOPAC was produced in the intestine and liver. On the basis of these observations, the bioavailability and pharmacokinetics of oral DA are discussed in connection with the metabolic inactivation due to first-pass metabolism.