Long-term vardenafil therapy improves hemodynamics in patients with pulmonary hypertension.

The phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, has been reported to produce sustained pulmonary vasodilatation in patients with pulmonary hypertension (PH). Recently, vardenafil, a more potent and selective PDE-5 inhibitor than sildenafil, has been approved for the treatment of erectile dysfunction. However, the long-term effects of oral vardenafil in patients with PH are unknown. We studied five consecutive patients with PH; one with primary pulmonary hypertension, two with chronic pulmonary thromboembolism, one with Eisenmenger syndrome (ventricular septal defect) and one with secondary pulmonary hypertension after a ventricular septal defect closure operation. In an acute hemodynamic trial, vardenafil (5 mg) significantly decreased both the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with an increase in cardiac output. In a chronic hemodynamic trial, the maintenance dose of vardenafil (10 to 15 mg) for 3 months significantly decreased the PVR, but not the SVR, with a 20.7% reduction of the PVR/ SVR ratio. Plasma brain natriuretic peptide (BNP) levels were also significantly decreased after 3 months. This pilot study demonstrates that long-term oral vardenafil therapy may be a safe and effective treatment for patients with PH.     

Pedaling automatism in atypical West syndrome: a case report]

A seven-month-old girl with atypical West syndrome with pedaling automatism was reported. She started to have early infantile epileptic encephalopathy with suppression-burst (EIEE) at age 14 days followed by infantile spasms at 3 months of age. She began to have spasms with automatism at 4 month, mainly consisting of pedaling movements of both feet associated with tonic spasms of upper extremities and writhing of trunk. Ictal EEG showed irregular slow waves with occasional spikes predominantly over the right hemisphere mixed with artifacts. Interictal EEG during sleep showed suppression-burst patterns. Cerebral atrophy and microcephaly were revealed on brain CT, immature myelination on MRI and decreased blood flow in the frontal, temporal, and parietal lobes on the right on PET scan. Pedaling automatism is rare in infancy and its clinical significance was discussed in relation to West syndrome and complex partial seizures.     

A clinical trial of low dose methotrexate therapy in patients with rheumatoid arthritis]

The efficacy and safety of MTX in active RA were evaluated based on patient medical records. The study population consisted of 460 patients with active RA who had received no prior MTX therapy and started it at our hospital between August 1998 and December 2003 (80 men and 380 women with a mean age of 59.3 years). After 24 weeks of MTX therapy, 61.3% of patients showed a 20% improvement, and 30.4% achieved a 50% improvement according to the ACR criteria. The cumulative rate of patients who continued MTX therapy for 48 weeks was 0.567. During the observation period, 260 patients (56.5%) experienced 304 adverse reactions. 52 patients (11.3%) discontinued treatment because of adverse reactions, and 10 patients (2.2%) died. The adverse reactions that occurred in at least 1% of patients were: abnormal hepatic function (31.7%), infection (6.1%), gastrointestinal symptoms (5.0%), stomatitis (3.9%), hematological abnormalities (3.5%), fracture (3.5%), malignant tumor (2.6%), interstitial pneumonia (2.0%), cerebrovascular or cardiovascular disorder (2.0%), headache (1.7%), eruption (1.3%), and alopecia (1.1%). Adverse reactions were more common in the elderly and patients with advanced stage disease. This study reaffirms the therapeutic benefit of MTX, but suggests that careful monitoring is of great importance.     

Study on effects of life review activities on the quality of life of the elderly: a randomized controlled trial

BACKGROUND: The objective of this study was to evaluate the mid-term efficacy of life review activities on the quality of life (QOL) of the elderly by conducting a randomized controlled trial, and to identify the factors that should be taken into consideration when conducting life review activities. METHODS: Written consent was obtained from 80 of the 97 eligible elderly persons. After randomly assigning them to two groups, an intervention group and a control group, group life review activities were conducted in the intervention group and discussion activities about health were conducted in the control group. In both the intervention group and the control group, life satisfaction, self-esteem, depression, and hopelessness were evaluated using self-rating scales at three points: at baseline, immediately after completion of the 8 weeks of sessions, and 3 months after completion of the intervention. RESULTS: Repeated measures analysis of covariance showed significant differences between the two groups in the changes in scores for depression (p = 0.04) and hopelessness (p = 0.04). Regarding the factors that were associated with depression and hopelessness, 3 months after completion of the intervention, depression and hopelessness of a more severe nature at baseline and having greater unresolved conflicts in the past were extracted by multiple regression analysis. CONCLUSIONS: The results suggested that group life review activities have a role in assisting the developmental stage of old age and supporting mental health, and have mid- to long-term effectiveness in maintaining and improving the QOL of the elderly.     

The effects of high dose of parathyroid hormone on fetal osteoclasts and their precursors in vivo: An ultrastructural-cytochemical study

Background: It is not well known how the immediate precursors of osteoclast develop into osteoclasts in the fetus. This ultrastructural-cytochemical study was designed to clarify the formation process of the osteoclasts and their increased activities in the fetal mouse limb buds after administration of high dose parathyroid hormone (PTH). Methods: Twenty-four or forty-eight hours after the high doses of PTH were injected into amniotic fluid of the pregnant C₃H mice, the femoral limb buds of embryos were dissected out. Tartrate-resistant acid phosphatase (TRAP) reactions were performed while preparing specimens for electron microscopy. Results: Both control and PTH-given preosteoclasts and osteoclasts exhibited TRAP-positivities in dense bodies and vesicles. As effects of PTH, a binucleated preosteoclast of tandem fashion was observed. More osteoclastic hyperactivities were observed in the diaphyseal bone marrow. An osteoclast with a large cytoplasm exhibited two sets of clear zones and ruffled borders. Some osteoclasts demonstrated prominent amoeboid figures, while other osteoclasts developed large cytoplasmic vacuoles, which contained pieces of calcified chondroid bars. Conclusions: Our results revealed the progression of maturation from young preosteoclasts to osteoclasts. An existence of a peculiar binucleated preosteoclasts suggested one of the processes for multinucleation of the osteoclast. Quite remarkable osteoclastic hyperactivities were obviously the effects of high dose PTH. Our results also indicated the endophagocytic ability of the osteoclast. How PTH affected the osteoclasts and their precursors in the diaphyseal bone marrow can be speculated. © 1995 Wiley-Liss, Inc.     

Alcohol consumption, smoking, and subsequent risk of colorectal cancer in middle-aged and elderly Japanese men and women: Japan Public Health Center-based prospective study.

Few studies have examined the association of alcohol consumption and cigarette smoking with colorectal cancer in Asian populations whose genetic susceptibility to these factors are different from Western populations. We investigated this association and the joint effect of these factors, and estimated the population-attributable fraction to clarify the public health impact on a Japanese population, based on a prospective study. We analyzed the 10-year (cohort I) and 7-year (cohort II) follow-up data of the Japan Public Health Center-based prospective study on cancer and cardiovascular disease, derived from 90,004 (42,540 male and 47,464 female) middle-aged and elderly Japanese. We identified 716 (457 in men and 259 in women) newly diagnosed cases of colorectal cancer. Both alcohol consumption and smoking were clearly associated with colorectal cancer in men, after adjusting for age, family history of colorectal cancer, body mass index, and physical exercise. Regular heavy drinking of 150 g/week or more of ethanol showed a statistically significant increased risk compared with nondrinkers: relative risks (RRs) were 1.4 [95% confidence interval (CI), 1.1-1.9] for 150-299 g/week and 2.1 (95% CI, 1.6-2.7) for 300 g/week or more. On the contrary, regular ethanol consumption was not associated with colorectal cancer (RR, 0.7; 95% CI, 0.4-1.1) in women. In terms of smoking, the RRs were 1.4 (95% CI, 1.1-1.8) for current smokers and 1.3 (95% CI, 0.98-1.7) for ex-smokers compared with never-smokers in men. The risk of smoking in women was similar to that in men, although not statistically significant. The colorectal cancer risk with 300 g/week or more of ethanol in current smokers was estimated at 3.0 (95% CI, 1.8-5.1) compared with nondrinkers among nonsmokers in men. Colorectal cancer attributable to alcohol consumption or smoking was estimated to be 46%. In conclusion, approximately half of the colorectal cancer cases may be preventable by tobacco and alcohol controls in middle-aged and elderly Japanese men.     

Anesthesia for a cervical myelopathy patient with tracheal stenosis

A 71-year-old male with cervical myelopathy was scheduled for C 3-7 laminectomy. Once he had been rejected of general anesthesia in other hospital because of his tracheal stenosis. The diameter of the narrowest part of his trachea was 5 mm probably resulting from tracheostomy at 2 years of age. His cervical myelopathy seemed to be no problem for anesthesia induction because he had no problems in his neck movement and opening mouth. We evaluated his tracheal stenosis carefully using bronchofiberscopy, chest X-ray, computed tomography and pulmonary function tests. After intravenous fentanyl 100 micrograms and midazolam 2.5 mg, it was impossible to ventilate the patient. Therefore, tracheal intubation was performed immediately after lidocaine administration into the trachea. During surgery, tracheal tube dilated the narrowed portion. After surgery, the tracheal tube was removed under bronchofiberscopic observation without any problems. Tracheal stenosis was observed by chest X-ray after surgery, but he had no complaints.     

Combined intercostal nerve block and epidural anesthesia in a patient with severe aortitis syndrome

A 74-year-old woman with aortitis syndrome was scheduled for mastectomy. Her left vertebral artery was totally occluded and left carotid arteries, left subclavia artery and bilateral common renal arteries were occluded. For anesthesia a catheter was inserted into the epidural space between T3 and T4. Lidocaine 80 mg (2%, 4 ml) was administered epidurally. Then intercostal nerve block was performed with bupivacaine 15 mg (0.5%, 3 ml) at T3 and T4 level. Local infiltration of lidocaine 50 mg (1%, 5 ml) was added. During the surgery, hemodynamics were stable and no neurological symptom was observed. Epidural anesthesia alone might be sufficient for anesthesia if higher concentration of local anesthetic was used. However, to avoid hemodynamic change, we used 1% lidocaine and added intercostal nerve block. We conclude that combined intercostal nerve block and epidural anesthesia was useful for a patient with severe aortitis syndrome in oder to monitor consciousness to detect cerebral ischemia and to avoid hemodynamic instability.     

Anesthetic management for MIDCAB using the target controlled infusion and the bispectral index

We report our experience in using the target controlled infusion (TCI) of propofol combined with the bispectral index (BIS) monitoring for anesthetic management of minimally invasive direct coronary artery bypass (MIDCAB) in a 43-year-old-male patient with angina pectoris. After premedication, the patient was connected to the monitor with electrodes for BIS monitor. Then, anesthesia was induced with fentanyl and propofol using TCI technique. When blood concentration of propofol reached 4 micrograms.ml-1, the trachea was intubated. Before starting the operation, we evaluated the relationship between blood concentration of propofol and the value of BIS, and the standard maintenance concentration of propofol was set at 3 micrograms.ml-1. When the concentration of propofol was 3 micrograms.ml-1, the value of BIS was about 60. Anesthesia was maintained with nitrous oxide and oxygen and continuous infusion of propofol using TCI technique. When necessary, we gave additional injection of fentanyl and vecuronium bromide. Furthermore, diltiazem was infused continuously for cardiac rate control, as well as infusion of nicorandil, nitroglycerine for prevention of coronary artery spasms, and prostaglandin. After the operation, the patient was alert in 8 minutes and we could extubate in 12 minutes. The use of TCI combined with BIS monitoring for maintenance of anesthesia for MIDCAB is useful and safe.     

The comparison of effects of processed Aconiti tuber, U50488H and MK-801 on the antinociceptive tolerance to morphine

In the previous studies, we demonstrated that an oriental herbal medicine, processed Aconiti tuber (PAT), at subanalgesic doses could inhibit or reverse the antinociceptive tolerance to morphine. In the present study, we compared the effect of PAT, trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidin)cyclohexyl)-benzeneacetamide methane sulfonate hydrate (U50488H), a selective kappa opioid receptor (KOR) agonist, and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine-maleate (MK-801), a N-methyl-D-aspartate (NMDA) receptor antagonist, on the antinociceptive tolerance to morphine in the same experimental condition. Mice received subcutaneous morphine (10 mg/kg), and oral PAT at a subanalgesic dose (0.3 g/kg for mechanical or 1.0 g/kg for thermal test), or intraperitoneal U50488H at a subanalgesic dose (3 mg/kg), or MK-801 at a subanalgesic dose (0.1 mg/kg) once daily for 14 days. The mechanical nociceptive threshold was measured before, and at 60 min by tail pressure testing, and thermal nociceptive latency was measured before, and at 30 min by hot plate testing, after daily morphine injections. PAT and U50488H could not only inhibit the development of morphine tolerance but also reverse the already-developed morphine tolerance, while MK-801 could only inhibit the development of morphine tolerance but not reverse the already-developed morphine tolerance, in both mechanical and thermal nociceptive tests. These data suggested that PAT, an indirect-acting KOR agonist, share the common pharmacological property of KOR agonists on morphine tolerance, and that PAT may be superior to some NMDA receptor antagonists which do not reverse already-developed morphine tolerance.