Improvement of treatment outcomes after implementation of comprehensive pharmaceutical care in breast cancer patients receiving everolimus and exemestane.

Combination therapy with everolimus and an aromatase inhibitor such as exemestane is an effective treatment option for advanced or recurrent breast cancer. However, the therapy is often limited because of the occurrence of severe adverse events (AEs), including oral mucositis, interstitial lung disease, diarrhea, and rash. Therefore, early management of AEs is extremely important to obtain maximum treatment outcome. We investigated here the effects of comprehensive pharmaceutical care for prevention of severe AEs on patient's quality-of-life (QOL) and continuation of therapy. QOL was assessed every month based on the five-level version of EuroQol-5-Dimension (EQ-5D-5L). AEs were graded according to the Common Terminology Criteria for Adverse Events (ver 4.0). Implementation of comprehensive pharmaceutical care remarkably reduced the incidence of severe oral mucositis as compared with those without such interventions. EQ-5D-5L health states were almost constant during 6 months after intervention, ranging from 0.850 to 0.889. Median time to treatment failure (TTF) was significantly longer after intervention than before [224.0 days, 95% confidence interval (CI): 117-331 days versus 34 days, 21-47 days, hazard ratio (HR): 0.027, 95% CI: 0.005 - 0.154, p<0.001]. These findings suggest that our comprehensive pharmaceutical care is highly effective for enhancing treatment outcome by maintaining patient's QOL.

Anti-inflammatory sesquiterpenes from Curcuma zedoaria.

From the methanolic extract of the rhizome of Curcuma zedoaria, we isolated anti-inflammatory sesquiterpene furanodiene (1) and furanodienone (2) along with new sesquiterpene compound 3 and known eight sesquiterpenes, zederone (4), curzerenone (5), curzeone (6), germacrone (7), 13-hydroxygermacrone (8), dehydrocurdione (9), curcumenone (10), and zedoaronediol (11). Their structures were elucidated on the basis of spectroscopic data. The anti-inflammatory effect of isolated components on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation of mouse ears were examined. Compounds 1 and 2 suppressed the TPA-induced inflammation of mouse ears by 75% and 53%, respectively, at a dose of 1.0 micromol. Their activities are comparable to that of indomethacin, the normally used anti-inflammatory agent.

Influence of location of acceleration sensor on physiological tremor of upper limb.

The physiological tremor of the upper limb in three positions of pronation, neutrality, and supination due to the movement of forearm was measured on four locations at the tip of the finger, the root of the finger in the hand, the wrist, and the elbow with use of an accelerated sensor. The evaluation of the total power, which was the summation of the power spectrum in the frequency range from 1 to 50 Hz, showed no significant difference in any of the positions. The maintenance of the upper limb at the horizontal level showed the coordination of the central nervous system due to the body parts of the upper arm, forearm, hand, and finger connected by the joint. The coherence spectra showed clear activation of the joint of the wrist in the main peak frequency of around 2.5 and 12.5 Hz in their respective positions. The value of the correlation coefficient in the location between the hand and finger was the largest at over 0.8, and those of the locations which connected the joint of the wrist between the forearm and hand and between the forearm and finger were significantly large with a value from 0.6 to 0.8. The mean time (i.e., arrival time) of the transmission from the proximal side (i.e., upper arm and forearm) to the distal side (i.e., hand and finger) in the upper limb was evaluated quantitatively to be 20 ms for pronation and supination, but the value was small for neutrality.

Cortical potentials associated with voluntary, reflex, and spontaneous blinks as bilateral simultaneous eyelid movement.

Movement-related cortical potentials (MRCPs) associated with the contraction of m. orbicularis oculi related to three types of blinks (voluntary, reflex, and spontaneous) were measured for 12 normal subjects. The purpose of the present study was to estimate the role of the cerebral cortex in close association with the blinks caused by bilateral simultaneous eyelid movements. MRCPs were recorded by surface electrodes placed over the frontal to the parietal regions. The mean amplitude and the duration of the MRCPs for the three types of blinks were evaluated by an averaging technique for each subject. MRCPs for the voluntary blinks were evoked in all subjects. For the reflex and the spontaneous blinks, however, a clear negative rising deflection from the baseline was not obtained. The maximum amplitude of the MRCPs for the voluntary blinks was localized at the vertex region, though there was no significant difference between the durations of the MRCPs for the vertex region and for the other regions. Moreover, the positive potential following the voluntary and the spontaneous blinks was recognized in the parietal region. These results suggest that only the voluntary blinks are caused by the neural activation of the supplementary motor area (SMA), and in addition, the neural activation related to visual recognition is considered to be elicited by the voluntary and the spontaneous blinks.

Evaluation of postural tremor of finger for neuromuscular diseases and its application to the classification.

The purpose of this study is to verify the features of the power spectrum of postural tremors for neuromuscular disease patients and to classify the postural tremors. The subjects were 88 neuromuscular disease patients (30 Parkinson disease (PD), 25 cerebellar disease (CER), 7 multiple sclerosis (MS), 7 neuropathy (NEU), 10 motor neuron disease (MND), 9 myopathy (MYO)). The control subjects were 12 normal young persons and 10 normal aged persons. Postural tremor was detected by accelerator sensor. Postural tremor was recorded under the two postural conditions: The subjects maintained the index finger without or with a weight load of 50 g in a horizontal position while looking at a visual target in front of the tip of the index finger. The power spectrum was calculated by an auto-regressive model (AR model). The peak frequency and the peak power were evaluated under the two conditions. Two frequency components of 8-12 Hz and 20-25 Hz appeared in the postural tremor of both normal subjects and neuromuscular disease patients. The difference of the postural tremor between the subjects mainly appeared in the 8-12 Hz component during the postural tremor with a weight load. MYO patients belonged to one group (called as group P1) due to lower peak power, CER patients belonged to one group (called as group P2) due to higher peak power, and PD and MS patients belonged to one group (called as group P3) due to lower peak frequency and higher peak power. NER and MND patients belonged to one group (called as group N which meant normal group). These results suggested that the peak frequency and the peak power of the 8-12 Hz component were changed by the conditions of both spinal reflex system and central nervous system. An oscillator within the central nervous system produced the underlying frequency of 8-12 Hz component, while the amplitude of 8-12 Hz component was governed by both spinal reflex system and central nervous system. In conclusion, the classification of postural tremor for neuromuscular disease patients was a useful index to elucidate the mechanism of tremor oscillation and to assist in clinical diagnosis of neuromuscular disease.

Judgment of disability stages in Parkinson disease patients due to pathological tremor of index finger.

The purpose of this study is to investigate the disability stages of Parkinson disease (PD) patients by wave analysis of parkinsonian pathological tremor. Physiological tremor and pathological tremor for the index finger are detected by accelerator sensor. The power spectrum is calculated by an auto-regressive model (AR model). The peak frequency and the peak power of the tremor for the index finger are evaluated under two conditions: (1) maintaining the index finger in a horizontal position using visual feedback with or without a weight load of 50 g, in which tremor is referred to as postural tremor, (2) resting the index finger with eyes closed, in which the tremor is referred to as resting tremor. The physiological tremor and the pathological tremor for the finger are characterized by two peak frequency components in which the first peak frequency component is 8-12 Hz, and the second is 20-25 Hz under the two conditions stated above. The peak frequency and the peak power for the PD patients at the two peak frequency components show the characteristics for the disability level of the PD patients. The first peak power especially around 8-12 Hz in the postural tremor without and with the weight load significantly increases as the disability stage determined by the Hoehn-Yahr method worsens, and there is significant difference of the peak powers for the stages. These results suggest that the first peak power around 8-12 Hz for the postural tremor without and with the weight load is a useful index to judge PD disability stage. It is found that postural tremor without and with the weight load gives the significant peak frequency and peak power compared with those for normal persons. It is pointed out that the first peak frequency component of 8-12 Hz originates from the central nervous system, and the first peak power reflects the degrees of disorder in the central nervous system, since PD is caused by the functional lowering of the central nervous system.

Synthesis of Squamostanal-A.

The first synthesis of squamostanal-A (1), separated as a degradation product of tetrahydrofuranic acetogenins, is described. Iodide 7, which corresponds to the latent aldehyde moiety of 1, was prepared through a 2-step sequence from 13-[tetrahydropyran-2'- yloxy]-2-tridecyn-l-ol (5). The NaHMDS-based coupling reaction of 7 with γ-lactone 8 gave compound 9, which by a 3-step sequence, was coverted to 1.

Synthesis of (-)-muricatacin.

The synthesis of (-)-muricatacin starting from 1-bromododecane and 2-pentyn-1-ol is described. 2-Pentadecyn-1-ol (4), which was prepared from 1-bromododecane (2) and 2-pentyn-1-ol (3), was converted to epoxy alcohol 6 through a two-step reaction sequence, 6 being successively submitted to tosylation, iodination, chain extension with tert-butyl lithioacetate, and acid-catalyzed cyclization to give (-)-muricatacin (1a). Recrystallization afforded optically pure 1a.