No abstract

This study investigated the effects of binaural monopolar galvanic vestibular stimulation (GVS), which likely stimulates the bilateral vestibular system, on the anterior bending angle in patients with Parkinson's disease (PD) with anterior bending posture in a single-blind, randomized sham-controlled crossover trial. The seven PD patients completed two types of stimulation (binaural monopolar GVS and sham stimulation) applied in a random order 1 week apart. We measured each patient's anterior bending angles while he or she stood with eyes open and eyes closed before/after the stimulations. The anterior bending angles in both the eyes-open and the eyes-closed conditions were significantly reduced after the GVS. The amount of change in the eyes-closed condition post-GVS was significantly larger than that by sham stimulation. The amount of change in anterior bending angles in the GVS condition was not significantly correlated with Unified Parkinson's Disease Rating Scale motor score, disease duration, the duration of the postural deformities, and the anterior bending angles before the GVS. Binaural monopolar GVS might improve anterior bending posture in PD patients, irrespective of the duration and the severity of disease and postural deformities. Binaural monopolar GVS might be a novel treatment strategy to improve anterior bending posture in PD.

ObjectiveGalvanic vestibular stimulation (GVS) activates the vestibular afferents, and these changes in vestibular input exert a strong influence on the subject’s posture or standing balance. In patients with Parkinson’s disease (PD), vestibular dysfunction might contribute to postural instability and gait disorders.MethodsCurrent intensity was increased to 0.7 mA, and the current was applied to the patients for 20 minutes. To perform a sham stimulation, the current intensity was increased as described and then decreased to 0 mA over the course of 10 seconds. The patient’s status was recorded continuously for 20 minutes with the patient in the supine position.ResultsThree out of 5 patients diagnosed with PD with postural instability and/or abnormal axial posture showed a reduction in postural instability after GVS. The score for item 12 of the revised Unified Parkinson’s Disease Rating Scale part 3 was decreased in these patients.ConclusionsThe mechanism of postural instability is complex and not completely understood. In 2 out of the 5 patients, postural instability was not changed in response to GVS. Nonetheless, the GVS-induced change in postural instability for 3 patients in our study suggests that GVS might be a therapeutic option for postural instability.

No abstract

No abstract

It is very important to examine the influence of inhibition of in situ estrogen production on the pathobiology of human sex steroid-dependent tumors in order to understand the clinical effects of aromatase inhibitors. We have examined the biological changes before and after aromatase inhibitor treatment in vitro (endometrial and ovarian cancer) and in vivo (breast cancer). First, we analyzed these changes using histoculture of 15 human endometrial cancers and 9 ovarian cancers. Five of the fifteen endometrial cancers and four of the nine ovarian cancers demonstrated decreased [3 H]thymidine uptake or Ki67 labeling index after 14α-hydroxy-4-androstene-3,6,17-trione (NKS01) treatment.In ovarian cancer cases, the responsive cases tended to be associated with higher aromatase and estrogen receptor α (ER) expression compared with the other cases but this was not seen in the endometrial cancer cases. There were no changes in ER and aromatase expression before and after NKS01 treatment in either ovarian or endometrial cancer cases. We then studied the same primary human breast tumors before and after aminoglutethimide (AMG, n=3) and 4-hydroxyandrostenedione (4-OHA, n=3) treatment. Tumor aromatase activity increased in 3 cases and decreased or was unchanged in 3 cases but aromatase immunoreactivity in stroma and adipocytes was unaltered in 5 cases. There were no changes in the ER labeling index before or after treatment. Five of the six cases including the responsive cases tended to be associated with decreased cell proliferation or Ki67 expression and increased apoptosis when examined by the TUNEL method. These results indicate that aromatase inhibitors may exert their effects on human breast and other cancers through Endocrine-Related Cancer (1999) 6 197-204 decreasing proliferation and increasing apoptosis, possibly without altering ER status.

Vascular endothelial growth/permeability factor (VEG/PF) is expressed in some normal tissues and at high levels in a wide range of tumors. This growth factor is believed to be a key mediator of angiogenesis. Recent reports have shown that VEG/PF mRNA in the normal rat uterus is stimulated by estradiol (E2). In this study, we investigated the expression of VEG/PF in the mammary gland and 7,12-dimethylbenz(a)anthracene (DMBA)-induced, hormone-dependent mammary tumor of the rat model, and also whether VEG/PF is regulated by E2. VEG/PF mRNA from tumor extracts was amplified by RT-PCR with VEG/PF primers and generated two main products which corresponded in size to those expected for VEG/PF 164 and 120. In some cases, a third product corresponding in size to that expected for VEG/PF 188 was also generated. No such PCR products were generated from equal amount of RNA from normal mammary tissue, rat brain, or liver. Using immunocytochemistry, VEG/PF expression was detected in the epithelial cells of the tumors. We developed an ELISA assay to measure VEG/PF protein concentrations and found a 4-fold difference between normal mammary glands (1.3 +/- 0.11 ng/mg protein) and tumors (4.44 +/- 0.66) (P < 0.01). E2 treatment (5 microg/rat, s.c.) of rats 24 h after ovariectomy, greatly enhanced the expression of RT-PCR products in tumors within 2 h, which reached a maximum at 6-8 h but declined by 48 h. VEG/PF concentrations were also increased 8-12 h after E2 injection. When rats were given two injections of aromatase inhibitor 4-hydroxyandrostenedione (4-OHA 10 mg/rat s.c.) 24 h apart, to reduce estrogen concentrations, a low level of RT-PCR products was maintained for at least 96 h. After a single injection of 4-OHA, RT-PCR products remained low until 36 h when an increase occurred corresponding with a rise in plasma E2 levels. Injection of E2 2 h after 4-OHA treatment, caused a rise in RT-PCR products in 6-8 h. However, there was no significant change in VEG/PF concentrations. An increase in VEG/PF protein concentrations followed the increase in mRNA levels by 4-6 h. Thus, it appears that E2 causes a rapid induction of VEG/PF expression in mammary tumors that is similar to that observed in the normal uterus. These findings suggest that one mechanism by which estrogen acts as a mammary tumor promotor is by stimulating VEG/PF, leading to increased tumor angiogenesis and/or permeability of the microvessels to allow tumor cell migration.

No abstract