In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease

Clinical symptoms of Parkinson's disease (PD) do not manifest until dopamine (DA) neuronal loss reaches a symptomatic threshold. To explore the mechanisms of functional compensation that occur in presynaptic DA nerve terminals in PD, we compared striatal positron emission tomographic (PET) measurements by using [11C]dihydrotetrabenazine ([11C]DTBZ; labeling the vesicular monoamine transporter type 2), [11C]methylphenidate (labeling the plasma membrane DA transporter), and [18F]dopa (reflecting synthesis and storage of DA). Three consecutive PET scans were performed in three-dimensional mode by using each tracer on 35 patients and 16 age-matched, normal controls. PET measurements by the three tracers were compared between subgroups of earlier and later stages of PD, between drug-naive and drug-treated subgroups of PD, and between subregions of the parkinsonian striatum. The quantitative relationships of [18F]dopa and [11]DTBZ, and of [11C]methylphenidate and [11C]DTBZ, were compared between the PD and the normal control subjects. We found that [18F]dopa Ki was reduced less than the binding potential (Bmax/Kd) for [11C]DTBZ in the parkinsonian striatum, whereas the [11C]methylphenidate binding potential was reduced more than [11C]DTBZ binding potential. These observations suggest that the activity of aromatic L-amino acid decarboxylase is up-regulated, whereas the plasma membrane DA transporter is down-regulated in the striatum of patients with PD.     

Staying Connected While Nurturing an Infant: A Challenge of New Motherhood*

Abstract: Fifteen at‐risk new mothers participating in a volunteer home‐visiting program were interviewed about their experiences with these home‐visitors and their relationships with close family and friends after their babies were born. Results of the qualitative analysis, viewed through the lens of Relational Cultural Theory (RCT), detail the social isolation and personal disconnection that they experienced. Their narratives also provide insights about the volunteers’ use of techniques—such as validation, affirmation, consistency, and emotional and instrumental aid—to enhance the mothers’ self‐confidence in caring for their babies, to reduce painful feelings, and to increase interpersonal connections. Recommendations are included for working with couples anticipating a new baby.     

The centrosome and the DNA damage induced checkpoint

The centrosome, the microtubule-organizing center of the cell, acts as a localization point, where signaling molecules are able to interact. Many kinases and phosphatases critical for regulation of DNA damage signaling pathways localize to the centrosome. This review will discuss the possible involvement of the centrosome in mediating DNA damage checkpoint control, in particular the effect of DNA damage signaling pathways involved in initiation or maintenance of cell cycle arrest on the centrosome. The mechanisms that lead to centrosome abnormalities such as centrosome hyperamplification and multipolarity in response to DNA damage will also be addressed.     

Surgical treatment of the diabetic foot

The majority of patients with diabetic foot problems can be treated non-surgically. In this article a short overview is given of the surgical procedures employed in the salvage of the diabetic foot with discussion of the indications and techniques.     

Combined pars plana vitrectomy and cataract surgery: outcome of phacoemulsification versus manual extracapsular cataract extraction through a sclerocorneal tunnel.

BACKGROUND AND OBJECTIVE: To compare the results of combined pars plana vitrectomy and cataract extraction with intraocular lens implantation by phacoemulsification versus manual extracapsular cataract extraction through a sclerocorneal tunnel. PATIENTS AND METHODS: Retrospective chart review of all patients who underwent combined pars plana vitrectomy with intraocular lens implantation and phacoemulsification or extracapsular cataract extraction through a sclerocorneal tunnel between March 1992 and July 2002. RESULTS: Fifty-four eyes of 51 patients were evaluated. Mean age was 69.68 +/- 9.11 years, and mean follow-up was 9 months. Phacoemulsification was performed in 35 cases (64%) and manual extraction in 19 cases (36%). Visual acuity improved from mean logarithm of the minimal angle of resolution 1.69 +/- 0.54 before surgery to 1.22 +/- 0.76 after surgery. There was a greater improvement of visual acuity in the phacoemulsification group (0.59 +/- 0.67) than in the extracapsular cataract extraction group (0.22 +/- 0.68) (P = .06). Final visual acuity was correlated to the vitreoretinal pathology. Ultrasound biomicroscopy showed well-positioned foldable or rigid intraocular lens in the bag or in the sulcus. CONCLUSION: Combined cataract extraction by phacoemulsification or extracapsular cataract extraction through sclerocorneal tunnel and pars plana vitrectomy are safe and effective procedures.     

Combined photodynamic therapy and intravitreal triamcinolone acetonide injection for neovascular age-related macular degeneration with pigment epithelium detachment.

BACKGROUND AND OBJECTIVE: To report the outcome of combined verteporfin photodynamic therapy (PDT) and intravitreal triamcinolone acetonide (IVTA) for the treatment of choroidal neovascularization (CNV) with serous pigment epithelium detachment (PED) due to age-related macular degeneration (AMD). PATIENTS AND METHODS: The files of all consecutive patients with CNV and serous PED who received PDT and IVTA either primarily (primary treatment group) or following previous unsuccessful PDT (secondary treatment group) were reviewed for visual and angiographic results. RESULTS: Ten patients (11 eyes) were included. Mean number of PDT sessions was 3.18; 8 eyes received one IVTA injection and 3 eyes received two IVTA injections. Thirty-six percent of patients retained their initial visual acuity after a mean follow-up of 15.3 months. Loss of 3 or more Snellen lines was noted in 2 of 3 eyes in the primary treatment group and 5 of 8 eyes in the secondary treatment group. Increased intraocular pressure developed in 3 patients and was controlled by topical medications. CONCLUSIONS: Although combined PDT and IVTA may be considered for CNV with serous PED in patients with poor prognosis with PDT alone, the regimen as administered in this small series was not beneficial. Further studies are required to determine whether alternate sequences, timing, or doses would yield a better outcome.     

Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction.

PURPOSE: Locoregional recurrence is the dominant form of treatment failure in head and neck (H&N) cancer. The epidermal growth factor receptor (EGFR) is frequently amplified in this disease (相似文献   

Effects of a new clinically relevant antiestrogen (GW5638) related to tamoxifen on breast and endometrial cancer growth in vivo.

PURPOSE: Cross-resistance is an important issue for the evaluation of new antiestrogens to treat advanced breast cancer patients who have failed tamoxifen therapy. In addition, postmenopausal patients treated with long-term adjuvant tamoxifen show a 3-4-fold increase in the risk of developing endometrial cancer. Consequently, a new second line agent should be more antiestrogenic and less estrogen-like on the uterus, and be effective at controlling the growth of breast cancer after exposure to tamoxifen. The purpose was to evaluate the effects of the new tamoxifen analogue GW5638 on breast and endometrial cancer growth. EXPERIMENTAL DESIGN: Athymic mice were transplanted with an endometrial tumor model (ECC-1 E2) that is responsive to estrogen and has never been exposed to antiestrogen. In addition, we used three breast tumor models: a tamoxifen-na?ve tumor (T47D-E2) and two tamoxifen-stimulated tumors (MT2 TAM and MCF-7 TAM LT). The antiestrogen GW5638 (1.5 mg daily), tamoxifen (0.5 mg or 1.5 mg daily), and raloxifene (1.5 mg daily) were given p.o. The pure antiestrogen ICI182,780 (5 mg once a week) was given s.c. Western blots from MCF-7 TAM breast tumors were performed to demonstrate the regulation of estrogen receptor alpha expression by different ligands. RESULTS: Estradiol and GW5638 down-regulated the receptor compared with control. ICI182,780 completely degraded the receptor but tamoxifen had no effect. GW5638 did not promote tumor growth, and was effective in blocking the effects of postmenopausal estradiol on the growth of tamoxifen-na?ve breast and endometrial tumors. However, raloxifene did not completely block the effects of postmenopausal estradiol on the growth of tamoxifen-na?ve endometrial tumor after 14 weeks. GW5638 and ICI182,780 but not raloxifene were also effective in blocking the tamoxifen-stimulated breast tumor growth in athymic mice. CONCLUSIONS: GW5638 is more effective than raloxifene in blocking the effect of estrogen on tamoxifen-na?ve endometrial cancer. More importantly, GW5638, like the pure antiestrogen ICI182,780, is able to block the growth of breast cancer stimulated by tamoxifen differently from raloxifene. GW5638 down-regulates estrogen receptor but does not completely destroy the receptor. Therefore, based on our findings, GW5638 could be developed as a second line agent for advanced breast cancer patients and an important first line agent to evaluate as an adjuvant treatment or chemopreventive.