The impact of PSA testing frequency on prostate cancer incidence and treatment in older men.

To quantify the downstream impact of PSA testing on cancer characteristics and utilization of cancer therapies among men aged 70 or older, we utilized patients diagnosed with prostate cancer in 2004-2005 in the Surveillance, Epidemiology and End Results (SEER)-Medicare and their Medicare claims before their cancer diagnosis during 2000-2005. Among men in the highest testing group (4-6 PSA tests), 75% were diagnosed with low- or intermediate-risk of disease, but 77% received treatments within 180 days of cancer diagnosis. More than 45% of newly diagnosed patients in 2004-2005 had 4-6 PSA tests before their cancer diagnosis during 2000-2005. Men in the high testing group were 3.57 times more likely to receive cancer treatments (either surgery, radiation or hormonal therapy) when compared with men who had no previous PSA testing during the same time period. Among men aged 75+ diagnosed with low-risk cancer, men in the high testing group were 78% more likely to receive treatment than those who had no previous PSA testing. In conclusion, given the lack of evidence of effective treatment for elderly patients diagnosed with low- and intermediate-risk prostate cancer and our inability to distinguish indolent from aggressive cancer, more frequent PSA testing among elderly population may exacerbate the risk of overdiagnosis and overtreatment.

Treatment profile and complications associated with cryotherapy for localized prostate cancer: a population-based study.

The aim of this study was to assess the treatment patterns and 3-12-month complication rates associated with receiving prostate cryotherapy in a population-based study. Men >65 years diagnosed with incident localized prostate cancer in Surveillance Epidemiology End Results (SEER)-Medicare-linked database from 2004 to 2005 were identified. A total of 21,344 men were included in the study, of which 380 were treated initially with cryotherapy. Recipients of cryotherapy versus aggressive forms of prostate therapy (ie, radical prostatectomy or radiation therapy) were more likely to be older, have one co-morbidity, low income, live in the South and be diagnosed with indolent cancer. Complication rates increased from 3 to 12 months following cryotherapy. By the twelfth month, the rates for urinary incontinence, lower urinary tract obstruction, erectile dysfunction and bowel bleeding reached 9.8, 28.7, 20.1 and 3.3%, respectively. Diagnoses of hydronephrosis, urinary fistula or bowel fistula were not evident. The rates of corrective invasive procedures for lower urinary tract obstruction and erectile dysfunction were both <2.9% by the twelfth month. Overall, complications post-cryotherapy were modest; however, diagnoses for lower urinary tract obstruction and erectile dysfunction were common.

Size-selective fractionation of nanoparticles at an application scale using CO2 gas-expanded liquids.

Size-based fractionation of nanoparticles remains a non-trivial task for the preparation of well-defined nanomaterials for certain applications and fundamental studies. Typical fractionation techniques prove to be inefficient for large nanoparticle quantities due to several factors including the expense of equipment, throughput constraints, and the amount of organic solvent waste produced. Through the use of the pressure-tunable physico-chemical properties of CO2-expanded liquids, a rapid, precise, and environmentally sustainable size-selective fractionation of ligand-stabilized nanoparticles is possible through simple variations in applied CO2 pressure. An apparatus capable of fractionating large quantities of nanoparticles into distinct fractions with the ability to control mean diameters and size distributions has been developed. This apparatus consists of three vertically mounted pressure vessels connected in series with needle valves. This process, at current design scales, operated at room temperature, and CO2 pressures between 0 and 50 bar, results in a batch size-selective fractionation of a concentrated nanoparticle dispersion. This paper presents this new apparatus and the separation results of various single pass fractionations as well as recursive fractionations.

A gas-expanded liquid nanoparticle deposition technique for reducing the adhesion of silicon microstructures.

A gas-expanded liquid-based nanoparticle deposition technique was integrated with a critical point drying process to modify the surface of polysilicon microstructures in order to reduce the adhesion that ordinarily occurs due to dominant interfacial surface forces. Dodecanethiol-capped gold nanoparticles (AuNPs) were deposited onto arrays of cantilever beams using gas-expanded liquid technology in an effort to increase the surface roughness, thereby reducing the real contact surface area as well as changing the chemical constituents of the contacting areas. Both AuNP-coated and uncoated (native oxide surface) arrays were actuated electrostatically in order to determine the work of adhesion. The results of this study indicate that while cantilever beams with only their native oxide exhibit apparent adhesion energies of about 700 +/- 100 microJ m(-2), cantilever beam arrays coated with AuNPs exhibit an apparent adhesion energy of about 8 microJ m(-2) or less. These results indicate that metallic nanoparticle coatings can be successfully applied to micromachines and provide a drastic reduction in apparent adhesion energy.

Dendrites determine the contribution of after depolarization potentials (ADPs) to generation of repetitive action potentials in hypothalamic gonadotropin releasing-hormone (GnRH) neurons.

The impact of structure in modulating synaptic signals originating in dendrites is widely recognized. In this study, we focused on the impact of dendrite morphology on a local spike generating mechanism which has been implicated in hormone secretion, the after depolarization potential (ADP). Using multi-compartmental models of hypothalamic GnRH neurons, we systematically truncated dendrite length and determined the consequence on ADP amplitude and repetitive firing. Decreasing the length of the dendrite significantly increased the amplitude of the ADP and increased repetitive firing. These effects were observed in dendrites both with and without active conductances suggesting they largely reflect passive characteristics of the dendrite. In order to test the findings of the model, we performed whole-cell recordings in GnRH neurons and elicited ADPs using current injection. During recordings, neurons were filled with biocytin so that we could determine dendritic and total projection (dendrite plus axon) length. Neurons exhibited ADPs and increasing ADP amplitude was associated with decreasing dendrite length, in keeping with the predictions of the models. Thus, despite the relatively simple morphology of the GnRH neuron's dendrite, it can still exert a substantial impact on the final neuronal output.

Synaptic integration in hypothalamic gonadotropin releasing hormone (GnRH) neurons.

The impact of the A-type GABA (GABA-A) receptor in gonadotropin releasing hormone (GnRH) neurons is controversial. In adult GnRH neurons, the GABA-A receptor conductance has been reported to either hyperpolarize or depolarize GnRH neurons. Regardless of whether GABA is inhibitory or excitatory in GnRH neurons, GABAergic input would be integrated with post-synaptic potentials generated by other synaptic inputs. We used dynamic current clamping and compartmental computer modeling to examine the integration of AMPA-type glutamatergic input and GABA-mediated input in both the hyperpolarizing (inhibitory) and depolarizing (excitatory) modes in GnRH neurons from transgenic mice (Mus Musculus) generated on a C57BL6 background. In both living and model neurons, action potentials were most likely a few ms after a maximum in AMPA conductance coincided with a minimum in inhibitory GABA. Excitatory GABA interacted differently with AMPA, with spikes most likely, in both dynamic clamping of living neurons and in model neurons, when a maximum in AMPA coincided with the decay from peak of a maximum in GABA. Distributing synapses along the dendrite maximized the temporal relationship between AMPA and GABA conductances and therefore, the potential for spiking. Thus, these two dominant neurotransmitters could interact in multiple frames to generate action potentials in GnRH neurons.

Dendritic processing of excitatory synaptic input in hypothalamic gonadotropin releasing-hormone neurons.

The activity of hypothalamic GnRH neurons results in the intermittent release of GnRH required for reproductive function. This intermittent neurosecretory activity has been proposed to reflect integration of intrinsic properties of and synaptic input to GnRH neurons. Determining the relative impact of synaptic inputs at different locations on the GnRH neuron is difficult, if not impossible, using only experimental approaches. Thus, we used electrophysiological recordings and neuronal reconstructions to generate computer models of GnRH neurons to examine the effects of synaptic inputs at varying distances from the soma along dendrites. The parameters of the models were adjusted to duplicate measured passive and active electrophysiology of cells from mouse brain slices. Our morphological findings reinforce the emerging picture of a complex dendritic structure of GnRH neurons. Furthermore, analysis of reduced morphology models indicated that this population of cells is unlikely to exhibit low-frequency tonic spiking in the absence of synaptic input. Finally, applying realistic patterns of synaptic input to modeled GnRH neurons indicates that synapses located more than about 30% of the average dendrite length from the soma cannot drive firing at frequencies consistent with neuropeptide release. Thus, processing of synaptic input to dendrites of GnRH neurons is probably more complex than simple summation.

T594M mutation of the epithelial sodium channel beta-subunit gene in pre-eclampsia and eclampsia in Black South African women.

The possible role of the beta-subunit of the epithelial sodium channel T594M polymorphism in hypertensive disorders of pregnancy has not been examined. This study compared Black South African women with pre-eclampsia (n= 204), early onset pre-eclampsia (n= 67), eclampsia (n= 120) and gestational hypertension (n= 78) with 338 women from the same ethnic group who had full-term normotensive pregnancies, for the presence of the T594M polymorphism. The variant allele was detected in 1.7% to 3.8% of the various patient groups and in 3.6% of the control group reflecting no significant difference. These results suggest that the T594M polymorphism in the sodium channel beta-subunit is not associated with the pathogenesis of pre-eclampsia or gestational hypertension.