Seeing single atoms.

New discoveries and ideas often occur at the confluence of events and technologies that allow them to happen. So it was with the first electron microscopic observations of individual atoms at the University of Chicago laboratory of Albert Crewe forty years ago. This paper will describe the technologies developed then, present some of the historical instrumental details and describe the rationale for the designs that came about in that laboratory over a period of about a decade.

Bilateral renal malakoplakia with acute renal failure: a case report and literature review.

Malakoplakia involving the genitourinary tract is a rare inflammatory disorder that presents a diagnostic challenge. Renal parenchymal involvement is particularly uncommon. We report a case of bilateral renal malakoplakia that presented with acute renal failure and simulated xanthogranulomatous pyelonephritis (XGP). The etiology, clinical course, and management of malakoplakia are reviewed, emphasizing the distinct characteristics of the disease that lead to its accurate diagnosis.

Current cystoscopy practice of recent graduates of obstetrics and gynecology residency: a survey study.

OBJECTIVE: To provide data regarding the training, credentialing and use of cystoscopy among recent obstetrics and gynecology (Ob/Gyn) residents. STUDY DESIGN: A total of 98 surveys were sent to recent graduates of Ob/Gyn residency programs in the District of Columbia (DC). Questions concerning cystoscopy in residency training, current cystoscopy privileges and utilization of this technique were asked. RESULTS: Of the 98 surveys sent, 34 (35%) were completed. Of the survey respondents 88% reported rotating through a urogynecology or female urology service during residency, and the majority of residents spent at least 2 months on service. A total of 68% of survey respondents reported currently having cystoscopy privileges. Only 12% of those surveyed reported performing routine cystoscopy after hysterectomy. When asked why, most participants reported performing cystoscopy only if urinary tract injury is suspected. CONCLUSION: The majority of recent graduates of Ob/Gyn residency training programs surveyed in DC are exposed to and receive privileges for cystoscopy. However, few choose to use it after routine hysterectomy. Given the fact that 75% of urinary tract injuries occur during gynecologic surgery and that these injuries are more likely to occur at the hands of newly minted surgeons, a change in this practice may be warranted.

Flexible multielectrodes can resolve multiple muscles in an insect appendage.

Research into the neuromechanical basis of behavior, either in biomechanics, neuroethology, or neuroscience, is frequently limited by methods of data collection. Two of the most pressing needs are for methods with which to (1) record from multiple neurons or muscles simultaneously and (2) perform this recording in intact, behaving animals. In this paper we present the fabrication and testing of flexible multielectrode arrays (fMEAs) that move us significantly towards these goals. The fMEAs were used to record the activity of several distinct units in the coxa of the cockroach Blaberus discoidalis. The devices fabricated here address the first goal in two ways: (1) their flexibility allows them to be inserted into an animal and guided through internal tissues in order to access distinct groups of neurons and muscles and (2) their recording site geometry has been tuned to suit the anatomy under study, yielding multichannel spike waveforms that are easily separable under conditions of spike overlap. The flexible nature of the devices simultaneously addresses the second goal, in that it is less likely to interfere with the natural movement of the animal.

On-chip micro-biosensor for the detection of human CD4(+) cells based on AC impedance and optical analysis.

The current study was undertaken to fabricate a small micro-electrode on-chip to rapidly detect and quantify human CD4(+) cells in a minimal volume of blood through impedance measurements made with simple electronics that could be battery operated implemented in a hand held device. The micro-electrode surface was non-covalently modified sequentially by incubation with solutions of protein G', human albumin, monoclonal mouse anti-human CD4, and mouse IgG. The anti-human CD4 antibody served as the recognition and capture molecule for CD4(+) cells present in human blood. The binding of these biomolecules to the micro-electrodes was verified by impedance and cyclic voltammetry measurements. An increase in impedance was detected for each layer of protein adsorbed onto the micro-electrode surface. This process was shown to be highly repeatable. Increased impedance was measured when CD4(+) cells were captured on the micro-electrode, and the impedance also increased as the number of captured cells increased. Fluorescence microscopy of captured cells immunolabeled with anti-human CD4, CD8, and CD19 antibodies, and the nuclear label DAPI, confirmed that only CD4(+) cells were captured. The results were highly dependent on the specimen preparation method used. We conclude that the on-chip capture system can efficiently quantify the number of CD4(+) cells.

Model neural prostheses with integrated microfluidics: a potential intervention strategy for controlling reactive cell and tissue responses.

Model silicon intracortical probes with microfluidic channels were fabricated and tested to examine the feasibility of using diffusion-mediated delivery to deliver therapeutic agents into the volume of tissue exhibiting reactive responses to implanted devices. Three-dimensional probe structures with microfluidic channels were fabricated using surface micromachining and deep reactive ion etching (DRIE) techniques. In vitro functional tests of devices were performed using fluorescence microscopy to record the transient release of Texas Red labeled transferrin (TR-transferrin) and dextran (TR-dextran) from the microchannels into 1% w/v agarose gel. In vivo performance was characterized by inserting devices loaded with TR-transferrin into the premotor cortex of adult male rats. Brain sections were imaged using confocal microscopy. Diffusion of TR-transferrin into the extracellular space and uptake by cells up to 400 microm from the implantation site was observed in brain slices taken 1 h postinsertion. The reactive tissue volume, as indicated by the presence of phosphorylated mitogen-activated protein kinases (MAPKs), was characterized using immunohistochemistry and confocal microscopy. The reactive tissue volume extended 600, 800, and 400 microm radially from the implantation site at 1 h, 24 h, and 6 weeks following insertion, respectively. These results indicate that diffusion-mediated delivery can be part of an effective intervention strategy for the treatment of reactive tissue responses around chronically implanted intracortical probes.

Extracellular recordings from patterned neuronal networks using planar microelectrode arrays.

Neuronal cell networks have been reconstructed on planar microelectrode arrays (MEAs) from dissociated hippocampal pyramidal neurons. Microcontact printing (microCP) and a photoresist-liftoff method were used to selectively localize poly-L-lysine (PLL) on the surface of MEAs. Haptotaxis led to the organization of the neurons into networks localized adjacent to microelectrodes. Various grids of PLL with 2-25-microm-wide lines spaced by 50-200 microm with 15-25-microm nodes at intersection points were used to guide cell body attachment and neurite outgrowth. Bursting activity with spike amplitude attenuation was observed, and multichannel recordings detected instances of coincident firing activity. Finally, we present here an extracellular recording from a approximately 2 microm bundle of guided neurites.

Controlling cellular reactive responses around neural prosthetic devices using peripheral and local intervention strategies.

While chronic use of indwelling micromachined neural prosthetic devices has great potential, the development of reactive responses around them results in a decrease in electrode function over time. Since the cellular events responsible for these responses may be anti-inflammatory in nature, we have tested the effectiveness of dexamethasone and cyclosporin A as potential drugs for developing intervention strategies following insertion of single-shank micromachined silicon devices. Peripheral injection of dexamethasone was effective in attenuating increased expression of glial fibrillary acidic protein and astrocyte hyperplasia observed during both initial- and sustained-reactive responses observed at one and six weeks post insertion, respectively. Peripheral injection of cyclosporin A had no positive effect. If anything, application of this drug increased the early reactive response. Effectiveness of local release of dexamethasone in rat neocortex was tested by inserting ribbons of poly (ethyl-vinyl) acetate containing 35% (w/w) dexamethasone. Initial concentrations of dexamethasone were similar to those obtained by peripheral injection. Local drug release provided continued control of cellular reactive responses during the six-week study period. These results demonstrate that peripheral delivery of dexamethasone can be used to control reactive responses and that local drug delivery by slow-release from biocompatible polymers may be a more effective method of drug intervention. Incorporating these strategies on micromachined devices may provide an intervention strategy that will insure the chronic functioning of electrodes on intracortical neuroprosthetic devices.