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Biomedical subjects

W Franks

Publications and source records attributed to W Franks.

18 recordsLinked to original sources

Single-chip microelectronic system to interface with living cells.

A high degree of connectivity and the coordinated electrical activity of neural cells or networks are believed to be the reason that the brain is capable of highly sophisticated information processing. Likewise, the effectiveness of an animal heart largely depends on such coordinated cell activity. To advance our understanding of these complex biological systems, high spatiotemporal-resolution techniques to monitor the cell electrical activity and an ideally seamless interaction between cells and recording devices are desired. Here we present a monolithic microsystem in complementary metal oxide semiconductor (CMOS) technology that provides bidirectional communication (stimulation and recording) between standard electronics technology and cultured electrogenic cells. The microchip can be directly used as a substrate for cell culturing, it features circuitry units per electrode for stimulation and immediate cell signal treatment, and it provides on-chip signal transformation as well as a digital interface so that a very fast, almost real-time interaction (2 ms loop time from event recognition to, e.g., a defined stimulation) is possible at remarkable signal quality. The corresponding spontaneous and stimulated electrical activity recordings with neuronal and cardiac cell cultures will be presented. The system can be used to, e.g., study the development of neural networks, reveal the effects of neuronal plasticity and study cellular or network activity in response to pharmacological treatments.

Action Potentials↗

Patterned cell adhesion by self-assembled structures for use with a CMOS cell-based biosensor.

A strategy for patterned cell adhesion based on chemical surface modification is presented. To confine cell adhesion to specific locations, an engineered surface for high-contrast protein adsorption and, hence, cell attachment has been developed. Surface functionalization is based on selective molecular-assembly patterning (SMAP). An amine-terminated self-assembled monolayer is used to define areas of cell adhesion. A protein-repellent grafted copolymer, poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG), is used to render the surrounding silicon dioxide resistant to protein adsorption. X-ray photoelectron spectroscopy, scanning ellipsometry and fluorescence microscopy techniques were used to monitor the individual steps of the patterning process. Successful guided growth using these layers is demonstrated with primary neonatal rat cardiomyocytes, up to 4 days in vitro, and with the HL-1 cardiomyocyte cell line, up to 7 days in vitro. The advantage of the presented method is that high-resolution engineered surfaces can be realized using a simple, cost-effective, dip-and-rinse process. The technique has been developed for application on a CMOS cell-based biosensor, which comprises an array of microelectrodes to extracellularly record electrical activity from cardiomyocytes.

Animals↗

CMOS microelectrode array for the monitoring of electrogenic cells.

Signal degradation and an array size dictated by the number of available interconnects are the two main limitations inherent to standalone microelectrode arrays (MEAs). A new biochip consisting of an array of microelectrodes with fully-integrated analog and digital circuitry realized in an industrial CMOS process addresses these issues. The device is capable of on-chip signal filtering for improved signal-to-noise ratio (SNR), on-chip analog and digital conversion, and multiplexing, thereby facilitating simultaneous stimulation and recording of electrogenic cell activity. The designed electrode pitch of 250 microm significantly limits the space available for circuitry: a repeated unit of circuitry associated with each electrode comprises a stimulation buffer and a bandpass filter for readout. The bandpass filter has corner frequencies of 100 Hz and 50 kHz, and a gain of 1000. Stimulation voltages are generated from an 8-bit digital signal and converted to an analog signal at a frequency of 120 kHz. Functionality of the read-out circuitry is demonstrated by the measurement of cardiomyocyte activity. The microelectrode is realized in a shifted design for flexibility and biocompatibility. Several microelectrode materials (platinum, platinum black and titanium nitride) have been electrically characterized. An equivalent circuit model, where each parameter represents a macroscopic physical quantity contributing to the interface impedance, has been successfully fitted to experimental results.

Action Potentials↗

Long term outcome of secondary glaucoma following vitreoretinal surgery.

PURPOSE: To determine the long term outcome of secondary glaucoma following retinal reattachment surgery. METHOD: A longitudinal retrospective study was undertaken of the medical records of patients referred to the Glaucoma Service at Moorfields Eye Hospital following retinal reattachment surgery. The main outcome measures were final intraocular pressure (IOP), progression in cup:disc ratio, and final visual acuity outcome. RESULTS: A total of 70 eyes of 70 patients (41 males and 29 females) were identified and included in the analysis. Mean increase of IOP 2-3 weeks following the first vitreoretinal procedure was 6 (SD 3) mm Hg. After a mean follow up of approximately 4 years the mean IOP had significantly decreased from 33 (SD 10) to 16 (SD 8) mm Hg (p<0.001). The visual outcome of eyes with final IOP less than 6 or greater than 21 mm Hg was significantly worse compared with those eyes with a normal (6-21 mm Hg) range of pressure (p = 0.022 and p = 0.009 respectively). Despite the effective control of IOP in the majority of patients during the follow up period, there was mild progression of the mean vertical cup:disc ratio from 0.6 (SD 0.2) to 0.7 (SD 0.2) (p<0.001). CONCLUSION: Secondary glaucoma is a major complication following retinal reattachment surgery. Medical treatment is successful in lowering IOP in most patients. In persisting cases surgical treatment is very effective, however it can be associated with an increased risk of postoperative hypotony. Despite apparently adequate IOP control there may be progressive cupping of the optic disc.

Adult↗

Ascorbic acid dynamics in the seriously ill and injured.

BACKGROUND: In addition to the known beneficial effects of ascorbic acid on wound healing and the immune response, it is also a potent extracellular antioxidant. Recent work in septic rats suggests that high-dose ascorbic acid total parenteral nutrition (TPN) supplementation may protect cells from free radical injury and improve survival. In this study, we determined ascorbic acid levels in the immediate post-injury/illness period and evaluated the ability of early short-term high levels of ascorbic acid in TPN to normalize plasma levels. MATERIALS AND METHODS: Ascorbic acid levels were determined in 12 critically injured patients and 2 patients with severe surgical infections. Each patient received TPN supplemented with increasing doses of ascorbic acid over a 6-day period. Therapeutic responses were determined by plasma and urine measurements using high-pressure liquid chromatography. RESULTS: The initial mean +/- SEM baseline plasma ascorbic acid concentration was depressed (0.11 +/- 0.03 mg/dl) and unresponsive following 2 days on 300 mg/day supplementation (0.14 +/- 0.03; P = 1.0) and only approached low normal plasma levels following 2 days on 1000 mg/day (0.32 +/- 0.08; P = 0.36). A significant increase was noted following 2 days on 3000 mg/day (1.2 +/- 0.03; P = 0.005). CONCLUSION: We confirmed extremely low plasma levels of ascorbic acid following trauma and infection. Maximal early repletion of this vitamin requires rapid pool filling early in the post-injury period using supraphysiologic doses for 3 or more days.

Adult↗

Peribulbar anaesthesia for cataract surgery: prilocaine versus lignocaine and bupivacaine.

PURPOSE: Prilocaine has recently been introduced for use in ocular local anaesthesia. A prospective randomised double-masked study was undertaken to assess the efficacy of prilocaine 2% plain versus a mixture of lignocaine 1% and bupivacaine 0.5%, each with hyaluronidase. METHODS: Seventy-five patients were recruited. Local anaesthetic was given by a two-injection transconjunctival peribulbar technique. Injection and perioperative pain were graded by visual analogue pain score (range 0-10). Akinesia and orbicularis function were graded by the surgeon. RESULTS: The two anaesthetic mixtures were comparable in efficacy in producing anaesthesia and akinesia. Using the Mann-Whitney U-test for significance, pain of injection ranked as a mean of 0.88 for prilocaine and 1.03 for lignocaine and bupivacaine (p = 0.48, U = 635.5) Perioperative pain was ranked as a mean of 1.17 for prilocaine and 0.91 for lignocaine and bupivacaine (p = 0.41, U = 629.0). CONCLUSIONS: Prilocaine is a useful alternative anaesthetic agent for eye surgery that has low toxicity and is effective without adrenaline.

Anesthetics, Local↗

Technetium-99m-HMPAO SPECT, CT and MRI in the evaluation of patients with chronic traumatic brain injury: a correlation with neuropsychological performance.

UNLABELLED: The purposes of this study were: (1) to compare 99mTc-hexamethylpropyleneamineoxime (HMPAO) SPECT with CT and MRI in chronic traumatic brain injury (TBI) patients and (2) to correlate both functional and structural neuroimaging measurements of brain damage with neuropsychological (NP) performance. METHODS: Twenty-nine patients (minor TBI, n = 15 and major TBI, n = 14) and 17 normal controls (NC) underwent HMPAO SPECT, CT, MRI and NP testing. Imaging data were analyzed both visually and quantitatively. RESULTS: Nineteen (66%) patients showed 42 abnormalities on SPECT images, whereas 13 (45%) and 10 (34%) patients showed 29 abnormalities on MRI and 24 abnormalities on CT. SPECT detected relatively more abnormalities than CT or MRI in the minor TBI subgroup. The TBI group showed impairment on 11 tests for memory, attention and executive function. Of these, the anterior-posterior ratio (APR) correlated with six tests, whereas the ventricle-to-brain ratio (VBR), a known structural index of a poor NP outcome, correlated with only two tests. CONCLUSION: In evaluating chronic TBI patients, HMPAO SPECT, as a complement to CT or MRI, may play a useful role by demonstrating brain dysfunction in morphologically intact brain regions and providing objective evidence for some of the impaired NP performance.

Adult↗

The treatment of bullous rhegmatogenous retinal detachment.

We describe the results of a consecutive series of 97 cases of bullous superior retinal detachment treated by conventional surgery. The retinal detachments were characterized by either a single retinal break or multiple retinal breaks confined within 1 clock hour and no proliferative vitreoretinopathy. The surgery involved sequential drainage of subretinal fluid, injection of air, cryotherapy and the application of local explant. All cases would otherwise be suitable for pneumatic retinopexy. The anatomical success rate was 85.5% with a single operation and 97% with further procedures. We report on the complications encountered and appraise the advantages and disadvantages of this operation. Forty-five of the 97 cases had detachment of the macula for less than 2 weeks, and 35 of the 45 (80%) achieved a visual acuity of 6/18 or better. These visual results challenge the assertion that better visual outcome might be attained with pneumatic retinopexy.

Air↗

Hypertropia following insertion of inferiorly sited double-plate Molteno tubes.

The use of double-plate Molteno tubes is well established in the management of intractable glaucoma, particularly in eyes that may have had previous surgical procedures, often involving the superior conjunctiva with subsequent subconjunctival scarring. As it is frequently the case that the area of least scarring is inferiorly, we have sited the tubes there but have found that, although this usually provides good control of intraocular pressure, successful drainage of aqueous has been associated with the development of hypertropia due to upward displacement of the globe by fluid encapsulated around the plates. We report a retrospective study of 16 eyes undergoing inferiorly sited double-plate Molteno tubes, in which 9 eyes developed significant hypertropia at a mean time after insertion of 3.5 months. Mean degree of hypertropia was 9.8 prism dioptres. The management of this complication is discussed.

Adolescent↗

Technetium-99m-HMPAO SPECT in the evaluation of patients with a remote history of traumatic brain injury: a comparison with x-ray computed tomography.

The functional imaging modality has potential for demonstrating parenchymal abnormalities not detectable by traditional morphological imaging. Fifty-three patients with a remote history of traumatic brain injury (TBI) were studied with SPECT using 99mTc-hexamethylpropyleneamineoxime (HMPAO) and x-ray computed tomography (CT). Overall, 42 patients (80%) showed regional cerebral blood flow (rCBF) deficits by HMPAO SPECT, whereas 29 patients (55%) showed morphological abnormalities by CT. Out of 20 patients with minor head injury, 12 patients (60%) showed rCBF deficits and 5 patients (25%) showed CT abnormalities. Of 33 patients with major head injury, 30 patients (90%) showed rCBF deficits and 24 patients (72%) showed CT abnormalities. Thus, HMPAO SPECT was more sensitive than CT in detecting abnormalities in patients with a history of TBI, particularly in the minor head injury group. In the major head injury group, three patients showed localized cortical atrophy by CT and normal rCBF by HMPAO SPECT. In the evaluation of TBI patients, HMPAO SPECT is a useful technique to demonstrate regional brain dysfunction in the presence of morphological integrity as assessed by CT.

Adult↗

Serous retinal detachment following glaucoma filtering surgery.

We report the occurrence of serous retinal detachment in association with choroidal effusion and hypotony in six eyes that had undergone glaucoma filtering surgery. Hypotony with choroidal effusion was documented in five patients before the onset of serous retinal detachment. While one patient underwent vitrectomy, treatment was conservative in the other patients. Serous retinal detachment and choroidal effusions resolved spontaneously as the intraocular pressure normalized. Although one patient regained preoperative visual acuity, all other patients lost at least one line of Snellen acuity.

Adolescent↗