Oxygen supply by photosynthesis to an implantable islet cell device.

Transplantation of islet cells is an effective treatment for type 1 diabetes with critically labile metabolic control. However, during islet isolation, blood supply is disrupted, and the transport of nutrients/metabolites to and from the islet cells occurs entirely by diffusion. Adequate oxygen supply is essential for function/survival of islet cells and is the limiting factor for graft integrity. Recently, we developed an immunoisolated chamber system for transplantation of human islets without immunosuppression. This system depended on daily oxygen supply. To provide independence from this external source, we incorporated a novel approach based on photosynthetically-generated oxygen. The chamber system was packed sandwich-like with a slab of immobilized photosynthetically active microorganisms (Synechococcus lividus) on top of a flat light source (LEDs, red light at 660 nm, intensity of 8 µE/m(2)/s). Islet cells immobilized in an alginate slab (500-1,000 islet equivalents/cm(2)) were mounted on the photosynthetic slab separated by a gas permeable silicone rubber-Teflon membrane, and the complete module was sealed with a microporous polytetrafluorethylene (Teflon) membrane (pore size: 0.4 µm) to protect the contents from the host immune cells. Upon illumination, oxygen produced by photosynthesis diffused via the silicone Teflon membrane into the islet compartment. Oxygen production from implanted encapsulated microorganisms was stable for 1 month. After implantation of the device into diabetic rats, normoglycemia was achieved for 1 week. Upon retrieval of the device, blood glucose levels returned to the diabetic state. Our results demonstrate that an implanted photosynthetic bioreactor can supply oxygen to transplanted islets and thus maintain islet viability/functionality.

Effect of epilepsy magnetic source imaging on intracranial electrode placement.

OBJECTIVE: Intracranial electroencephalography (ICEEG) with chronically implanted electrodes is a costly invasive diagnostic procedure that remains necessary for a large proportion of patients who undergo evaluation for epilepsy surgery. This study was designed to evaluate whether magnetic source imaging (MSI), a noninvasive test based on magnetoencephalography source localization, can supplement ICEEG by affecting electrode placement to improve sampling of the seizure onset zone(s). METHODS: Of 298 consecutive epilepsy surgery candidates (between 2001 and 2006), 160 patients were prospectively enrolled by insufficient localization from seizure monitoring and magnetic resonance imaging results. Before presenting MSI results, decisions were made whether to proceed with ICEEG, and if so, where to place electrodes such that the hypothetical seizure-onset zone would be sampled. MSI results were then provided with allowance of changes to the original plan. RESULTS: MSI indicated additional electrode coverage in 18 of 77 (23%) ICEEG cases. In 39% (95% confidence interval, 16.4-61.4), seizure-onset ICEEG patterns involved the additional electrodes indicated by MSI. Sixty-two patients underwent surgical resection based on ICEEG recording of seizures. Highly localized MSI was significantly associated with seizure-free outcome (mean, 3.4 years; minimum, >1 year) for the entire surgical population (n = 62). INTERPRETATION: MSI spike localization increases the chance that the seizure-onset zone is sampled when patients undergo ICEEG for presurgical epilepsy evaluations. The clinical impact of this effect, improving diagnostic yield of ICEEG, should be considered in surgery candidates who do not have satisfactory indication of epilepsy localization from seizure semiology, electroencephalogram, and magnetic resonance imaging.

A novel device for islet transplantation providing immune protection and oxygen supply.

Islet transplantation as a biological ß-cell replacement therapy has emerged as a promising option for achieving restoration of metabolic control in type 1 diabetes patients. However, partial or complete loss of islet graft function occurs in relatively short time (months to few years) after implantation. The high rate of early transplant dysfunction has been attributed to poorly viable and/or functional islets and is mediated by innate inflammatory response at the intravascular (hepatic) transplant site and critical lack of initial nutrient/oxygen supply prior to islet engraftment. In addition, the diabetogenic effect of mandatory immunosuppressive agents, limited control of alloimmunity, and the recurrence of autoimmunity limit the long-term success of islet transplantation. In order to abrogate instant blood-mediated inflammatory reaction and to provide oxygen supply for the islet graft, we have developed an extravascular (subcutaneous) transplant macrochamber (the 'ßAir' device). This device contains islets immobilized in alginate, protected from the immune system by a thin hydrophilized teflon membrane impregnated with alginate and supplied with oxygen by daily refueling with oxygen-CO (2) mixture. We have demonstrated successful utilization of the oxygen-refueling macrochamber for sustained islet viability and function as well as immunoprotection after allogeneic subcutaneous transplantation in healthy minipigs. Considering the current limitations of intraportal islet engraftment and the restricted indication for islet transplantation mainly due to necessary immunosuppressive therapy, this work could very likely lead to remarkable improvements in the procedure and moreover opens up further strategies for porcine islet cell xenotransplantation.

Functional imaging: II. Prediction of epilepsy surgery outcome.

OBJECTIVE: To gain information on the value of magnetic source imaging (MSI), 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and ictal single photon emission computed tomography (SPECT) to predict seizure-free outcome following epilepsy surgery in patients who require intracranial electroencephalography (ICEEG). METHODS: This work was part of a prospective observation study of epilepsy surgery candidates not sufficiently localized with scalp EEG and MRI. Of 160 patients enrolled 62 completed ICEEG and subsequent surgical resection. Sixty-one percent resulted in an Engel I seizure-free outcome at a minimum of one-year follow-up (mean = 3.4 years). Sensitivity, specificity, and predictive values were computed for each modality. Multivariate logistical regression was used to identify prediction of surgical outcome by imaging test. RESULTS: MSI sensitivity for a conclusively localized study was 55% with a positive predictive value of 78%. Eliminating non-diagnostic MSI cases (no spikes captured during recording) yielded a corrected negative predictive value of 64%. With available comparison subgroups FDG-PET and ictal SPECT values were similar to MSI. The OR (adjusted for epilepsy and MRI classification) for MSI prediction of seizure-free outcome was 4.4 (p =0.01). In cases with both PET and MSI, the adjusted OR for PET was 7.1 (p <0.01) and for MSI was 6.4 (p = 0.01). In the cases with all three tests (n = 27), ictal SPECT had the highest OR of 9.1 (p = 0.05). INTERPRETATION: MSI, FDG-PET, and ictal SPECT each have clinical value in predicting seizure-free surgical outcome in epilepsy surgery candidates who typically require ICEEG.

Functional imaging: I. Relative predictive value of intracranial electroencephalography.

OBJECTIVE: To gain information on the predictive and prognostic value of magnetic source imaging (MSI), 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET), and ictal single-photon emission computed tomography (SPECT) as compared with intracranial electroencephalography (ICEEG) localization in epilepsy surgery. METHODS: This work was part of a cohort study of epilepsy surgery candidates not sufficiently localized with noninvasive studies. Of 160 patients enrolled over 4 years, 77 completed ICEEG seizure monitoring. Sensitivity, specificity, and predictive values relative to ICEEG were computed for each modality. RESULTS: Seizures were not captured in five patients. Of the 72 diagnostic ICEEG studies, seizure localization results were 74% localized, 10% multifocal, and 17% nonlocalized. Sixty-one percent were localized to neocortical regions. Depending on patient subgroup pairs, sensitivity ranged from 58 to 64% (MSI), 22 to 40% (PET), and 39 to 48% (SPECT); specificity ranges were 79 to 88% (MSI), 53 to 63% (PET), and 44 to 50% (SPECT). Gains in diagnostic yield were seen only with the combination of MSI and PET or MSI and ictal SPECT. Localization concordance with ICEEG was greatest with MSI, but a significant difference was demonstrated only between MSI and PET. Moderate redundancy was seen between PET and ictal SPECT (kappa = 0.452; p = 0.011). INTERPRETATION: Conclusively positive MSI has a high predictive value for seizures localized with ICEEG. Diagnostic gain may be achieved with addition of either PET or ictal SPECT to MSI. Diagnostic values for imaging tests are lower than "true values" because of the limitations of ICEEG as a gold standard.

Overcoming resolution limits with quantum sensing.

The field of quantum sensing explores the use of quantum phenomena to measure a broad range of physical quantities, of both static and time-dependent types. While for static signals the main figure of merit is sensitivity, for time dependent signals it is spectral resolution, i.e. the ability to resolve two different frequencies. Here we study this problem, and develop new superresolution methods that rely on quantum features. We first formulate a general criterion for superresolution in quantum problems. Inspired by this, we show that quantum detectors can resolve two frequencies from incoherent segments of the signal, irrespective of their separation, in contrast to what is known about classical detection schemes. The main idea behind these methods is to overcome the vanishing distinguishability in resolution problems by nullifying the projection noise.

Magnetic stimulation of curved nerves.

Magnetic stimulation of nerves is attracting increased attention recently, as it has been found to be useful in therapy of neural disorders in humans. In an effort to explain the mechanisms of magnetic stimulation, we focus in this paper on the dependence of magnetic stimulation on neuronal morphology and in particular on the importance of curvature of axonal bundles. Using the theory of passive membrane dynamics, we predict the threshold power (the minimum stimulation power required to initiate an action potential) of specific axonal morphologies. In the experimental section, we show that magnetic stimulation of the frog sciatic nerve follows our theoretical predictions. Furthermore, the voltage length constant of the nerve can be measured based on these results alone.

Identifying competencies for Australian health professionals working in international health.

A profile of the roles performed by Australian health professionals working in international health was constructed to identify the core competencies they require, and the implications for education and training of international health practitioners. The methods used included: literature review and document analysis of available training and education; an analysis of competencies required in job descriptions for international health positions; and consultations with key informants. The international health roles identified were classified in four main groups: Program Directors, Program Managers, Team Leaders and Health Specialists. Thirteen 'core' competencies were identified from the job analysis and key informant/group interviews. Contributing to international health development in resource poor countries requires high level cultural, interpersonal and teamwork competencies. Technical expertise in health disciplines is required, with flexibility to adapt to new situations. International health professionals need to combine public health competencies with high level personal maturity to respond to emerging challenges.

A device to measure the oxygen uptake rate of attached cells: importance in bioartificial organ design.

Quantification of the dependence of cellular oxygen uptake rate (OUR) on oxygen partial pressure is useful for the design and testing of bioartificial devices which utilize cells. Thus far, this information has only been obtained from suspended cells and from cells attached to microcarriers. In this work, a device was developed to obtain the dependence of OUR on oxygen partial pressure for anchorage-dependent cells cultured in standard culture dishes. The device is placed and sealed on the top of the culture dish, and holds a Clark polarographic mini-electrode flush with the bottom surface of the device. It also houses a motor to spin a magnetic stir bar within the cell chamber to insure that the medium is well-mixed. Several characteristics of the device--such as oxygen leakage into the device chamber, electrode-lag time, and linearity of the electrode at low oxygen partial pressures--were quantified and their potential effect on the values of Vm (maximal OUR) and K0.5 (oxygen partial pressure at which OUR is half-maximal) were evaluated. Comparison of Vm and K0.5 values obtained with this device with previously published values for suspended rat hepatocytes, Bacillus cereus, and E. coli indicated that the technique provides values accurate within 30% as long as the cell under study has a K0.5 greater than approximately 1.0 mmHg. For hepatocytes cultured on 0.05 mm thickness collagen gel for 1 day (n = 4) and 3 days (n = 6), Vm was found to be 0.38 +/- 0.12 and 0.25 +/- 0.09 nmol O2/S/10(6) cells, respectively, and K0.5 was found to be 5.6 +/- 0.5 and 3.3 +/- 0.6 mmHg, respectively. This technique should aid in predicting bioreactor conditions such as flow rate, cell density, distance of cell from flow, and gas phase oxygen partial pressure which can lead to oxygen limitations. In addition, further studies of the effect of factors such as extracellular matrix composition, metabolic substrate, and drugs on the dependence of OUR on oxygen partial pressure for many anchorage-dependent cell types can be pursued with this technique.

Pigmented epithelial tumours of the conjunctiva.

Two out of 60 conjunctival epithelial tumours reviewed between 1973 and 1989 were found to be pigmented. One tumour was a pigmented papilloma and the other a pigmented squamous cell carcinoma. The melanin pigment was found in epithelial tumour cells as well as in macrophages, dendritic melanocytes, and Langerhans cells. The distinction between the latter two types of cells was possible in one of the tumours only. Both tumours were found in dark-skinned white patients without any evidence of conjunctival acquired melanosis.

Effective diffusivity of galactose in calcium alginate gels containing immobilized Zymomonas mobilis.

The effective diffusivity of galactose was measured for calcium alginate gel membranes containing immobilized live Zymomonas mobilis cells at concentrations ranging from 0 to 150 g dry wt/L of gel. Since galactose is not taken up by living Z. mobilis organisms, the diffusion of this representative six-carbon sugar could be studied independently of sugar consumption. Various immobilized biomass loadings were achieved by two different techniques: addition of biomass at known concentrations to the sodium alginate solution before membrane formation and growth of cells in the gel to various biomass concentrations. The highest immobilized cell concentration, attained by in situ growth, corresponds to the maximum of this system, as growth beyond this maximum concentration led to disintegration of the gel membrane. The galactose effective diffusivity measurements for both methods of immobilized cell loading overlap within experimental error and follow the same general monotonic decline with entrapped biomass concentration. Most of the data fall below the upper bound predicted by Hashin and Shtrikman (1962) and show good agreement with the random pore model of Wakao and Smith (1962, 1964). Available effective diffusivity data from the literature provide evidence that the random pore model is an excellent predictor of sugar effective diffusivity in gel immobilized cell systems in general.

Improved depiction of small anatomic structures in MR images using Gaussian-weighted spirals and zero-filled interpolation.

Partial-volume artifacts reduce the contrast and continuity of small structures in magnetic resonance images. Zero-filled interpolation (ZFI) has been known for some time as a useful technique to reduce partial-volume artifacts and improve the appearance of small structures and edges. However, its use is limited by the fact that ZFI can exacerbate image artifacts. For example, it can exacerbate Gibbs ringing, also known as the truncation artifact, which manifests itself as spurious ringing around sharp edges. Currently, the most common technique to address this problem is post-acquisition filtering, which causes blurring in the image. Using ZFI in conjunction with a variable-density sampling method designed to reduce ringing is proposed as a possible solution to this problem. This approach is demonstrated with a Gaussian-weighted spiral and is compared to conventional spiral sampling both with and without the application of a filter used to reduce ringing. The two spiral sampling techniques are compared using simulations, phantom images, and in vivo brain images. The Gaussian-weighted spiral demonstrates reduced ringing without the loss of spatial resolution commonly associated with post-acquisition filtering. Additionally, this sampling technique is shown to work well in conjunction with ZFI to reduce partial-volume artifacts without the apparent increase in Gibbs ringing usually associated with zero-filled reconstruction. This approach will be most useful for imaging techniques such as MR angiography which are known to be sensitive to partial-volume effects, as well as when imaging anatomic regions associated with more severe Gibbs ringing.

The activity of cytochrome P450IA1 in stable cultured rat hepatocytes.

In this study, a stable, differentiated culture format (primary hepatocytes cultured between two layers of collagen gel) was used to study the effect of the inducer 3,3',4,4'-tetrachlorobiphenyl (TCB) on the activity of cytochrome P50IA1. P450IA1 (ethoxyresorufin O-deethylase) enzymatic activity was measured using the rate of conversion of ethoxyresorufin (ER) to resorufin (R). After 14 days of induction with 10(-6), M TCB, hepatocytes in the double collagen gel configuration exhibited a maximum activity of 180.3 +/- 46.8 pmol R/mug, DNA/hr (3.6 +/- 0.9 nmol R/10(6), cells/hr) compared with 34.9 +/- 3.8 pmol R/mug DNA/hr for cells cultured on a single layer of gel. At a TCB level of 10(-5), m, the P450IA1 activity in the double-gel configuration peaked at 220.8 +/- 37.0 pmol R/mug DNA/hr. Cessation of 10(-6), M TCB induction produced a decrease in activity to 25.8 +/- 4.1 pmol R/mug DNA/hr within 4 hr. Subsequent re-application of the inducer caused an increase in activity to 76.5 +/- 11.1 pmolR/mug DNA/hr within 6 hr, reaching a maximal value of 131.0 +/- 38.6 pmol R/mug DNA/hr within 12 hr. Since TCB is rapidly metabolized by hepatocytes, a continuous perfusion culture system was developed to examine the effect of exposure to a constant level of TCB. Continuous perfusion of the cells with 10(-8) or 10(-7), M TCB, resulted in activities significantly higher than those of cultures induced by daily application of induction medium. A mechanistic model of TCB-dependent induction of P450IA1 was developed using kinetic parameters estimated from static culture data. The model accurately predicted cyclic variations in P450IA1 activity in static culture, and the steady-state activity level of perfusion cultures. This work describes procedures for exposing stable hepatocyte cultures to either continuous or declining levels of consumable inducers and for measuring the activity of cytochrome P50IA1 in cultured hepatocytes by a non-invasive method.

Is integration of health services and manpower development possible? The Beer Sheva case study.

This paper presents a study of the organizational and management arrangements made to enhance integration between health services and health manpower development (HSMD) in the Negev region of Israel. The University Centre for Health Scinces (UCHS) in Beer Sheva provides a unique model for studying the deployment of academic resources in the development of an integrated health care system. This paper begins with a rationale for the establishment of the Centre. Then the organization is described and the factors which enhance and impede collaboration are analysed. Finally, the achievements of the UCHS to date are discussed.

Chondroma of the tongue. Report of two cases.

Lingual chondromas are very rare tumors. It can be assumed that chondromas of the tongue develop from heterotopic embryonal cartilage. Chondromas are usually seen on the lateral borders of the tongue. Because chondrosarcomas can appear in this location, wide excision of the lesions should be performed. The CO2 laser facilitates the excision, providing a dry surgical field. Two cases of lingual chondroma are presented and their probable cause discussed.

Effect of implant material properties on the performance of a hip joint replacement.

A composite material implant prosthesis for hip replacement has been developed. The design of the prosthesis substructure was based on investigation of the stress and strain fields that were developed in the human femur at the proximal end when a prosthesis stem had been inserted into it. The prosthesis stem structure was of unidirectional fibrous composite material core (graphite fibres in polysulfone matrix), wrapped with four layers of the same material but orientated at different angles. The orthotropic moduli of the outer layer are very close to the moduli of a human cortical bone in the vertical and circumferential directions. The moduli increased gradually from the outer layer to the inner core. A three-dimensional finite element model of the prosthesis and the bone has been constructed and loaded with the range of forces that might appear upon operation. The behaviour of the composite prosthesis and the femur was then compared with the intact femur and three other types of prosthesis materials, namely stainless steel, titanium, an isoelastic material and a hypothetical one with moduli identical to the cortical bone. The titanium has modulus of elasticity that is only half of the stainless steel. It was found that the composite prosthesis gave the best performance for most of the categories that were examined.

The clinical learning environment: nurses' perceptions of professional development in clinical settings.

Although the complexity of the working environment of Registered Nurses has been acknowledged, the relationship between the social context of work and perceptions of professional development have not been systematically studied. This research was designed to identify and explore the attributes of effective learning environments in clinical settings. Following an initial exploratory study of perceptions and experiences of registered and student nurses, a conceptual framework was developed and tested. The findings of the study ware based on responses to a questionnaire (n = 516) which was developed as a tool for assessing organisational and social factors associated with perceived professional development in clinical settings. There was a significant and positive correlation between professional development and six independent variables: Autonomy and Recognition, Role Clarity, Job Satisfaction, Quality of Supervision, Peer Support and Opportunities for Learning. These variables accounted for almost 40% of the variance in perceived professional development. There were differences between hospitals and wards on most of the independent variables suggesting that some wards and institutions are more conducive to learning than others. The implications of the findings in terms of further research and practice are discussed.

A comparative biomechanical study of the strength of the bony patella following dome cut or uniplanar cut in total knee arthroplasty.

This study was designed to investigate whether there is a difference in the strength of the bony patella following preparation either with a dome configuration or with a regular uniplanar cut in total knee arthroplasty. For each test 4 cadaveric patellae were used. Two of the 4 patellae were prepared with a regular uniplanar cut and 2 were prepared into a dome shape with a circumferential wall, using a concave reamer. The thickness of each patella after preparation was [figure 1 & 2: see text] 15 mm. The tests were performed using an impact drop weight apparatus. In the first two tests, which tested the resistance of the patella to tensile force and evaluated the strength of the patella by impact load while under tension, the soft tissues were torn, with no harm to the bony patella. In the third test, which evaluated the resistance of the patella without tension against impact load, the force required to fracture the dome-shaped patella was greater than for the traditional uniplanar cut (500 Kg vs 350 Kg). Dome shape with circumferential wall preparations of the bony patella in total knee arthroplasty were stronger in resisting external impact than the conventional uniplanar cut patella. This established the rationale for our use of the dome-shaped patella implant with a concave undersurface.

Selection and prediction of performance of entrants to GP training.

There are currently more applicants than available positions in The Royal Australian College of General Practitioners Vocational Training Program. This already entails a process to select entrants into the Program. Furthermore, any vocational program should be interested in attracting entrants who will complete their training and be successful practitioners. This paper aims to contribute to the debate on methods of selection and prediction in vocational programs for general practice.