ISCEV and IPS guideline for the full-field stimulus test (FST).

The full-field stimulus test (FST) is a psychophysical technique designed for the measurement of visual function in low vision. The method involves the use of a ganzfeld stimulator, as used in routine full-field electroretinography, to deliver full-field flashes of light. This guideline was developed jointly by the International Society for Clinical Electrophysiology of Vision (ISCEV) and Imaging and Perimetry Society (IPS) in order to provide technical information, promote consistency of testing and reporting, and encourage convergence of methods for FST. It is intended to aid practitioners and guide the formulation of FST protocols, with a view to future standardisation.

Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes.

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune ß-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.

Conjugation of a peptide autoantigen to gold nanoparticles for intradermally administered antigen specific immunotherapy.

Antigen specific immunotherapy aims to tolerise patients to specific autoantigens that are responsible for the pathology of an autoimmune disease. Immune tolerance is generated in conditions where the immune response is suppressed and thus gold nanoparticles (AuNPs) are an attractive drug delivery platform due to their anti-inflammatory effects and their potential to facilitate temporal and spatial delivery of a peptide autoantigen in conjunction with pro-tolerogenic elements. In this study we have covalently attached an autoantigen, currently under clinical evaluation for the treatment of type 1 diabetes (PIC19-A3 peptide), to AuNPs to create nanoscale (<5 nm), negatively charged (-40 to -60 mV) AuNP-peptide complexes for immunotherapy. We also employ a clinically approved microneedle delivery system, MicronJet600, to facilitate minimally-invasive intradermal delivery of the nanoparticle constructs to target skin-resident antigen presenting cells, which are known to be apposite target cells for immunotherapy. The AuNP-peptide complexes remain physically stable upon extrusion through microneedles and when delivered into ex vivo human skin they are able to diffuse rapidly and widely throughout the dermis (their site of deposition) and, perhaps more surprisingly, the overlying epidermal layer. Intracellular uptake was extensive, with Langerhans cells proving to be the most efficient cells at internalising the AuNP-peptide complex (94% of the local population within the treated region of skin). In vitro studies showed that uptake of the AuNP-peptide complexes by dendritic cells reduced the capacity of these cells to activate naïve T cells. This indicator of biological functionality encourages further development of the AuNP-peptide formulation, which is now being evaluated in clinical trials.

A robust viologen and Mn-based porous coordination polymer with two types of Lewis acid sites providing high affinity for H2O, CO2 and NH3.

A novel porous coordination polymer [Mn(pc3)(H2O)2]·xH2O (3 < x < 4) is synthesized in water at pH = 7 using the anionic viologen-carboxylate ligand 4,4'-bipyridinium,1,1'-bis-(2,4-dicarboxyphenyl) (pc32-). Dehydration of the material results in the formation of open pores containing two types of accessible Lewis acid sites: exposed Mn2+ cations and N+ atoms of viologen units. Due to this property the PCP shows high affinity and capacity in the adsorption of H2O, CO2 and NH3. Despite the presence of strong adsorption sites this material is stable in liquid water and in gaseous NH3.

Hydrodynamic gene delivery in human skin using a hollow microneedle device.

Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVß and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50µL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVß reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery.

A vitamin K epoxide reductase-oxidase complex gene polymorphism (-1639G>A) and interindividual variability in the dose-effect of vitamin K antagonists.

A daily dose of vitamin K antagonists (VKAs) may vary and its range depends on various interrelated factors. Low responsiveness to VKA (defined as a failure to achieve a target international normalized ratio [INR]) is associated with polymorphisms of the vitamin K epoxide reductase-oxidase complex gene (VKORC1). A highly prevalent promoter single-nucleotide polymorphism (VKORC1-1639 G>A, rs17878363) impairs VKORC1 expression and determines the interindividual variability of the target INR. We studied 57 patients receiving oral anticoagulation, including 50 subjects treated with acenocoumarol (mean dose: 5.7+/-2.3 mg/day) and 7 treated with warfarin (mean dose: 9.6+/-4.2 mg/day). The indications for the use of oral anticoagulant therapy were as follows: deep-vein thrombosis (N = 23); pulmonary embolism (N = 20); arterial thrombosis (N = 5); stroke (N = 4); atrial fibrillation with transient ischemic attacks (N = 2), and history of multiple thromboembolic events (N = 3). Identification of the VKORC1 genomic variation was performed using DNA sequencing methods. The prevalence of the mutated allele (VKORC1 -1639A) was 41%. The VKORC1 -1639G allele carriers required a higher daily dose of acenocoumarol (5.9+/-1.9 mg) than the noncarriers (4.1+/-3.3 mg; P < 0.001). All of 5 low responders (who failed to achieve a target INR using standard dose requirements of VKAs) were homozygous for the 1639G allele. Low responders did not differ from good responders with respect to age, gender, and body mass index. Our findings suggest the potential benefits from pharmacogenetic testing, and provide evidence that the VKORC1 -1639 G>A gene polymorphism may explain at least in part the low responsiveness to acenocoumarol.

Molecular epidemiology of antibiotic-resistant gram-negative bacilli in a neonatal intensive care unit during a nonoutbreak period.

OBJECTIVE: Gram-negative organisms that are resistant to parenteral antibiotics are a growing threat to hospitalized patients. This study was conducted to define the epidemiologic characteristics of these organisms during a nonoutbreak period in a neonatal intensive care unit (NICU). METHODS: Nasopharyngeal and rectal swab specimens were obtained 3 times a week from every infant in a tertiary care NICU during a 12-month period. Specimens were processed to identify aerobic Gram-negative species resistant to gentamicin, piperacillin-tazobactam, or ceftazidime. Selected clinical parameters were tested for their association with colonization with a resistant organism. Restriction endonuclease digests of genomic DNA were derived from isolates of the most frequently occurring species. The fragments were analyzed by pulsed-field gel electrophoresis (PFGE) to determine the genetic relatedness of the various isolates and thereby determine the length of colonization, the frequency of horizontal transmission, and the size and duration of clusters. RESULTS: A total of 101 infants (8.6%) of 1180 admissions were colonized with at least 1 antibiotic-resistant bacillus before NICU discharge. Multiple parameters indicating a prolonged, complicated NICU course were associated with resistant colonization, including gestational age, length of stay, and exposure to several classes of antibiotics. Colonization with resistant bacilli occurred as early as the first NICU day, but acquisition continued throughout the infants' stay. A total of 436 isolates were analyzed by PFGE. On the basis of this molecular analysis, it was determined that duration of colonization was usually very short; the median for all species tested was <1 week. In addition, cross-colonization occurred in only 12% of all PFGE-analyzed isolates. Most clusters of cross-colonized infants were small, with the majority involving only 2 patients. CONCLUSIONS: During endemic periods, acquisition of antibiotic-resistant Gram-negative bacilli in the NICU may occur very soon after admission, but colonization continues over many weeks of NICU stay. The duration of colonization with resistant bacilli is short, and horizontal transmission is unusual. These characteristics suggest a gradual but temporary incorporation of these organisms from the NICU environment into the nascent newborn microflora over time with little cross-colonization. These observations may aid the rational development of infection-control strategies to contain the reservoir of resistant Gram-negative organisms in the NICU.antibiotic resistance, Gram-negative bacilli, neonatal intensive care, antibiotic utilization, colonization, pulsed-field gel electrophoresis.

Abnormal gait in neurologic disease.

For most people, walking is an automatic, unconscious activity, characteristic of each individual. Patterns of gait can be reflective of a person's body structure, occupation, and personality, as well as health status. Most parents who watch an infant beginning to walk realize that locomotion is a highly complex, learned process. Years of training and practice are necessary for the sensory-motor system to become adept at automatically generating the motor commands necessary to permit walking without conscious effort. The characteristic adult pattern of walking does not emerge until up to 7 to 9 years of age, after the neuromusculoskeletal systems have undergone constant modification and development of improved neural controls. Important information pertinent to the patient's health status can be obtained by observing his or her manner of walking. This article will review abnormal gait patterns due to nervous system dysfunction. To help understand abnormal gaits, a brief review of the underlying components of walking is necessary.

Bone scintigraphy: a review of the procedure and its applications.

Bone scintigraphy (bone scanning) is a sensitive diagnostic tool used to detect the presence and extent of primary and secondary bone disease. Unlike X-rays, MRI, and CT scans, which focus primarily on structural anatomy, bone scans depict the dynamic physiologic response of bone to an insult. We review bone scanning principles, their indication in eye care, and demonstrations of their use in eye involvement from both primary and metastatic bone disease.

Co-management of patients with hypertension.

Information provided by doctors of optometry to the primary care providers of patients with hypertension provides one of the few objective means of assessing the status of these patients. The optometrist may also be the first to suspect primary or secondary hypertension in the course of a comprehensive eye examination. In this paper the pathophysiology of essential, malignant, and secondary hypertension is reviewed. The treatment and management of the systemic and ocular effects of hypertension are discussed along with the pivotal role that doctors of optometry play in co-managing patients with hypertension.

The optometric assessment of neurologic function.

BACKGROUND: As a direct extension of the nervous system, the eye may be involved in a number of nervous system diseases and disorders. METHODS: The previous ophthalmic and medical literature was evaluated and organized into an orderly review of the literature with recommendations for the examination of patients with neurologic dysfunctions. RESULTS: Many of the appropriate tests for the assessment of neurologic function can be readily performed by optometrists in the clinical setting. CONCLUSIONS. The screening of neurologic function by optometrists is important in many ways. The optometrist can gain significant insight in the ocular and systemic diagnoses associated with neurologic disease by utilizing the appropriate clinical tests and as a result then communicate more effectively with neurologists and other health care practitioners.

Optic nerve trauma.

Trauma to the optic nerve may be direct, such as from a penetrating object, or indirect, which may result despite lack of direct contact of an object with the nerve. Although indirect injury initially causes no change in the appearance of the nerve head, within a matter of weeks optic atrophy will be manifest. The pathophysiology of nerve damage is incompletely understood. Management is controversial; steroid therapy has been advocated, as has surgical decompression of the nerve. Indirect injuries affecting the optic nerve may also result from torsional rotation of the globe (avulsion) and from subdural or subarachnoid hemorrhage (Terson's syndrome). There is no treatment for optic nerve avulsion; the unaffected eye should be protected with appropriate eyewear. Hemorrhaging in the retina and vitreous in Terson's syndrome should be monitored for resolution and risk of retinal detachment. Computed tomography may be necessary if subarachnoid or intracranial hemorrhages are suspected.

[Heart transplantation in the doctors' opinion (results of a questionnaire)]. / Przeszczep serca w opinii lekarzy (wyniki ankiety).

This report presents the results of the survey aimed to evaluate physicians' attitude and personal opinion on heart transplantation. The study comprised 124 people: 92 physicians (internal medicine) and 32 students of the Faculty of Medicine (sixth year) in Cracow. None of the responders was directly or indirectly involved in cardiac transplantation. Responders were assessed using questionnaire consisting of 17 questions. Participation was voluntary and anonymous. Percentage analysis and non-parametric chi-2 test were applied in statistical analysis of the results. As many as 91.9% responders declared themselves as heart transplantation supporters. As the most important causes of small number of heart transplantations in Poland the following factors were considered: inadequate quantity of cardiosurgical centers and qualified medical staff (72%), shortage of heart donors (53%), insufficient knowledge of the physician on donor's qualification (49%), excessive cost of transplantation and postoperative management (46%). Only 11.3% responders have chosen right criteria for brain death out of given possibilities, 4% identified the factors excluding potential heart donors, 89.5% have known who was authorized to diagnose brain death and 59.6% knew where to refer the donor. The fact that after cardiac transplantation the patient requires long-term immunosuppressive treatment was recognized by 87%. Only 8.3% was able to indicate the essential drug - cyclosporin A, whereas 56.1% of responders were willing to treat the patients after heart transplantation. No statistical correlation between the above-mentioned results and the place of work, degree of specialization, professional experience of the physician was found.(ABSTRACT TRUNCATED AT 250 WORDS)

[Opinions and fears of patients waiting for heart transplantation. (results of questionnaire)]. / Opinie i leki chorych oczekujacych na przeszczep serca. (wyniki ankiety).

The purpose of the study was to assess the quality of life and opinions of heart transplant candidates about transplantation and to evaluate some psychological aspects of anticipation of the procedure. The study comprised 49 patients from the Department of Cardiac and Vascular Surgery according to a list of potential candidates from January 1991. The special questionnaire prepared by the authors was applied in the study. The main topics were: severity and treatment of heart disease, method of informing about necessity of operation and basics of transplantation, factors contributing to the ultimate decision, opinions about problems of donors and psychological aspects of disease and transplantation, especially anxiety and fear. 39 answers (34 men, 5 woman, mean age--49.6 years) were received, including 10 reports of patient's death. Respondents evaluated their compensation of illness as bad or average nearly in equal proportions, 48.3% and 51.7% respectively. They were treated in the intensive care units on average 2.6 times a year. 96.6% assessed highly the method of informing about heart transplantation, consisting of a private conversation with a physician. A similar proportion of respondents (93.1%) began to show concern about problems associated with this procedure. Up to 77.8% declared the desire of increasing their knowledge on that score emphasizing the significance of information coming from physicians. The majority of respondents were interested in postoperative management--but 40.4% stated that they did not know anything about it. 58.6% consent immediately after transplantation had been proposed by the physician.(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodative accuracy to harmonically related complex grating patterns and their components.

Monocular steady-state accommodation was measured to harmonically related complex grating patterns and their components to determine the contribution of the various spatial waveforms to accommodative accuracy. Accommodative accuracy was greater for those waveforms containing summed odd-harmonic spatial components than for those waveforms with specific spatial components either removed or isolated. The results suggest that the contrast gradient produced by the summed waveforms, rather than the presence of any particular subset of spatial frequency components per se, was a critical factor for accurate accommodation.

Multicenter clinical trial and laboratory utilization of an enzymatic detection method for gonococcal antigens.

Seven institutions participated in a comparative study evaluating standard culture method and a new enzyme immunoassay (EIA, Gonozyme, Abbott Diagnostics) for the detection of Neisseria gonorrhoeae. Five hundred twenty-three patients were entered from hospitals of various sizes representing different population densities, ethnic and economic sectors, and gonococcal prevalence. Statistical analysis showed sensitivity, specificity, and positive and negative predictive values of 80.3%, 94.6%, 66.2%, and 97.3% for the total population tested. For the high-prevalence (greater than 15%) population the respective values were as follows: 78.6%, 91.5%, 68.8%, and 94.7%. Specimens from females had a lower sensitivity than those from males. In the low-prevalence population (less than 10%) results were as follows: 100%, 97.8%, 50%, and 100%. A cost comparison emphasized the benefit of the Gram's stain and culture. It also indicated that, unless batched or assayed at high volume, Gonozyme is not cost competitive for laboratories using standard culture methods. The impact of the EIA method, in general, and Gonozyme, specifically, on the microbiology section also was investigated. Integration would require altering of established work patterns and loss of flexibility and freedom of standard plating technics. The fact that Gonozyme is a "presumptive" test limits it to being a complementary assay, not an alternative. The authors conclude that Gonozyme is optimally suited to a high-volume laboratory, screening a low-prevalence female outpatient population, where specimen transport is a problem and gonococcal resistance to penicillin has not been demonstrated. This would include sexually transmitted disease clinics, reference laboratories, and state health departments.

EF-4 bacteremia in a patient with hepatic carcinoid.

An organism similar to EF-4, a member of the unclassified group of unusual gram-negative bacilli of Elizabeth O. King, was isolated from the blood of a 65-year-old female with previously diagnosed carcinoid of the liver. We believe this to be the first report of systemic infection with this organism.

Infection caused by thymidine-requiring, trimethoprim-resistant bacteria.

We first noted the appearance of thymidine-requiring, gram-negative bacilli in clinical specimens 2 years ago. Since then we have seen 10 patients colonized or infected with these organisms. These strains do not grow on Mueller-Hinton media, growth on MacConkey agar is variable, and growth in API 20E (Analytab Products) and Enterobacteriaceae-Plus Cards (AutoMicrobic system; Vitek Systems Inc.) is inadequate for reliable identifications. Thymidine-requiring organisms are routinely resistant to sulfonamides and trimethoprim. Infection or colonization is associated with previous sulfamethoxazole-trimethoprim therapy in most cases. Of 10 patients, 1 had septicemia of urinary tract origin, 5 had urinary tract colonization or infection, 2 had wound colonization, and two had colonization of respiratory secretions. Thymidine-requiring, gram-negative bacilli can be pathogens and present potential problems in diagnosis, identification, and susceptibility testing.