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Biomedical subjects

J Funk

Publications and source records attributed to J Funk.

At least 19 recordsLinked to original sources

Molecular imaging: novel tools in visualizing rheumatoid arthritis.

Molecular imaging is a rapidly emerging field in biomedical research, aiming at the visualization, characterization and quantification of molecular and cellular processes non-invasively within intact living organisms. To sense biological processes such as gene expression, angiogenesis, apoptosis or cell trafficking in vivo, imaging reporter agents that interact specifically with molecular targets and appropriate imaging systems are currently under development. In rheumatoid arthritis, these novel tools will be used to evaluate physiological and pathophysiological processes, to facilitate diagnosis and monitor therapeutic regimens, to enable reliable prognosis and to support the development of new therapies. In this review, we summarize the basic principles of molecular imaging, such as the development of molecular imaging agents, the actual capabilities of different imaging modalities and the most recent advances in molecular imaging, demonstrating the potential of this technology. With regard to their applicability in rheumatic diseases, we discuss potential molecular targets, current experimental approaches and the future prospects for molecular imaging in rheumatoid arthritis.

Animals↗

[Diagnostic value of nerve fibre layer photography in glaucoma].

PURPOSE: Primary open-angle glaucoma is characterized by a loss of retinal nerve fibres. The aim of our present study was to evaluate the diagnostic value of retinal nerve fibre layer (RNFL) photography as a routine examination for the early diagnosis of glaucomatous damage. METHODS: Between 1991 and 2000 we monitored 96 patients with ocular hypertension in a prospective study. RNFL photography was performed in 91 subjects. These photos were evaluated by two independent observers. RESULTS: The mean image quality of the photos was mediocre. The correlation coefficient for the intraindividual reproducibility (image quality) was 0.713-0.863 (Kendall's coefficient). For the interindividual reproducibility the correlation coefficient was 0.541-0.581 (Somers' coefficient). Regarding the evaluation "RNFL defect yes/no", the correlations were better but there was a discrepancy between the observers. CONCLUSION: Quality, reproducibility and prognostic value of RNFL photography were disappointing. Although RNFL photography may be convincing and informative in several situations, it is not efficient as a routine technique for the early diagnosis of RNFL damage in glaucoma patients.

Aged↗

Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX.

OBJECTIVE: To evaluate the anti-arthritic effects of the new inflammation-targeted drug MTX-HSA and to investigate whether peripheral blood mononuclear cells (PBMC) are potential target cells for albumin-mediated drug delivery. METHODS: The murine model of collagen-induced arthritis (CIA) was used to measure the anti-arthritic effect of MTX, MTX-HSA or a combination of both (n = 30 to 35 per group). In addition, the uptake of fluorescence-labelled albumin (AFLc-HSA) in PBMC of 14 patients with RA was measured by fluorescence-activated cell sorting (FACS). RESULTS: In equivalent doses of 7.5 mg/kg intravenously (IV) twice a week, MTX-HSA is significantly (P<0.02) superior to MTX in inhibiting the development of CIA and reducing the joint count as well as the number of affected paws. When given in lower doses as combination therapy, both drugs act synergistically (P<0.03). A mean of 96, 72 and 64% of the CD14-, CD16- and CD20-positive cells from peripheral blood of rheumatoid arthritis (RA) patients showed an uptake of albumin after incubation with AFLc-HSA in vitro. This finding was not significantly different in comparison to healthy controls. In contrast, the number of CD3-positive cells taking up albumin is increased significantly in RA patients in comparison to controls (26.3 +/- 12.9% s.d. vs 11.6 +/- 7.3% s.d.; P = 0.005). CONCLUSION: The data show that the effectiveness of MTX-HSA in CIA is superior to MTX and that both drugs act synergistically. In addition, albumin appears to be taken up by peripheral blood cells, suggesting that they might be one of the potential target cells of this novel anti-arthritic treatment approach.

Animals↗

Sensitivity and specificity of scanning laser polarimetry using the GDx.

BACKGROUND/AIMS: To determine the sensitivity and the specificity of the GDx in the detection of (1) advanced glaucoma, (2) early glaucoma, and (3) nerve fibre bundle defects (NFBD). METHODS: Group A comprised 20 eyes with reproducible glaucomatous visual field defects confirmed by octopus perimetry, group B consisted of 10 eyes with normal visual fields but either glaucomatous NFBD or deterioration of the disc over time clearly visible upon flicker comparison, and group C included 16 eyes with glaucomatous or non-glaucomatous NFBD clearly visible on red free photographs. Forty four eyes of 22 healthy volunteers served as controls. The GDx printouts of all subjects were evaluated by three independent observers in a masked fashion and without the clinical picture of the optic disc. Two of the three observers (SK, UH) were GDx experts, one (KUL) was an untrained GDx user. RESULTS: Among the GDx experts, sensitivity/specificity was 100%/100% (SK) and 90%/100% (UH) in detecting advanced glaucoma, and 100%/100% (SK) and 90%/100% (UH) in detecting early glaucoma. The sensitivity in detecting NFBD was only 37.5% (SK and UH). For the untrained GDx user the corresponding values were 50%/100% (group A), 20%/100% (group B), and 12.5%/91% (group C). CONCLUSION: Detection of (early) glaucoma damage by the GDx, evaluated by trained experts, can be extremely high. To optimise its benefit in clinical routine training in interpreting GDx printouts is highly recommended. Detection of localised NFBD is crucial, even for experts.

Diagnostic Techniques, Ophthalmological↗

[Glaucoma diagnosis with the GDx and measurement of nerve fibre thickness (RTA)].

Damage of retinal nerve fibres is an early sign of glaucoma.Therefore, a quantitative determination of nerve fibres would be an ideal technique for early glaucoma diagnosis. This can be realized by the GDx which uses nerve fibre polarimetry to measure the thickness of the parapapillary nerve fibre layer.A single GDx measurement in a glaucoma patient may be an important adjunct to the clinical findings.However, at present the method is not suitable for general screening. Presumably the most important application of the device is longitudinal monitoring. In contrast to the GDx,RTA determines the thickness of the whole retina, not specifically the nerve fibre layer. This might be a reason why the discrimination between normal subjects and glaucoma patients is somewhat more difficult than with the GDx.Again, longitudinal monitoring should be the most common application of the RTA in glaucoma patients. Besides glaucoma,RTA also allows examination of macular pathologies.RTA is a promising new technique which so far is not as frequently used as the GDx or the HRT.

Disease Progression↗

Influence of different tumour types on natural cytotoxicity (NK cell activity) and mitogen-induced lymphocyte proliferation in isolated blood lymphocytes from 110 dogs with tumours.

The cell-mediated immune response of blood lymphocytes from 110 untreated dogs with different tumours was evaluated. The influence of different tumour types on the cellular immune system was examined by assessing the percentage of isolated large granular lymphocytes (LGL), in vitro natural cytotoxicity and mitogen-induced lymphocyte proliferation. Although the overall natural cytotoxicity of dogs with different tumours was decreased, the overall difference from control values was not statistically significant. However, mitogen-induced lymphocyte proliferation was significantly depressed in dogs with tumours in comparison with the controls. Dogs with mammary carcinomas showed significantly lower natural cytotoxicity than controls and dogs with myeloid neoplasms showed significantly lower mitogen-induced lymphocyte proliferation. Abnormalities exist not only in natural cytotoxicity but also in mitogen-induced lymphocyte proliferation. For the dog, this is the first study to assess the influence of different tumours using a combined evaluation of natural cytotoxicity and mitogen-induced lymphocyte proliferation in such a large number of animals.

Animals↗

Retinal thickness decreases with age: an OCT study.

BACKGROUND/AIM: In three dimensional optic disc tomography a reference plane is required to calculate optic disc rim or cup values. The position of the reference plane often depends on the retinal thickness at the temporal disc margin. Originally it was assumed that the retinal thickness at the temporal disc margin is independent of age. The aim of the study was to check this hypothesis using optical coherence tomography, and additionally to determine the reproducibility of OCT measurements in this area. METHODS: 100 eyes of 100 healthy volunteers were included in this study. Three OCT scans were performed on each eye. The scans were aligned vertically and placed at the temporal edge of the optic disc. For each eye, the thickness of the whole retina as well as the thickness of the retinal nerve fibre layer were calculated together with their coefficients of variation. Thereafter retinal thickness and nerve fibre layer thickness were correlated with age. RESULTS: The mean retinal thickness was 249 (SD 22) micro m. The mean nerve fibre layer thickness was 109 (22) micro m. The mean coefficients of variation were 3.5% (total retinal thickness) and 8.0% (nerve fibre layer thickness). Both the total retinal thickness and the nerve fibre layer thickness were significantly correlated with age (total retina: y = 269.5 - 0.53 x x; R(2) = 0.133; p = 0.0002, nerve fibre layer: y = 126.8 - 0.44 x x; R(2) = 0.094; p<0.0019. CONCLUSIONS: Using OCT scans the total retinal thickness can be calculated with high reproducibility (coefficient of variation = 3.5%). The reproducibility of nerve fibre layer thickness measurements is clearly lower (coefficient of variation = 8.0%). Both the total retinal thickness and the nerve fibre layer thickness significantly decrease with age. This influence of the age related decrease in RNFL/retinal thickness on the reference plane, however, is negligible.

Adolescent↗

First outbreak of callitrichid hepatitis in Germany: genetic characterization of the causative lymphocytic choriomeningitis virus strains.

Callitrichid hepatitis (CH) is a highly fatal, rodent-borne zoonosis of New World primates (family Callitrichidae) caused by lymphocytic choriomeningitis virus (LCMV). It is unclear whether virulence in Callitrichidae is associated with specific genetic or phylogenetic markers of the virus as only a partial S RNA sequence of a single CH-associated isolate is known. In a period of 10 months, three pygmy marmosets (Cebuella pygmaea) and one Goeldi's monkey (Callimico goeldii) died from CH in a German zoo. LCMV was most likely transmitted by wild mice. Infection was associated with characteristic histopathological lesions in liver, brain, and lymphoid tissue. Virus sequences from all callitrichids and a captured mouse were > or =99.2% identical. LCMV strains from a pygmy marmoset and the Goeldi's monkey were isolated in cell culture and the 3.4-kb S RNA was completely sequenced. Both strains differed considerably in their genetic and phylogenetic characteristics from known LCMV strains, including the previously described CH-associated strain. These data show that CH is widespread and can be caused by distantly related LCMV strains.

Amino Acid Sequence↗

[Diode laser cyclophotocoagulation as the primary surgical intervention in glaucoma].

BACKGROUND: Diode laser cyclophotocoagulation is widely accepted as the therapy of choice in severe glaucoma cases. It is especially performed after failure of other kinds of treatment. We wanted to know whether it is also suitable as a primary surgical procedure after failure of medical treatment. PATIENTS AND METHODS: We retrospectively evaluated the charts of patients scheduled for cyclophotocoagulation as a primary surgical treatment between February 1997 and May 1998. Usually 15 burns (2000 mW, 2.5 s) were applied per treatment session. The mean age was 75.5 +/- 7.4 years (range: 63-86). The mean follow-up was 17.5 months (range: 6-32). RESULTS: Altogether 25 eyes of 20 patients could be included in the study. There was a mean reduction of the intraocular pressure from 29.9 mmHg preoperatively to 17.4 mmHg postoperatively = 41.6%. In three cases (12%) repeated treatment was necessary. No severe complications such as endophthalmitis or phthisis bulbi were observed. No acute postoperative elevation of intraocular pressure > or = 40 mmHg occurred. Visual acuity remained stable during the follow-up in all eyes with a preoperative measurement of 20/60. DISCUSSION: Diode laser cyclophotocoagulation is suitable as a primary surgical procedure. We mostly perform it instead of filtering procedures when the patient refuses the filtering operation or when the patient is not able to visit an ophthalmologist for regular aftercare.

Aged↗

Correlation between central corneal thickness, applanation tonometry, and direct intracameral IOP readings.

BACKGROUND: Several authors reported incorrect high intraocular pressure (IOP) values in eyes with a thick cornea using applanation tonometry. This hypothesis was checked by comparing applanation tonometry with direct intracameral manometry. METHODS: 73 patients, scheduled for intraocular surgery, were enrolled. Immediately before surgery, the following were registered: (i) central corneal thickness (CCT), (ii) applanatory IOP (Perkins/Tonopen), and (iii) intracameral IOP. RESULTS: The difference between applanatory and intraocular measurements was completely independent of CCT (y= -3.43 + 3.8x; where y is the difference between applanatory and intracamerally measured IOP (mm Hg) and x is CCT (mm); r(2) = 0.002; p = 0.72). CONCLUSIONS: There is no systematic error of applanation tonometry with increasing CCT. Therefore it is inadequate to recalculate IOP based on regression formula of applanatory IOP versus CCT.

Adolescent↗

[Intraocular pressure reduction by endoscopically controlled erbium:YAG goniotomy].

BACKGROUND: Microperforations of the trabecular meshwork can be made using an endoscope guided Er:YAG laser. As shown in enucleated human melanoma eyes, these microperforations are not accompanied by thermal damage of the surrounding tissue. We now report our first clinical results using a commercially available endoscope/laser system for performing this particular kind of goniotomy. PATIENTS AND METHOD: A combined cataract extraction and Er:YAG goniotomy was performed in 24 eyes of 20 patients. Seventeen eyes were reexamined after a minimum follow-up of 4 months (mean 6.5 months, max. 12 months). The results were compared to a control group having only the cataract operation (14 eyes). RESULTS: After combined cataract operation and Er:YAG goniotomy, mean intraocular pressure dropped from 21.8 to 15.5 mmHg. Intraocular pressure regulation was successful in 88% of these cases. In contrast to this, the intraocular pressure reduction in eyes having only the cataract operation was much less pronounced (mean intraocular pressure preoperative 20.0, postoperative 17.4, success rate 35%). CONCLUSION: The first results with our particular endoscope/laser system are encouraging. Other groups using comparable devices have reported similar success rates. We hope that the endoscopic Er:YAG goniotomy may become a minimally invasive type of glaucoma surgery in the near future.

Aged↗

[Measuring retinal circulation with the Heidelberg retinal flowmeter: reproducibility of data and no effect of metipranolol in normal probands].

PURPOSE: We wanted to know whether topical Metipranolol has any effect on ocular blood flow. Before starting this investigation using the Heidelberg Retina Flowmeter, we studied the reproducibility of this device. METHOD: Retinal blood flow was determined in 15 healthy volunteers. Altogether, each volunteer was measured 20 times (4 different days with 5 pictures each). Coefficients of variation were calculated for both, the short term fluctuation and the long term fluctuation. After that, the effect of metipranolol was tested in 14 of the 15 volunteers mentioned above. This was done in a randomized, placebo controlled, double masked and crossover designed study. RESULTS: The mean coefficients of variation were 21% for the short term fluctuation and 13% for the long term fluctuation. There was a significant effect of learning, i.e. coefficients of variation decreased with increasing experience of the investigator (MVR). Blood flow values did not differ significantly between metipranolol and placebo. CONCLUSIONS: 1. The reproducibility of blood flow values measured with the Heidelberg Retina flowmeter are sufficient, at least if the device is used in clinical studies. When performing those studies, the learning curve of the investigator should be taken into account. 2. The topical application of metipranolol does not alter the retinal blood flow in healthy volunteers.

Adult↗

Children and electronic games: a comparison of parents' and children's perceptions of children's habits and preferences in a United States sample.

Despite the popularity of violent electronic games, anecdotal evidence suggests that many parents lack even basic information about children's game-playing habits. The goal of the present study was to examine parental knowledge of children's electronic game-playing habits by assessing the congruence between children's and parents' perceptions of child's playing time, parental supervision, game preference, and reaction to actual game-playing. 35 children in Grades 3 to 5 and one parent of each child completed a background questionnaire and played either a violent or nonviolent electronic game. In paired comparisons, parents reported significantly higher estimates of supervision time than children. Most parents either named an incorrect game or were not able to guess their child's favorite game. In 70% of these incorrect matches, children described their favorite game as violent. Parents may underestimate their child's exposure to violence in electronic games. After playing the same electronic game as part of the study, parents reported significantly higher frustration than children. Higher frustration with game-playing could contribute to deficits in parental knowledge of children's playing habits.

Adult↗

[Endoscopically controlled erbium YAG laser goniotomy. Initial preclinical trials].

INTRODUCTION: Endoscopic erbium-YAG laser treatment is a new approach in glaucoma surgery. In contrast to conventional laser systems, the photoablative erbium-YAG laser allows microperforations of the trabecular meshwork without thermal side effects. We report our first preclinical trials using this new system. METHOD: We used the Endognost system (Schwind Co.). The device combines an endoscope and illumination fiber (0.5 mm diameter), laser fiber (0.5 mm) and a irrigation tube in one probe with a 1.1 mm external diameter. The Endognost system was tested in porcine and enucleated human eyes. All eyes were examined histologically. RESULTS: The endoscopic view into the anterior chamber allows for precise allocation of the laser pulses. Using a single pulse mode with 10 mJ a micropuncture of the trabecular meshwork can be achieved without damaging the adjacent tissue. Using multiple pulses or higher energy levels leads to damage of the posterior wall of Schlemm's canal and to thermal side effects. CONCLUSIONS: Endoscope guided erbium-YAG laser effects on trabecular tissue are comparable to those produced by a 308 nm excimer laser. Therefore, a similar reduction in intraocular pressure can be expected.

Animals↗

Imaging of the optic disc in glaucoma: which way to go?

Less than 10 years ago, fundus photography was believed to be the only method to document optic disc changes in glaucoma. Since then, many sophisticated electronic devices have been developed to supersede conventional photography. At the moment, confocal laser scanning tomography, nerve fiber layer polarimetry, and optical coherence tomography are the most popular techniques. The current status of optic disc imaging in glaucoma can (in our very subjective opinion) be summarized as follows. Confocal laser scanning tomography is the most comprehensively tested electronic modality. It is perhaps the method of choice in major glaucoma centers. Nerve fiber layer polarimetry has forged ahead during the past 2 years and may become an alternative to confocal laser scanning tomography in the future. Optical coherence tomography is a fascinating technique, which may also become important in the future. Right now, however, it is still in the experimental stage. Conventional disc photography--despite all those new techniques--still has its place. Perhaps it is the method of choice in routine glaucoma practice, except those clinics that can afford one of the "high tech" machines.

Diagnostic Imaging↗