Biomedical subjects

Michael Larsen

Publications and source records attributed to Michael Larsen.

12 recordsLinked to original sources

PubMed2003

Evaluation of prevalence and clinical implications of anthelmintic resistance in gastrointestinal nematodes in goats.

OBJECTIVE: To determine prevalence of resistance to all anthelmintics that are commonly used to treat gastrointestinal nematodes (GINs) in goats. DESIGN: Prospective study. ANIMALS: 777 goats. PROCEDURE: On each farm, goats were assigned to 1 of 5 treatment groups: untreated controls, albendazole (20 mg/kg [9.0 mg/lb], p.o., once), ivermectin (0.4 mg/kg [0.18 mg/lb], p.o., once), levamisole (12 mg/kg [5.4 mg/lb], p.o., once), or moxidectin (0.4 mg/kg, p.o., once), except on 3 farms where albendazole was omitted. Fecal samples were collected 2 weeks after treatment for determination of fecal egg counts (FECs), and percentage reductions were calculated by comparing data from anthelmintic-treated and control groups. Nematode populations were categorized as susceptible, suspected resistant, or resistant by use of guidelines published by the World Association for the Advancement of Veterinary Parasitology. RESULTS: Resistance to albendazole was found on 14 of 15 farms, and resistance to ivermectin, levamisole, and moxidectin was found on 17, 6, and 1 of 18 farms, respectively. Suspected resistance to levamisole and moxidectin was found on 4 and 3 farms, respectively. Resistance to multiple anthelmintics (albendazole and ivermectin) was found on 14 of 15 farms and to albendazole, ivermectin, and levamisole on 5 of 15 farms. Mean overall FEC reduction percentages for albendazole, ivermectin, levamisole, and moxidectin were 67, 54, 94, and 99%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Anthelmintic resistance in GINs of goats is highly prevalent in the southern United States. The high prevalence of resistance to multiple anthelmintics emphasizes the need for reexamination of nematode control practices.

Albendazole↗

PubMed2003

Kinetics of retinal lipoprotein precipitation and elimination after closure of subretinal new vessels.

PURPOSE: To study the kinetics of retinal precipitation and elimination of lipoprotein in relation to photodynamic therapy of subretinal new vessels. METHODS: This was a retrospective observational study of subretinal precipitate before and after photodynamic therapy for subfoveal new vessels secondary to age-related macular degeneration in 14 eyes demonstrating precipitate at one or more visits, using digital red-free gray-scale fundus photography, intravenous fluorescein angiography, optical coherence tomography, and morphometric mapping. RESULTS: In 14 eyes of 14 patients, the area covered by lipoprotein precipitate increased from a mean of 0.54 optic disc areas (range, 0-2.61) before treatment to a mean of 0.65 optic disc areas (range, 0.01-3.04) at 45 d after treatment (P = 0.18). Eyes with a serous detachment at baseline, before the initial treatment (n = 10) demonstrated more treatment-related precipitation than eyes without a serous detachment at baseline (n = 4; P = 0.034). Two eyes with a large amount of precipitate and a long follow-up demonstrated net elimination of precipitate from approximately 100 days after the initial treatment, with uniexponential precipitate half-lives of 43 and 32 days. CONCLUSIONS: Photodynamic therapy for subfoveal new vessels may be associated with retinal precipitation of lipoprotein, presumably because early extraction of water and salts from the subretinal fluid increases the concentration of leaked plasma proteins. Despite reperfusion of the subretinal vessels, macromolecular leakage appears to cease within 100 days, indicating that functional maturation of the new vessels has occurred, with an associated decrease in pore size.

Aged↗

PubMed2003

Automated detection of diabetic retinopathy in a fundus photographic screening population.

PURPOSE: To evaluate the performance of an automated fundus photographic image-analysis algorithm in high-sensitivity and/or high-specificity segregation of patients with diabetes with untreated diabetic retinopathy from those without retinopathy. METHODS: This was a retrospective cross-sectional study of 260 consecutive nonphotocoagulated eyes in 137 diabetic patients attending routine photographic retinopathy screening. Mydriatic 60 degrees fundus photography on 35-mm color transparency film was used, with a single fovea-centered field. Routine grading was based on visual examination of slide-mounted transparencies. Reference grading was performed with specific emphasis on achieving high sensitivity. Computer-assisted automated red lesion detection was performed on digitized transparencies. RESULTS: When applied in a screening population comprising patients with diabetes with untreated diabetic retinopathy in any eye and patients with diabetes without retinopathy, the automated lesion detection correctly identified 90.1% of patients with retinopathy and 81.3% of patients without retinopathy. A per-eye analysis for methodological purposes demonstrated that the automated lesion detection could be adapted to simulate various visual evaluation strategies. When adapted at high sensitivity, the automated system demonstrated sensitivity at 93.1% and specificity at 71.6%. When adapted at high specificity the automated system demonstrated sensitivity at 76.4% and specificity at 96.6%, closely matching routine visual grading at sensitivity 76.4% and specificity 98.3%. CONCLUSIONS: Automated detection of untreated diabetic retinopathy in fundus photographs from a screening population of patients with diabetes can be made with adjustable priority settings, emphasizing high-sensitivity identification of diabetic retinopathy or high-specificity identification of absence of retinopathy, covering opposing extremes of visual evaluation strategies demonstrated by human observers.

Aneurysm↗

PubMed2003

Automated detection of fundus photographic red lesions in diabetic retinopathy.

PURPOSE: To compare a fundus image-analysis algorithm for automated detection of hemorrhages and microaneurysms with visual detection of retinopathy in patients with diabetes. METHODS: Four hundred fundus photographs (35-mm color transparencies) were obtained in 200 eyes of 100 patients with diabetes who were randomly selected from the Welsh Community Diabetic Retinopathy Study. A gold standard reference was defined by classifying each patient as having or not having diabetic retinopathy based on overall visual grading of the digitized transparencies. A single-lesion visual grading was made independently, comprising meticulous outlining of all single lesions in all photographs and used to develop the automated red lesion detection system. A comparison of visual and automated single-lesion detection in replicating the overall visual grading was then performed. RESULTS: Automated red lesion detection demonstrated a specificity of 71.4% and a resulting sensitivity of 96.7% in detecting diabetic retinopathy when applied at a tentative threshold setting for use in diabetic retinopathy screening. The accuracy of 79% could be raised to 85% by adjustment of a single user-supplied parameter determining the balance between the screening priorities, for which a considerable range of options was demonstrated by the receiver-operating characteristic (area under the curve 90.3%). The agreement of automated lesion detection with overall visual grading (0.659) was comparable to the mean agreement of six ophthalmologists (0.648). CONCLUSIONS: Detection of diabetic retinopathy by automated detection of single fundus lesions can be achieved with a performance comparable to that of experienced ophthalmologists. The results warrant further investigation of automated fundus image analysis as a tool for diabetic retinopathy screening.

Algorithms↗

PubMed2003

Evaluation of heredity as a determinant of retinal nerve fiber layer thickness as measured by optical coherence tomography.

PURPOSE: To study to what extent genetic factors determine the retinal nerve fiber layer thickness (RNFLT) in healthy subjects. METHODS: In vivo peripapillary optical coherence tomography (OCT), clinical examination, lens fluorescence, and fundus photography were performed on both eyes of 25 monozygotic and 25 dizygotic same-sex pairs of twins. The cross-sectional study included twins aged from 20 to 45 years recruited from a population-based register. Only healthy eyes were included. MAIN OUTCOME VARIABLES: peripapillary OCT RNFLT, reproducibility, and heritability (the proportion of the total observed variance statistically attributable to genetic factors). RESULTS: The within-pair difference in RNFLT was 4.6% (0.7%-15.2%; median [range]) in monozygotic versus 7.3% (0.2%-20%) in dizygotic twins (P = 0.032, Mann-Whitney test). The RNFLT heritability was 66%. The RNFLT measurement was found to decrease 3.8 microm per decade (P = 0.003). The RNFLT heritability increased to 82%, when corrected for the effect of age and excluding within-pair refractive differences of 2 D or more. The signal-to-noise ratio correlated with lens transmittance (r = 0.25, P = 0.012), age (r = -0.29, P = 0.004), and RNFLT (r = 0.43, P < 0.001). Intravisit RNFLT reproducibility was 4.2%. CONCLUSIONS: Peripapillary RNFLT in healthy adults, as measured by OCT, was determined predominantly by genetic factors in this study population. Theoretically, these factors may involve variations in the number of ganglion cells and nerve fiber formations early in life and/or in the rate at which these structures are subsequently lost.

Adult↗

PubMed2002

Retinal atrophy in idiopathic central serous chorioretinopathy.

PURPOSE: To study retinal atrophy in idiopathic central serous chorioretinopathy (ICSC). DESIGN: Observational case series. METHODS: Twenty-four eyes in 23 consecutive patients aged 33 to 67 years and 50 eyes in 25 healthy volunteers aged 24 to 70 years were studied. Observational procedures included: biomicroscopy, fundus photography, fluorescein angiography, optical coherence tomography, photocoagulation. Retinal thickness after resolution of detachment, definite attenuation being defined as foveal thickness less than the mean -2 SD in healthy volunteers; duration of symptoms; best-corrected visual acuity (BCVA). RESULTS: Definite retinal attenuation, retinal thickness ranging from 51% to 74% of normal, was found in nine eyes of nine patients with idiopathic central serous chorioretinopathy (ICSC). Their duration of symptoms was longer (P =.0014) and their BCVA was lower (P =.015) than eyes in patients with normal-range foveal thickness who, nevertheless, had thinner foveae than healthy subjects (P =.10). The most severe reduction of foveal thickness, to half the normal (three eyes of three patients), was associated with BCVA 0.5 or less, multifocal retinal pigment epithelial abnormalities, and more than 10 years' duration of symptoms. Retinal attenuation was seen only after a duration of symptoms of more than 4 months, being most pronounced in the photoreceptor layer, particularly in the fovea. CONCLUSION: Foveal attenuation in ICSC is associated with more than 4 months' duration of symptoms and persistent BCVA reduction despite resolution of the serous detachment. We found no other likely cause of atrophy than the prolonged absence of contact between photoreceptors and retinal pigment epithelial cells.

Adult↗

PubMed2002

Molecular analysis of KTI12/TOT4, a Saccharomyces cerevisiae gene required for Kluyveromyces lactis zymocin action.

TOT, the putative Kluyveromyces lactis zymocin target complex from Saccharomyces cerevisiae, is encoded by TOT1-7, six loci of which are isoallelic to RNA polymerase II (RNAPII) Elongator genes (ELP1-6). Unlike TOT1-3 (ELP1-3) and TOT5-7 (ELP5, ELP6 and ELP4 respectively), which display zymocin resistance when deleted, TOT4 (KTI12) also renders cells refractory to zymocin when maintained in multicopy or overexpressed from the GAL10 promoter. Elevated TOT4 copy number results in an intermediate tot phenotype, which includes mild sensitivities towards caffeine, Calcofluor white and elevated growth temperature, suggesting that TOT4 influences TOT/Elongator function. Tot4p interacts with Elongator, as shown by co-immunoprecipitation, and cell fractionation studies demonstrate partial co-migration with RNAPII and Elongator. As Elongator subunit interaction is not affected by either deletion of TOT4 or multicopy TOT4, Tot4p may not be a structural Elongator subunit but, rather, may regulate TOT/Elongator in a fashion that requires transient physical contact with TOT/Elongator. Consistent with a regulatory role, the presence of a potential P-loop motif conserved between yeast and human TOT4 homologues suggests capability of ATP or GTP binding and P-loop deletion renders Tot4p biologically inactive.

Adaptor Proteins, Signal Transducing↗

PubMed2002

Time-resolved and steady-state fluorescence spectroscopic studies of the human lens with comparison to argpyrimidine, pentosidine and 3-OH-kynurenine.

The intrinsic fluorescence from the human lens on excitation in the UV region, referred to as blue lens autofluorescence, increases with age or in the presence of diabetes. The present study reveals that the relative contribution of compounds responsible for the blue autofluorescence appears to be a constant with age. Three potential candidates for the blue fluorescence were also studied with respect to fluorescence spectroscopic properties. These were argpyrimidine and pentosidine, both advanced glycation end products, and 3-hydroxykynurenine (3-OH-kynurenine), a photooxidative derivative of tryptophan. It was shown that the spectral properties of argpyrimidine and pentosidine are compatible with the observed blue fluorescence of the human lens, whereas the fluorescence from 3-OH-kynurenine is negligible.

Adult↗

PubMed2002

Diabetic macular edema assessed with optical coherence tomography and stereo fundus photography.

PURPOSE: To compare retinal thickening in diabetic macular edema assessed subjectively by evaluation of stereo fundus photographs with that assessed objectively by optical coherence tomography (OCT). METHODS: Forty-degree stereo fundus photographs of the macular field and OCT scans in 84 eyes of 47 patients with diabetes were compared in terms of both location and area of retinal thickening. Six radiating 6-mm OCT scans at intervals of 30 degrees were obtained, and the retinal thickness was compared with the mean retinal thickness +/- 2 SD of healthy control subjects (33 eyes). Subsequently, retinal thickness was mapped topographically and the subjectively assessed retinal thickening map was overlaid. The degree of agreement on location was evaluated as retinal thickening present or absent in nine subfields of the fundus. Area of retinal thickening was divided into four categories: no retinal thickening, less than 1 disc area (DA), less than 2 DAs, or less than 3 DAs, expressed as the kappa statistic. RESULTS: Exact agreement on location was found in 676 of 756 (84 x 9) observations (89.4%; kappa = 0.69; 95% confidence interval [CI]: 0.63-0.75). Two eyes in which both methods assessed the same amount of retinal thickening showed no agreement on location. These eyes were compared only in terms of location. Exact agreement on area was found in 69 (84.1%) of 82 eyes. Weighted kappa (kappa(w)) = 0.79; 95% CI: 0.76-0.82). CONCLUSIONS: The degree of agreement between subjectively and objectively assessed retinal thickening was very good, implying that changes in diabetic macular edema can be accurately and prospectively measured with OCT.

Adult↗

PubMed1998

Neural classifier construction using regularization, pruning and test error estimation.

In this paper we propose a method for construction of feed-forward neural classifiers based on regularization and adaptive architectures. Using a penalized maximum likelihood scheme, we derive a modified form of the entropic error measure and an algebraic estimate of the test error. In conjunction with optimal brain damage pruning, a test error estimate is used to select the network architecture. The scheme is evaluated on four classification problems.

Journal Article↗

PubMedDate not supplied

Nematophagous fungi as a biological control agent for nematode parasites of small ruminants in Malaysia: a special emphasis on Duddingtonia flagrans.

Approximately 2,800 fresh dung samples from animals, mainly ruminant livestock, were screened for the presence of nematophagous fungi in Malaysia. Arthrobotrys spp. was noted on numerous occasions, but only one isolate of Duddingtonia flagrans was made. For the purposes of producing sufficient quantities of this fungus for feeding trials in sheep, various, commonly available, cheap plant materials were tested as possible growth substrates. This showed that cereal grains (wheat, millet and rice) were the best media for fungal growth. Pen feeding trials were carried out using sheep, both naturally and experimentally infected with nematode parasites (predominantely Haemonchus contortus), to test the efficiency of D. flagrans when administered either in a grain supplement, or incorporated into a feed block. These showed that the fungus survived gut passage in sheep and that dose rates of approximately 1 x 10(6) D. flagrans spores / animal / day, reduced the percentage of infective larvae developing in faecal cultures by more than 90%. These results indicate that using D. flagrans as a biological control agent of nematode parasites, is a promising alternative to nematode parasite control of small ruminants in Malaysia, where anthelmintic resistance is now a major problem.

Animal Feed↗

PubMedDate not supplied

[Biological control of helminths in grazing animals using nematophagous fungi].

For the last 50 years the control of gastro-intestinal nematodes (GIN) in grazing animals has almost entirely been alleviated by the use of anthelmintics. Due to development of resistance against the drugs, especially in the GIN of sheep and goats it has become necessary to develop new, innovative strategies such as the use of nematode destroying fungi. Despite experiments to employ various species against plant and animal parasitic nematodes were already attempted in the 1930's, it was not until the 1990's when selection by simulating passage through the gastro-intestinal tract of cattle led to isolation of the fungus Duddingtonia flagrans that a major breakthrough was achieved. This fungus, producing sticky three-dimensional network and now isolated world-wide, is special due to its capacity to prolifically produce high numbers of thick-walled resting spores, chlamydospores. These spores survive passage through the gastro-intestinal tract of grazing livestock and are capable of growing and subsequently trap nematodes, including larval stages of parasitic nematodes. The great potential of this fungus as a biological control agent has been demonstrated through numerous trials with cattle, sheep, horses, and pigs. But these trials have also pointed towards some potential limitations in the activity spectrum of the fungus (Dictyocaulus, Nematodirus) beside the whole group of parasites spreading through infective stages protected inside resistant eggs (e.g. Ascaris, Trichuris). So far, in the few reported studies conducted, no negative environmental impact has been found, but it is important that further studies are conducted on this important issue. Although the potential use of D. flagrans chlamydospores has been verified through numerous trials it is necessary to develop practical delivery systems such as slow release devices, feed-blocks or similar to be able to implement this tool in future integrated control strategies. Such control strategies could include the use of biological control, grazing management, smart use of existing drugs, parasite resistant animal breeds, bioactive forages, and possibly vaccines.

Animals↗