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L L Hansen

Publications and source records attributed to L L Hansen.

At least 73 records · Page 4Linked to original sources

[Do scars grow despite successful laser coagulation of subretinal neovascularization?].

After successful laser coagulation of subretinal neovascularization, we examined 9 patients to see if laser scar growth (which can be expected according to the literature) is accompanied by an increase in associated scotoma. We used a specially designed visual field program. Laser scars had grown by 23% 107 days after therapy and by 32% after 409 days. The changes in our patients were at the lower range of the data reported in the literature. The increase in the laser scar was statistically significant in just one patient. Mean sensitivity and two further parameters for describing visual fields, which we introduced, all hinted at an improvement in the central visual field, although the laser scars had grown. The mean sensitivity increased by 4.9% and 7.5% after 107 and 409 days, respectively.

Adult↗

31P and 13C NMR spectroscopic study of wild type and multidrug resistant Ehrlich ascites tumor cells.

Steady-state 31P NMR spectra of wild type EHR2 Ehrlich ascites tumor cells and multidrug resistant EHR2/DNR+ cells, immobilized in agarose threads, and continuously perfused with medium, showed temperature-dependent differences in the levels of intracellular phosphate metabolites. At 37 degrees C, the EHR2/DNR+ cells contained four times more phosphocreatine (PCr) than the EHR2 cells. At 20 degrees C, the EHR2 cells contained 80% more of phosphodiesters (PDE), the levels of PCr being equal. The quantitative metabolite level data are based on T1 relaxation times data and are normalized for the protein content of the cells. Perfusion of the cells with azide, an inhibitor of mitochondrial respiration, had no effect on the ATP level, and caused no changes in glucose consumption and lactate production. Azide perfusion, combined with glucose depletion, caused rapid drop in the ATP content, which was reestablished after renewed perfusion with glucose. Similarly, perfusion with 2,4-dinitrophenol, an uncoupler of the respiration chain, had no effect on the phosphate metabolites. These results demonstrate that aerobic glycolysis is the main route by which glucose is metabolised under the conditions used (glucose concentration in medium 2 g/L). Rates of uptake and phosphorylation of 2-deoxy-D-glucose were measured by following the formation of intracellular [6-13C]2-deoxy-D-glucose-6-phosphate by 13C NMR; at 37 degrees C the observed rates for EHR2 and EHR2/DNR+ cells were equal, about 10 nmol/(min x mg protein), whereas at 20 degrees C the wild type cells produced the 6-phosphate at an approximately twice the rate found for the resistant cells [about 4 and 2 nmol/(min x mg protein), respectively].(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

[Retinal diseases in AIDS].

Retinal diseases are the most frequent and most important ocular manifestations in AIDS. Electrophysiological changes can already be found in early stages of AIDS without funduscopic lesions and are a sign of damage to the retinal receptors and ganglion cells. HIV retinopathy (cotton-wool spots, retinal hemorrhages, microaneurysms) seldom occurs in the early stages with normal T-helper cell counts, but is present in about 40% of patients with AIDS-related complex and even in 70% of patients with full-blown AIDS. The cause of this microangiopathy is not known, but patients with lower T-helper cell counts of comparable stages more often have signs of HIV retinopathy. Infections of the retina and the choroid are always part of full-blown AIDS and represent the most important ophthalmological problem in AIDS, as these may lead to blindness if not treated. The specific diagnosis mainly relies on the ophthalmoscopic appearance, as antibody studies are of little help in final-stage AIDS patients. The amplification and proof of virus DNA particles by polymerase chain reaction seem to be more promising ways of obtaining an early laboratory diagnosis of viral retinal infections, but an intraocular specimen is required. Most (90-95%) of the retinal infections in AIDS are caused by the cytomegalovirus. In the final stage 11-40% of AIDS patients develop cytomegalovirus retinitis. Without treatment blindness can occur within a few weeks. Intravenous ganciclovir or foscarnet can prevent or postpone blindness in these patients, but the agents have to be given lifelong in a maintenance dose. Foscarnet offers a survival advantage over treatment with ganciclovir, although the patients may not tolerate foscarnet as well as ganciclovir. Another important infection is toxoplasmic retinochoroiditis, whereas acute retinal necrosis/herpes simplex retinitis, myotic and bacterial infections as well as Pneumocystis carinii choroiditis are seldom seen.

AIDS-Related Opportunistic Infections↗

Measurement of basal levels of factor VIIa in hemophilia A and B patients.

Previous results, presented in abstract form, indicate that replacement of thromboplastin with a mixture of phospholipid and truncated soluble tissue factor apoprotein results in a coagulation assay that can directly measure plasma factor VIIa levels without interference from zymogen factor VII (Atherosclerosis Thromb 11:1544a, 1991 [abstr]). We have exploited the specificity and sensitivity of such a factor VIIa specific coagulation assay to directly assess the in vivo relationship of factor VIII and factor IX on the production of factor VIIa levels under nonthrombotic and nonstimulatory conditions. Normal individuals (n = 20) were found to possess an average circulating factor VIIa level corresponding to 4.34 +/- 1.57 ng/mL, or approximately 1% of their total factor VII antigen. Severe factor VIII deficient patients (n = 13) possessed a slightly lower but statistically significant (P less than .01) decrease in their basal factor VIIa levels (2.69 +/- 1.52 ng/mL), corresponding to approximately 60% of that observed in normal individuals. On the other hand, severe factor IX deficient patients (n = 7) were found to possess even lower levels of factor VIIa corresponding to 0.33 +/- 0.15 ng/mL, or less than 10% of that observed in normal individuals. Measurement of total factor VII antigen levels shows that the variation in basal factor VIIa levels stems from differences in the degree of factor VII activation as opposed to differences in factor VII antigen levels. Our present data are consistent with the hypothesis that factor IXa is the principal in vivo activator of factor VII under basal conditions.

Factor VIIa↗

Mutations and polymorphisms in the pyruvate dehydrogenase E1 alpha gene.

We present an update on mutations and polymorphisms in the human X chromosome located pyruvate dehydrogenase E1 alpha gene. A total of 20 different mutations are tabulated. The mutations include deletions, insertions, and point mutations. Certain sequences seem particularly prone to mutation. Most of the mutations are found in exons 10 and 11. Furthermore, four of the mutations are seen in unrelated patients. Little is known about how the mutations affect the structure or function of the pyruvate dehydrogenase complex.

Amino Acid Sequence↗

X-linked pyruvate dehydrogenase E1 alpha subunit deficiency in heterozygous females: variable manifestation of the same mutation.

Three female patients are described with pyruvate dehydrogenase (PDH) deficiency as a result of mutation in the X-linked gene for the E1 alpha subunit of the complex. Two of these patients illustrate typical presentations of PDH E1 alpha deficiency, with severe neurological dysfunction, degenerative changes and developmental anomalies in the brain, together with variable lactic acidosis. The third patient extends the known spectrum of the condition to include mild to moderate mental retardation and seizures in an adult. All three patients have the same mutation in the PDH E1 alpha gene. This mutation, a C-to-T substitution in a CpG dinucleotide in amino acid codon 302 (designated R302C), results in the replacement of arginine by cysteine at this position. The mildly affected adult was the mother of one of the other patient, making this the first described instance of mother-to-daughter transmission of a mutation causing PDH E1 alpha deficiency. The genetic basis of the variable expression of X-linked PDH E1 alpha deficiency in heterozygous females is discussed.

Adolescent↗

Haemorheological parameters in patients with retinal artery occlusion and anterior ischaemic optic neuropathy.

The haemorheological parameters haematocrit (Hct), plasma viscosity (PV), red cell aggregation (RCA), red cell filterability (RCF), apparent whole blood viscosity (WBV), and fibrinogen were measured in 31 patients with retinal artery occlusion (RAO), 25 patients with anterior ischaemic optic neuropathy (AION), and 19 patients with giant cell arteritis (GCA). The patient groups were compared with controls of same age and similar prevalence of cardiovascular risk factors. Patients with RAO and AION have a significantly decreased RCF in comparison with controls. All other parameters showed no differences. Patients with GCA had significantly decreased Hct and RCF and increased PV and fibrinogen. After 2 weeks of systemic treatment with high dose steroids in patients with GCA the plasma viscosity had returned to normal and was even lower than in controls, and the Hct and fibrinogen had reached normal levels.

Adult↗

Diagnosis and management of the acute retinal necrosis syndrome.

The acute retinal necrosis (ARN) syndrome is an increasingly occurring entity characterized by the triad of acute confluent peripheral retinitis with papillitis and anterior-chamber uveitis. We present case reports on four patients (age, 12-65 years) with an ARN syndrome caused by herpes simplex or varicella zoster virus and discuss diagnostic and therapeutic modalities. Immediate antiviral therapy in three patients exhibiting the typical clinical features reduced the intraocular inflammation. However, due to proliferative vitreoretinopathy with peripheral retinal necrosis, vitrectomy with encircling band and silicone oil instillation was necessary in all patients. The suspected diagnosis of an ARN syndrome induced by herpes simplex virus (HSV) was confirmed in one case during the early stage of the disease by the detection of increased levels of HSV-IgA in the vitreous and in another case by the measurement of increased titers of HSV-IgG in the vitreous. For the first time, we found intraocular HSV DNA sequences using the polymerase chain reaction (PCR) in one of these patients. In a fourth patient intraocular varicella zoster virus (VZV) infection was confirmed by the detection of elevated VZV-IgA levels and by positive PCR in the intraocular fluids. Two patients who were diagnosed and treated early retained a visual acuity of 0.4 and 0.5, respectively, whereas in the other two patients, whose diagnosis and therapy were delayed (> 6 weeks), visual acuity was reduced to light perception. We conclude that use of the PCR in the intraocular fluids together with detection of autochthonous antibodies in the vitreous seem to be the most important diagnostic laboratory tools.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Polymorphisms in the human X-linked pyruvate dehydrogenase E1 alpha gene.

Pyruvate dehydrogenase E1 alpha deficiency is an X-chromosome-linked disorder, often with fatal consequences. We have searched for genetically useful polymorphisms in or near this gene. No restriction fragment length polymorphisms were detected using a battery of 36 different restriction enzymes and probing with a full-length cDNA fragment, or two single-copy genomic fragments located within intron 8, and 15 kb 3' of the coding region, respectively. The chemical cleavage method was then applied to the detection of base changes in or near the gene. One polymorphism was found in exon 8 of the coding region. However, no base changes were detected in intron 3 or in the part of intron 8 covered by fragment gB2. Three blocks of microsatellite DNA containing variable numbers of CA-repeats were isolated from the 5' end of the gene and characterized. Length polymorphisms in these microsatellite DNAs were analysed using the polymerase chain reaction. Although the three loci are tightly linked, the polymorphisms appear not to be in disequilibrium, making them useful markers in linkage studies of the pyruvate dehydrogenase E1 alpha gene. Of 31 females analysed 12(39%) were heterozygous for at least one length polymorphism of the three (CA)n alleles.

Autoradiography↗

Characterization of the mutations in three patients with pyruvate dehydrogenase E1 alpha deficiency.

The human pyruvate dehydrogenase complex catalyses the oxidative decarboxylation of pyruvate to acetyl-CoA. Defects in several of the seven subunits have been reported, but the majority of mutations affect the E1 component and especially the E1 alpha subunit. However, the clinical presentation of patients with pyruvate dehydrogenase E1 alpha deficiency is extremely variable. Dependency of the brain on pyruvate dehydrogenase activity and localization of the gene for the somatic form of the pyruvate dehydrogenase E1 alpha subunit to the X chromosome provide the basis for a better understanding of the variation in the clinical manifestations. Further understanding of the function and interaction of subunits and the pathophysiology of pyruvate dehydrogenase deficiency necessitates the characterization of mutations in the pyruvate dehydrogenase complex. We report the analysis of three patients with pyruvate dehydrogenase E1 alpha deficiency. One female has a three base pair deletion which affects dephosphorylation of the subunit. Of two males analysed, one has a two base pair deletion causing a shift in the reading frame. The other has a base change, resulting in an Arg to His substitution. All three mutations are located near the carboxyl terminus of the subunit.

Amino Acid Sequence↗

Competition ELISA using a human monoclonal antibody for detection of antibodies against human immunodeficiency virus type 1.

A novel competition ELISA for detection of antibodies against HIV-1 was developed. The assay is based on competition at the single epitope level and utilises a human monoclonal antibody and an E. coli-produced fragment of the transmembrane glycoprotein gp41. The sensitivity of the assay was 100% in tests on 247 serum samples obtained from 219 individuals previously shown to be HIV-1 antibody positive by both conventional indirect ELISA and the immunoblotting test. The patients represented various clinical and immunological stages of HIV-1 infection. Likewise, the specificity of the assay was 100% in tests on 105 serum samples from normal individuals previously tested negative by indirect ELISA. Further, among 105 serum samples selected due to consistent false positive reactions in the indirect ELISA only 2 samples (1.9%) demonstrated false positive reactions in the competition ELISA, i.e. 98.1% specificity. Finally, only 2 of 57 (3.5%) serum samples from HIV-2 infected individuals showed positive reactions in the assay, while 54 (94.7%) had absorbance values similar to the negative controls. These results demonstrate that human monoclonal antibodies may form the basis for highly sensitive and specific assays for detection of antibodies to HIV-1.

AIDS Serodiagnosis↗

[Sudden blindness in an AIDS patient. Simultaneous infection with cytomegalovirus and herpes simplex viruses and development of malignant non-Hodgkin lymphoma].

A 50 year old patient with non-diagnosed HIV-infection at onset of his illness developed impairment of vision and temporary double vision combined with severe hemianopsia. With normal fundus and suspicious Herpes simplex iritis therapy with Acyclovir was started. Primarily the patient showed a good response to the therapy and loss of vision could be prevented. After 4 weeks CMV-retinitis developed. In spite of Gancyclovir therapy manifestation of total loss of vision after 6 weeks. Autopsy demonstrated signs of simultaneous a CMV-infection of the retina and a herpes simplex-infection of the optic nerve combined with a Non-Hodgkin-Lymphoma of the optic tract.

Acquired Immunodeficiency Syndrome↗

[Automatic perimetry of the central visual field in diseases of the macula].

We developed a program for testing the central 12 degrees of the visual field with a spatial resolution of 1.6 degrees that was easy to operate. The program was designed for the Octopus computer-perimeter and created by means of the SARGON-utility. Our way of examining differed slightly from the standard Octopus procedure. We tested 16 normal eyes and 13 eyes of patients with various diseases of the central retina. Our normal values of differential threshold sensitivities were about 1.8 dB below the normal values of the Octopus system. Sensitivity and specificity of the program were nearly identical irrespective of using our normal values or the Octopus normal values for the calculation of the above mentioned parameters. Sensitivity was 84.6%, specificity 87.5%. The ability of the program to correctly localize retinal defects was shown. The program was designed for follow-up of patients having undergone paramacular lasercoagulation.

Adult↗

[Chronic subgaleal abscess as a cause of eyelid swelling].

A 36 year-old female patient presented with a massive swelling of the eyelid, cheek, and neck. We could not explore any cause for those swellings. Finally, magnetic resonance imaging of the head showed a hugh subgaleal abscess. It was caused by minor scalp trauma.

Abscess↗

[Isovolemic hemodilution on non-arteritic anterior optic neuropathy. Initial results of a randomized study].

As there is no generally accepted treatment for non-inflammatory anterior ischemic optic neuropathy, we have started a randomized, controlled clinical trial on isovolemic hemodilution. In this study all patients received a basic treatment of 75 mg of acetylsalicyclic acid daily. Patients were then randomly assigned to either a group without additional therapy or a group with isovolemic hemodilution. Isovolemic hemodilution was carried out over 6 weeks by several blood-letting procedures and replacement of volume by infusion of hydroxyethyl starch solutions (PCV down to 35-32%). So far, 21 patients have fulfilled the inclusion criteria (symptoms less than or equal to 30 days, no medical contraindications, no giant-cell arteritis), and since they matched for age, duration of symptoms, cardiovascular risk factors, they could be observed for at least 3 months. Although only 1 of 10 control patients hat better visual acuity after 3 months; 6 out of 11 hemodiluted patients had better vision after treatment (p = 0.024). These results indicate that isovolemic hemodilution most likely has a beneficial effect on the visual prognosis of patients with anterior ischemic neuropathy.

Aged↗

Deuterium D(V/K) isotope effects on ethanol oxidation in hepatocytes: importance of the reverse ADH-reaction.

The kinetic deuterium isotope effect, D(V/K), on ethanol oxidation was measured on hepatocytes from rat and pig by the radiometric competitive method using 14C-labelled ethanol containing deuterium in the (1-R)-position. The corrected D(V/K) values of 2.68 and 2.80 for rat and pig hepatocytes respectively were significantly different, suggesting differences in the amount of non-ADH ethanol oxidizing activity. The apparent isotope effects declined rapidly with time when acetaldehyde was present in the medium as a result of the reduction to ethanol of the [14C]-acetaldehyde formed from the double labelled ethanol by alcohol dehydrogenase (ADH). Fructose and cyanamide caused the acetaldehyde concentration during ethanol oxidation to increase by entirely different mechanisms, and the isotope effect to decrease with time, as did also the addition of acetaldehyde. The apparent first order rate constant for the reverse ADH reaction, assuming the reactants to be acetaldehyde and the ADH-NADH complex, was determined by two methods giving comparable results. In the presence of semicarbazide, which removes acetaldehyde, the isotope effect was nearly constant. This was the case also when the acetaldehyde concentration was very low (less than 1 microM) for other reasons, as in hepatocytes from starved animals. A mathematical formula describing the expected decrease of the apparent isotope effect with time was derived. The different response of pig and rat hepatocytes to addition of fructose (the 'fructose effect') is suggested to be caused by differences in activity of aldehyde dehydrogenases in the two species.

Acetaldehyde↗

Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies: peripheral glycosylation of HIV envelope glycoprotein gp120 may be a target for virus neutralization.

Carbohydrate structures are often involved in the initial adhesion of pathogens to target cells. In the present study, a panel of anticarbohydrate monoclonal antibodies (MAbs) was tested for their ability to inhibit in vitro human immunodeficiency virus infectivity. MAbs against three different N- and O-linked carbohydrate epitopes (LeY, A1, and sialyl-Tn) were able to block infection by cell-free virus as well as inhibit syncytium formation. Inhibition of virus infectivity was independent of virus strain (HTLVIIIB or patient isolate SSI-002), the cell line used for virus propagation (H9 or MT4), and the cell type used as the infection target (MT4, PMC, or selected T4 lymphocytes). Inhibition was observed when viruses were preincubated with MAbs but not when cells were preincubated with MAbs before inoculation, and the MAbs were shown to precipitate 125I-labeled gp120. The MAbs therefore define carbohydrate structures expressed by the viral envelope glycoprotein gp120, indicating that glycans of the viral envelope are possible targets for immunotherapy or vaccine development or both.

Antibodies, Monoclonal↗