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Biomedical subjects

R Reber

Publications and source records attributed to R Reber.

11 recordsLinked to original sources

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant.

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.

Adjuvants, Immunologic↗

Effects of perceptual fluency on judgments of truth.

Statements of the form "Osorno is in Chile" were presented in colors that made them easy or difficult to read against a white background and participants judged the truth of the statement. Moderately visible statements were judged as true at chance level, whereas highly visible statements were judged as true significantly above chance level. We conclude that perceptual fluency affects judgments of truth.

Association↗

[Current drugs for the treatment of tropical malaria].

The occurrence in the early 60's of stable resistance to chloroquine among Plasmodium falciparum strains in the Amazonas and on the Thai-Cambodian border has been a shock for all malariologists. This led to the search for new antimalarials without cross resistance with chloroquine. For each new drug, one of the major concerns was to define how rapidly parasites would develop resistance to this compound. Drug combinations were taken into consideration so as to achieve a delay in the appearance of resistance. The decision to test a triple combination has led to the development of Fansimef, a fixed combination with tablets containing 250 mg mefloquine, 500 mg sulfadoxine and 25 mg pyrimethamine. A very relevant delay in the development of resistance was found both in-vivo--in the P. berghei model--and in-vitro using P. falciparum. Fansimef has also been under investigations for malaria. Controlled clinical trials were performed in Africa, South America and South East Asia. The documentation for this new indication will be submitted to registration authorities in 1991. A preference alternative to continuous chemoprophylaxis is stand-by malaria treatment for travellers to regions where the malaria risk is relatively low. Stand-by treatment is under investigations in France and in Switzerland. In the search for alternative remedies against drug resistant P. falciparum malaria our attention was directed to Yingzhaosu, a new sesquiterpene peroxide of plant origin from traditional Chinese medicine. A short and convenient synthesis of this ring system gave access to a variety of structural analogues of Yingzhaosu.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A prospective study of acute central retinal artery obstruction. The incidence of secondary ocular neovascularization.

We conducted a prospective study to determine the incidence of ocular neo-vascularization following acute central retinal artery obstruction. Only patients initially evaluated within 7 days of visual loss were eligible. Any patient with pre-existing ocular neovascularization or clinical evidence of the ocular ischemic syndrome noted at the initial evaluation was excluded. During the 18-month study, 33 consecutive patients were enrolled. Six patients subsequently developed neovascularization of the iris, an incidence of 18.2%. In these six patients, neovascularization of the iris appeared as early as 12 days to as late as 15 weeks following the artery obstructions. Five of the six patients (15.2% of the total) later developed neovascular glaucoma. Another patient in this series developed neovascularization of the optic disc without neovascularization of the iris, an incidence of 3.0%. Only two of the seven patients with ocular neovascularization had ipsilateral hemodynamically significant carotid artery disease as determined by noninvasive carotid artery testing. This study confirms results of previous retrospective studies that the incidence of ocular neovascularization after central retinal artery obstruction is higher than commonly thought. It also shows that, in the majority of cases, carotid artery disease is not responsible for the neovascularization seen after central retinal artery obstruction.

Acute Disease↗

Retinal tolerance of an implantable light source for use during vitrectomy surgery.

To assess for the possible development of a phototoxic lesion, we exposed five Dutch belted rabbit retinas to constant illumination with an implantable "chandelier" light source at maximal intensity for 1 hour. No clinically apparent lesion developed in any of the experimentally treated eyes by 48 to 72 hours posttreatment. Light and electron microscopic examination failed to reveal any of the characteristic changes of retinal phototoxicity. A control eye treated with a 20-minute exposure to a standard endoiluminator probe at maximal intensity held 2 mm from the retinal surface demonstrated typical light and electron microscopic phototoxic abnormalities, whereas a retina similarly treated with a 5-minute exposure was normal. We have confirmed that a standard endoilluminator probe can create a phototoxic lesion in the experimental setting. Furthermore, no phototoxicity from the sustained retinal exposure to a fixed, implantable light source for a clinically relevant duration could be demonstrated.

Animals↗

Cloned antigens from Plasmodium falciparum as malaria vaccine candidates.

The problems of genetic polymorphism and poor immunogenicity of malaria vaccine candidates are discussed, with emphasis on the Circumsporozoite (CS) and p190 proteins of Plasmodium falciparum. It may be possible to use conserved regions of these proteins to raise protective immune responses against non-polymorphic determinants. Better adjuvants or delivery systems will be a critical factor in development of an effective vaccine.

Amino Acid Sequence↗

Asymmetric proliferative diabetic retinopathy and carotid artery disease.

The authors prospectively evaluated 387 consecutive patients with proliferative diabetic retinopathy (PDR) for asymmetry in posterior segment neovascularization and its relationship to carotid artery disease. For the purpose of this study, asymmetry is defined as the presence of PDR with high-risk characteristics (as per the Diabetic Retinopathy Study) in one eye, with neither proliferative nor preproliferative changes in the opposite eye. Over the 2-year time period of the study, 20 (5.2%) of 387 patients manifested asymmetric PDR by this definition. All 20 patients underwent carotid artery noninvasive testing and 4 (20%) were found to have hemodynamically significant carotid artery disease. Two of the four patients had their proliferative retinopathy ipsilateral to their severe carotid artery stenosis. This finding does not support the hypothesis that a hemodynamically significant carotid artery stenosis protects against the development of PDR.

Adolescent↗

An unusual presentation of branch retinal artery obstruction in association with ocular neovascularization.

A 61-year-old woman presented with a superior papillary branch artery obstruction occurring secondary to an intra-arterial embolus. Thirteen months later she developed neovascularization of the optic disc and retina in the same eye. Although the situation is unusual, this case suggests that retinal branch artery obstruction may rarely predispose to ocular neovascularization.

Carotid Arteries↗