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Biomedical subjects

G Page

Publications and source records attributed to G Page.

At least 37 records · Page 2Linked to original sources
PubMed1999

Malignant trophoblastic disease following a twin pregnancy consisting of a complete hydatiform mole and a normal fetus and placenta. A case report.

We report an unusual pregnancy with a complete hydatiform mole coexisting with a normal fetus and placenta. This report stresses the importance of a correct diagnosis and the dilemmas the clinician is faced with when managing such a case. Malignant trophoblastic disease occurs in 55% of complete hydatiform mole and fetus. Two-thirds require combination chemotherapy.

Abortifacient Agents, Nonsteroidal↗
PubMed1998

Membrane carbohydrate conjugates desialylation does not alter [3H]-dopamine uptake in rat striatal slices.

Incubation of rat striatal slices induced a large decrease (about 50%) of DA uptake and a slight desialylation of polysialogangliosides (GT1b, GD1b, GD1a) with an increase of monosialogangliosides (GM1). Moreover, a pretreatment of slices by exogenous added neuraminidase of Vibrio cholerae did not modify DA uptake, although the pattern of gangliosides was modified and there was considerable loss (about 45%) of sialic acid in gangliosides and glycoproteins. It was verified that neuraminidase activity occured in synaptic membrane. Thus, DA uptake was apparently not altered by desialylation of plasma membrane carbohydrate conjugates.

Animals↗
PubMed1998

Possible relationship between changes in [3H]DA uptake and autoxidation in rat striatal slices.

Many recent studies have suggested that oxidative damage is an important factor in several neurodegenerative disorders. Our investigations considered whether autoxidation of rat striatal slices modified dopamine uptake. Biochemical assays (TBARS, MDA-TBA complex, aldehydes, and fluorescent lipid-soluble products) and a [3H]DA uptake assay were performed on nonincubated striatal slices and on slices incubated for 150 min at 37 degreesC in Krebs-Ringer buffer without addition of free-radical generators. The results showed that spontaneous lipid peroxidation occured during incubation and that DA uptake kinetic was biphasic (high-affinity uptake1 and low-affinity uptake2) with a significant decrease of maximal velocity of uptake. Ascorbate, a known antioxidant, was used to determine whether a relationship existed between lipid peroxidation and reduced dopamine uptake. Addition of ascorbate (100 and 500 microM) in Krebs-Ringer buffer for 150 min at 37 degreesC failed to indicate whether decreased [3H]DA uptake resulted from lipid peroxidation. In fact, ascorbate acted as a prooxidant, only preventing decreased DA uptake2 at 100 microM. Trolox, another antioxidant, inhibited lipid peroxidation by about 95% with a concentration of 700 microM and protected only uptake1. With a concentration of 5000 microM, Trolox also protected uptake2. On the whole, these results indicate that spontaneous autoxidation in rat striatal slices was associated with a lipid peroxidation process that altered the DA uptake system.

Animals↗
PubMed1998

Inhibitory effects of ascorbic acid on dopamine uptake by rat striatal synaptosomes: relationship to lipid peroxidation and oxidation of protein sulfhydryl groups.

Ascorbic acid is frequently added in the incubation medium to prevent oxidation of dopamine (DA) during uptake assays. However, a preliminary study showed that the presence of ascorbic acid induced a decrease of DA uptake after prolonged incubation. The purpose of this study was to determine the mechanism underlying ascorbic acid-induced alterations of DA uptake in rat striatal synaptosomes. In this context, the effects of physiological concentrations of ascorbic acid (100-500 microM) on DA uptake and Na+/K+ ATPase activity (which is essential for DA transporter function) were assessed in synaptosomes before and after incubation at 37 degrees C. The capacity of synaptosomes to take up DA was significantly decreased after incubation owing to a reduction in DA transporters (but with no modification of their affinity for DA). This partial inhibition was associated with a decrease of Na+/K+ ATPase activity, a production of thiobarbituric acid reactive substances (TBARS) and malonaldehyde (MDA), and a loss of sulfhydryl group content. Addition of Trolox C to the medium prevented the reduction of DA uptake, the inhibition of Na+/K+ ATPase activity, the decrease in sulfhydryl group content and the production of TBARS and MDA. These results suggest that ascorbic acid in the presence of contaminant ferrous ions induced a decrease in functional DA transporters, probably through a lipid peroxidation process involving oxidation of sulfhydryl groups and at least in part through a decrease of Na+/K+ ATPase activity.

Animals↗
PubMed1998

Characterization of both dopamine uptake systems in rat striatal slices by specific pharmacological tools.

Previous results have shown that modifications of dopamine (DA) high-affinity uptake1 and those of DA low-affinity uptake2 in rat striatal slices were different after autoxidation of this model and in the presence of antioxidants. The aim of this study was to determine whether these two DA uptake systems correspond to two different dopamine transporters or rather to a single one. A lesion into the substantia nigra of animals by injection of 6-hydroxydopamine, a neurotoxic substance of nigrostriatal dopaminergic neurons led to the suppression of both DA uptake systems. These two DA uptake systems were not modified when animals were treated by reserpine or tetrabenazine, which inhibit the vesicular monoamine transporter. Moreover, they were sodium- and temperature-dependent. Experiments with specific inhibitors showed that 1-[2-(diphenylmethoxy) ethyl]-4-(3-phenylpropyl)-piperazine dihydrochloride (GBR-12935) and (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-tolyl ) nortropane chloride (PE2I), two selective DA uptake inhibitors, were significantly more potent than fluoxetine and nisoxetine (selective serotonin and norepinephrine uptake inhibitors respectively) in both DA uptake systems. However, the concentrations of these products inhibiting low-affinity uptake2 by 50% were much greater than those for high-affinity uptake1. Our data indicate that both DA uptake systems are neuronal, independent of the vesicular monoamine transporter, active and specific for dopamine. Our results suggest that high-affinity uptake1 and low-affinity uptake2 correspond to the same dopamine transporter, but would be situated at different levels in the striatal slice model. Uptake1 could take place at the periphery of the slice whereas uptake2 in the depth of the slice.

Animals↗
PubMed1998

Virus inactivation by solvent/detergent treatment and the manufacture of SD-plasma.

Solvent/Detergent (SD) is an extraordinarily effective means for eliminating enveloped viruses from plasma and plasma products. The safety margin suggested by the rapid and complete kill of enveloped viruses observed in the laboratory has been confirmed repeatedly by groups worldwide and by thirteen years of routine clinical use encompassing an estimated 35 million doses of a wide variety of products. Throughout this time, there has not been a single documented case of enveloped virus transmission by an SD-treated product. This record of safety spawned the development of SD-treated plasma as a substitute for fresh frozen plasma (FFP) and has encouraged the adoption of SD for the treatment of non-blood products such as monoclonal antibodies and those derived from recombinant DNA procedures. This review summarizes the use of SD treatment, including its use in combination with other viral elimination procedures, and also summarizes Vitex's initial experience in the manufacture of SD-Plasma, recently licensed by the U.S. FDA.

Blood-Borne Pathogens↗
PubMed1998

Autoxidation of rat brain homogenate: evidence for spontaneous lipid peroxidation. Comparison with the characteristics of Fe2+- and ascorbic acid-stimulated lipid peroxidation.

Aerobically-incubated brain homogenates are known to undergo autoxidation characterized by spontaneous TBARS production, presumably as a result of lipid peroxidation. However, TBARS measurement alone, because of its lack of specificity, is not sufficient to demonstrate the occurrence of lipid peroxidation in complex biological systems. This study, undertaken to determine whether or not spontaneous oxidation of rat brain homogenate is due to lipid peroxidation, measured different specific markers of this process (fatty acids, lipid aldehydes and the formation of fluorescence products) and studied changes in alpha-tocopherol. Incubation of rat brain homogenates at 37 degrees C under air led to spontaneous TBARS formation, which was accompanied by lipid aldehydes and lipid fluorescence products as well as polyunsaturated fatty acid (PUFA) degradation. Alpha-tocopherol was also consumed. On the whole, these results demonstrate that autoxidation of brain homogenate is a spontaneous lipid peroxidation process. When homogenates were exposed to Fe2+ and ascorbic acid-induced oxidative stress, lipid peroxidation was enhanced. However, spontaneous and stimulated peroxidation showed similar patterns not characteristic of classical lipid peroxidation, i.e. without the lag and accelerating phases typical of a propagating chain reaction. PUFA degradation was limited despite stimulation of peroxidation.

Animals↗
PubMed1998

The suspected scaphoid fracture. How useful is a unit policy?

The records of 196 patients presenting with a clinical suspicion of scaphoid injury were reviewed to evaluate how junior accident and emergency doctors in a teaching hospital managed these patients. The management that was provided was assessed, and it was ascertained whether the presence of a unit policy meant that accident and emergency junior trainees managed patients accordingly. We found that 82% of patients were immobilized for 2 to 13 weeks, with 60 patients (37%) being immobilized for 6 weeks or more. Of the 196 patients presenting with clinical suspicion of scaphoid fracture, a definite scaphoid fracture was found in only 12%. Less than half of the patients (46%) were reviewed by senior accident and emergency doctors or by senior orthopaedic surgeons. Despite the presence of a unit policy, patients were being immobilized for prolonged periods in the absence of a radiographically evident scaphoid fracture. Advice from more experienced members of the staff was not being sought in dubious cases.

Carpal Bones↗
PubMed1997

MPTP toxicity in rat striatal slices: dopamine uptake alteration does not appear to be related to lipid peroxidation.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is used to create experimental models of parkinsonism, induces both dopaminergic neurotoxicity and peroxidation reactions. The present work investigated the interaction between the dopamine (DA) uptake system, lipid peroxidation and MPTP in a rat striatum slice model. [3H]DA uptake was decreased and the concentration of thiobarbituric acid reactive substances (TBARS) increased after a plain preincubation in Krebs-Ringer bicarbonate buffer for 150 min. The decrease in [3H]DA uptake and the increase in TBARS were suppressed by the iron-chelating agent desferrioxamine. Inhibition of [3H]DA uptake was intensified, [3H]GBR 12 935 binding to DA uptake sites was decreased and TBARS production was inhibited in slices after preincubation with MPTP. MPTP effects were inhibited by L-deprenyl, a MAO-B inhibitor. These results suggest that the spontaneous decrease in DA uptake during simple preincubation in pure Krebs-Ringer solution was related to spontaneous TBARS generation. During MPTP preincubation, alteration of the DA uptake mechanism was not due to additional lipid peroxidation since TBARS production was decreased. MPTP effects could have resulted from other events which are discussed.

Animals↗
PubMed1996

Complex regulation of the DNA-binding activity of p53 by phosphorylation: differential effects of individual phosphorylation sites on the interaction with different binding motifs.

The tumor suppressor protein p53 exists in different phosphorylation states depending on the cellular environment and perhaps the stage of the cell cycle. These different phosphorylation states can be mimicked in the baculovirus expression system by employing the phosphatase inhibitor okadaic acid. Hyperphosphorylation of p53, particularly of Ser313 and/or Ser309, stimulated its DNA binding activity (Fuchs, Hecker and Scheidtmann, Eur. J. Biochem. 228, 625, 1995). Here we show that hyperphosphorylation of p53 has different effects on its DNA-binding activity, depending on the phosphorylation sites and the binding motif: (i) Phosphorylation of amino-terminal sites appeared to reduce binding to the RGC consensus motif, whereas additional phosphorylation of both, Ser313 and Ser309 led to enhanced binding. (ii) Upon hyperphosphorylation, binding to the RGC motif was enhanced whereas binding to the p53 response element of the bax1 gene promoter was diminished. (iii) DNA binding was also greatly enhanced by antibodies Pab 122 and 421 directed against the carboxyl terminus, but this latter effect was superimposed by the phosphorylation state of p53. Thus, the DNA binding activity of p53 appears to be regulated in a complex way in that (i) binding to a given sequence motif may be regulated by differential phosphorylation and/or by interaction with other factors; (ii) binding to different motifs may be modulated in opposite ways. Thus, the different genes that are regulated by p53 may be differently affected by these parameters.

Animals↗
PubMed1996

HLA-DR4 may determine expression of actinic prurigo in British patients.

Human leukocyte antigen (HLA) associations have been reported in Amerindian patients with actinic prurigo. To determine if similar associations are present in the British Caucasoid population with actinic prurigo, 26 patients underwent serological typing for HLC Class I and II antigens. DNA analysis by both sequence-specific priming and group-specific amplification with single-stranded oligonucleotide probe hybridization was used to confirm the DR and DQ typing and to perform DR4 subtyping. All patients were DR4 positive, and 25 of 26 patients were DQ7 positive. DR4 subtyping revealed 12 of 20 patients tested to be DRB1*0407. A nonsignificant association was also found with HLA B55 that is in linkage disequilibrium with DRB1*0407. No HLA associations were found in 25 British Caucasoid patients with polymorphic light eruption. DRB1*0407 is rare in European Caucasoids without actinic prurigo, and HLA-DR4 may have an important role in determining expression of this disease.

Adolescent↗
PubMed1995

The Medical Council of Canada's key features project: a more valid written examination of clinical decision-making skills.

In 1986 the Medical Council of Canada (MCC) commissioned a six-year research and development project to create a new, more valid written examination of clinical decision-making skills for the Canadian Qualifying Examination in Medicine. At that time, the qualifying examination consisted of three booklets of multiple-choice questions and one booklet of patient management problems administered over a two-day period. All graduates of Canadian and foreign medical schools must pass this examination before practicing medicine anywhere in Canada except Québec. The project was undertaken because (1) numerous studies do not support the use of patient management problems (PMPs) to assess clinical decision-making skills, and (2) research results on the characteristics of clinical decision-making skills offered guidance to develop new approaches to their assessment. In particular, research suggested that these skills are specific to the case or problem encountered and are contingent on the effective manipulation of a few elements of the problem that are crucial to its successful resolution--the problem's key features. The problems developed by this project focused only on the assessment of these key features. The project was implemented in three overlapping phases over a six-year period, 1986-1992, each containing a development component followed by a pilot test through which the research studies were carried out. The pilot tests were conducted by presenting sets of new key feature problems to classes of graduating students in medical schools across Canada.(ABSTRACT TRUNCATED AT 250 WORDS)

Canada↗
PubMed1995

Developing key-feature problems and examinations to assess clinical decision-making skills.

This article introduces the concept of a key feature and describes its function as the cornerstone of key-feature problems, a new problem format for the written assessment of clinical decision-making skills of medical trainees and practitioners. The rationale for using this problem format and the steps in problem and examination development--including issues of scoring and standard setting--are described. A key feature is defined as a critical step in the resolution of a clinical problem, and a key-feature problem consists of a clinical case scenario followed by questions that focus on only those critical steps. The questions can be presented to require examinees either to write in their responses or to select them from a list of options. For each question, examines can be instructed to supply or select whatever number of responses is appropriate to the clinical task being tested, and answer keys can comprise one or several responses. This problem format, with its focus on only the critical steps in problem resolution, and with its flexibility in question format and scoring keys, effectively addresses the psychometric considerations of content validity and test score reliability, and accommodates the complexity and configurations of actions often required in the resolution of clinical problems.

Clinical Competence↗
PubMed1995

Content validation of key features on a national examination of clinical decision-making skills.

Key features (KFs) represent the critical, or essential, steps in the identification and management of a clinical problem. KFs for 59 clinical problems were defined by members of a test committee for the Medical Council of Canada as part of their efforts to create a more valid written examination of clinical decision-making skills for the Canadian Qualifying Examination in Medicine. In order to evaluate the content validity of KFs that the test committee had defined for the examination, 99 physicians from outside the committee, who came from clerkship programs at all 16 of Canada's medical schools, participated in three studies conducted in 1991. The first study was retrospective and was designed to find the degree of agreement or disagreement that the outside physicians had with the KFs already defined for each problem by the committee members. The second study was prospective and was to compare the KFs generated de novo by the participants with those already defined by the committee members. The third study was to gather the outside physicians' opinions of the frequencies with which graduating students in Canada are exposed to the 59 problems used in the retrospective and prospective studies. Almost all the KFs defined by the test committee were corroborated by the outside physicians, 92% in the retrospective study and 94% in the prospective one.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Comparing times and performances of French- and English-speaking candidates taking a national examination of clinical decision-making skills.

French-speaking candidates taking the translated version of the Medical Council of Canada's (MCC's) Qualifying Examination in Medicine often complain that poor performance could be due to translation defects. The purposes of this 1991 study were to determine (1) whether French-speaking candidates spend the same time as do English-speaking candidates in answering the questions in the fourth and last booklet of Part 1 of the MCC's Qualifying Exam, and (2) for items where the French-speaking candidates have more difficulty, whether these differences are within normal limits, and if not, could they be attributed to faults in the translation? Two versions of the fourth booklet, one in English and the other a translation into French, were administered to 229 randomly selected candidates (98 French speakers and 131 English speakers). The booklets contained 19 clinical problems and a total of 44 key features; performance was measured by the number of key features the examinees correctly responded to. (Key features are the critical or essential steps needed to resolve a clinical problem.) The French text was 16% longer, and the French candidates took longer to complete the two-hour examination (a mean of 116.31 minutes versus 107.84 minutes for the English speakers, p = .000). However, there was no direct relationship between the time spent on a section of the examination and the number of words it contained. The French candidates' overall scores did not differ from those of the English candidates (59.76% versus 61.33%, p = .11).(ABSTRACT TRUNCATED AT 250 WORDS)

Canada↗