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Biomedical subjects

B Guy

Publications and source records attributed to B Guy.

At least 19 recordsLinked to original sources
PubMed2003

Continuous insulin infusion in hyperglycaemic very-low-birth-weight infants receiving parenteral nutrition.

Continuous infusion of insulin was used to improve glucose tolerance in 30 premature (26.4+/-1.4 weeks) very-low-birth-weight (750+/-211.3 g) hyperglycaemic infants receiving parenteral nutrition. Infusion of insulin was started at 159.1+/-67 h of life; while glycaemia was 12.1+/-3.3 mmol/l. Normoglycaemia was restored within 31.4h (range 2-134 h). A maximum insulin dose of 0.4 (range 0.07-4.2)IU/kg/h was required to control the blood glucose, the mean cumulative doses of insulin required was 3.27 IU/kg (range 0.09-18.1). The mean glucose infusion rate during insulin treatment was 20.3+/-1.7 g/kg/day; lipid was 4.6+/-1.1 g/kg/day and non-protein caloric intake 121.7+/-16.5 kcal/kg/day. Infants reach 85 kcal/kg/day of non-protein energy intake at 179.5+/-71.2 h after birth. During continuous insulin infusion, enteral feeding was started in all infants at 124.9+/-75.8 h of life. Insulin was continued for 317.7+/-196.6 h. Only two infants lost weight during the first week of treatment, the remaining infant gained weight steadily. In conclusion, continuous insulin infusion can rapidly and safely improve intravenous glucose tolerance, allowing higher caloric intake and growth in very-low-birth-weight infants who develop hyperglycaemia during total parenteral nutrition.

Enteral Nutrition↗
PubMed2001

Design, characterization and preclinical efficacy of a cationic lipid adjuvant for influenza split vaccine.

We prepared a series of cationic lipid vesicles comprising a cationic cholesterol derivative, DC-Chol with or without a neutral phospholipid, DOPC or DOPE. The vesicles were tested for their ability to bind and adjuvant split inactivated influenza vaccines. We found that DC-Chol-containing liposomes are capable to strongly bind influenza vaccine antigens upon simple mixing with the vaccine. The resulting formulations induced robust anti-influenza immune responses both after s.c. and i.n. administration in BALB/c mice while neutral Cholesterol/DOPC liposomes displayed virtually no stable antigen binding and no adjuvant effect. The parenteral adjuvant effect of DC-Chol on trivalent split influenza vaccines was then confirmed in outbred mice and monkeys. Among the most potent formulations tested, a simple mixture of the vaccine with a microfluidized dispersion of DC-Chol in an aqueous buffer is being considered for further development to produce an improved influenza vaccine.

Adjuvants, Immunologic↗
PubMed2001

[Blood transfusion despite early use of erythropoietin: failure or limit of therapy? Annual cohort study of premature infants weighing less than 1500 g].

STUDY: Prospective, observative study. SETTING: Neonatal intensive care unit in a university tertiary care hospital. AIMS: 1) Assessment of blood transfusion requirement. 2) Demonstration of haematocrit and hemoglobin level difference at birth between transfused and non-transfused infants. 3) Assessment of iron mass before and after early iron supplementation. POPULATION: All premature infants without cardiopathy, surgical diseases, hemolysis or haemorrhage, at less than 30 weeks of gestational age or less than 32 weeks, weighing less than 1,500 grams, with respiratory distress syndrome admitted into the unit during the year 1998, were included in the study. Each received erythropoietin (750 U.kg-1.wk-1) with intravenous iron supplements from day 5 (0.017 mmol.kg-1.d-1), then orally (0.17 mmol.kg-1.d-1). RESULTS: Seventy-nine premature infants were included in this study. 1) Sixty-seven percent of the transfusions occurred during the first 14 days of life. 2) Haematocrit and hemoglobin levels at birth were significantly different between transfused and non-transfused infants (P < 0.001) and remained different for infants of less than 28 weeks (P < 0.01). 3) After six weeks of iron supplementation (mean 0.31 mmol/kg), the ferritin level had significantly decreased in the non-transfused (P < 0.001) and transfused population (P < 0.01). CONCLUSION: Increasing the haematocrit and the hemoglobin levels at birth, for example by placentofetal transfusion, could decrease the number of early transfusion. Early intravenous iron supplementation had no side effects but did not maintain iron levels.

Blood Transfusion↗
PubMed2001

Formulations of single or multiple H. pylori antigens with DC Chol adjuvant induce protection by the systemic route in mice. Optimal prophylactic combinations are different from therapeutic ones.

The ability to induce a protective response against Helicobacter pylori infection has been investigated by systemic immunization of mice with urease formulated with the cationic lipid DC Chol. This compound acts both as a formulating agent and as an adjuvant and induces a balanced Th1/Th2 response shown to be more effective for protection in our previous studies. Urease-DC Chol induced a significant protection in prophylaxis but not in therapeutic immunization. The protection level was between 1.5 and 2 log reduction of bacterial density measured by quantitative culture compared to unimmunized-infected mice. In parallel, the protective efficacy of other H. pylori antigens formulated in a similar way and administered with DC Chol was tested. These antigens were tested alone or in combination in prophylactic and therapeutic regimens. Some combinations of antigens induced a better prophylactic or therapeutic activity than urease alone (0.5-1.5 log further reduction in prophylaxis and therapy respectively, P<0.05). The combinations that induced the best protection were different in prophylaxis and therapy. In conclusion, DC Chol provides a convenient and efficient method to formulate different antigens even when they are present in non-compatible buffers initially. Moreover, the results obtained in protection against H. pylori with such formulations should lead the way to future clinical trials.

Adjuvants, Immunologic↗
PubMed2001

Assessment of Helicobacter pylori gene expression within mouse and human gastric mucosae by real-time reverse transcriptase PCR.

Despite increasing knowledge on the biology of Helicobacter pylori, little is known about the expression pattern of its genome during infection. While mouse models of infection have been widely used for the screening of protective antigens, the reliability of the mouse model for gene expression analysis has not been assessed. In an attempt to address this question, we have developed a quantitative reverse transcriptase PCR (RT-PCR) that allowed the detection of minute amounts of mRNA within the gastric mucosa. The expression of four genes, 16S rRNA, ureA (encoding urease A subunit), katA (catalase), and alpA (an adhesin), was monitored during the course of a 6-month infection of mice and in biopsy samples from of 15 infected humans. We found that the selected genes were all expressed within both mouse and human infected mucosae. Moreover, the relative abundance of transcripts was the same (16S rRNA > ureA > katA > alpA), in the two models. Finally, results obtained with the mouse model suggest a negative effect of bacterial burden on the number of transcripts of each gene expressed per CFU (P < 0.05 for 16S rRNA, alpA, and katA). Overall, this study demonstrates that real-time RT-PCR is a powerful tool for the detection and quantification of H. pylori gene expression within the gastric mucosa and strongly indicates that mice experimentally infected with H. pylori provide a valuable model for the analysis of bacterial gene expression during infection.

Animals↗
PubMed2000

Comparison of polymorphonuclear cells from healthy donors and differentiated HL-60 cells as phagocytes in an opsonophagocytic assay using antigen-coated fluorescent beads.

Polymorphonuclear cells (PMNs) from healthy donors and differentiated HL-60 cells were compared in an opsonophagocytic assay using fluorescent latex beads coated with Streptococcus pneumoniae polysaccharide conjugates. Serum-specific phagocytosis was efficiently mediated by both sources of cells, as measured by flow cytometry, but the mean number of beads ingested per cell was three- to fivefold higher when PMNs were used than when HL-60 cells were used. Nevertheless, differentiated HL-60 cells could be a convenient and standardized source of cells to evaluate the functionality of specific antibodies to vaccine candidates as a coating on fluorescent beads.

Animals↗
PubMed2000

Parenteral adjuvant activities of Escherichia coli heat-labile toxin and its B subunit for immunization of mice against gastric Helicobacter pylori infection.

The heat-labile toxin (LT) of Escherichia coli is a potent mucosal adjuvant that has been used to induce protective immunity against Helicobacter felis and Helicobacter pylori infection in mice. We studied whether recombinant LT or its B subunit (LTB) has adjuvant activity in mice when delivered with H. pylori urease antigen via the parenteral route. Mice were immunized subcutaneously or intradermally with urease plus LT, recombinant LTB, or a combination of LT and LTB prior to intragastric challenge with H. pylori. Control mice were immunized orally with urease plus LT, a regimen shown previously to protect against H. pylori gastric infection. Parenteral immunization using either LT or LTB as adjuvant protected mice against H. pylori challenge as effectively as oral immunization and enhanced urease-specific immunoglobulin G (IgG) responses in serum as effectively as aluminum hydroxide adjuvant. LT and LTB had adjuvant activity at subtoxic doses and induced more consistent antibody responses than those observed with oral immunization. A mixture of a low dose of LT and a high dose of LTB stimulated the highest levels of protection and specific IgG in serum. Urease-specific IgG1 and IgG2a antibody subclass responses were stimulated by all immunization regimens tested, but relative levels were dependent on the adjuvant used. Compared to parenteral immunization with urease alone, LT preferentially enhanced IgG1, while LTB or the LT-LTB mixture preferentially enhanced IgG2a. Parenteral immunization using LT or LTB as adjuvant also induced IgA to urease in the saliva of some mice. These results show that LT and LTB stimulate qualitatively different humoral immune responses to urease but are both effective parenteral adjuvants for immunization of mice against H. pylori infection.

Adjuvants, Immunologic↗
PubMed1999

Comparison between targeted and untargeted systemic immunizations with adjuvanted urease to cure Helicobacter pylori infection in mice.

Outbred OF1 mice infected in a first step with a mouse-adapted Helicobacter pylori strain were immunized in a second step by systemic or mucosal routes: systemic immunizations were performed subcutaneously with adjuvanted urease either in the infra or supra-diaphragmatic region of the body, while mucosal immunization was done with urease in the presence of E. coli heat Labile toxin. Mucosal and subcutaneous immunizations induced in infected mice a significant reduction in bacterial density whatever the site of injection but complete eradication was preferentially observed in mice immunized subcutaneously in the back. Systemic immunization with appropriate schedules and formulations could constitute a valuable approach to cure Helicobacter pylori infection.

Adjuvants, Immunologic↗
PubMed1998

Systemic immunization with urease protects mice against Helicobacter pylori infection.

The ability of systemic immunization to induce protection against Helicobacter pylori infection has been evaluated in a mouse model. It was observed that if appropriate formulations and adjuvants were used such immunization elicited in outbred Swiss mice levels of protection similar or better than those induced by the oral route in the presence of cholera toxin or Escherichia coli heat labile toxin. Recombinant urease mixed with adjuvants, which induced strong Th1 and Th2 responses elicited better protection than urease mixed with adjuvants which induced a predominant Th2 type response only. These experiments demonstrate the feasibility of parenteral immunization against H. pylori and suggest that an appropriate balance between Th1 and Th2 type responses is required to achieve complete protection.

Adjuvants, Immunologic↗
PubMed1998

Effects of the nature of adjuvant and site of parenteral immunization on the serum and mucosal immune responses induced by a nasal boost with a vaccine alone.

Outbred OF1 mice were immunized subcutaneously with flu vaccine, either in the neck or in the lumbar region (back), in combination with adjuvants inducing either a Th1- or a Th2-type response, referred to as adjuvants A1 and A2, respectively. After two parenteral immunizations, the mice were boosted intranasally with nonadjuvanted vaccine. The serum response was analyzed after each immunization by measuring specific immunoglobulin A (IgA), IgG1, and IgG2a antibody levels, while the local response (same isotypes) was measured in the salivary glands after the mucosal boost by ELISPOTs. We observed that systemic priming at any of the two sites with a Th2 rather than a Th1 adjuvant dramatically enhanced the mucosal IgG1 and IgA responses following a mucosal boost with unadjuvanted vaccine. In addition, as judged by the IgG2a/IgG1 ratios and serum IgA levels, immunization of mice in the back induced a rise in Th2 response compared to neck immunization with adjuvant A1. In contrast, such back immunization with adjuvant A2 reversed the Th1-Th2 balance in favor of the Th1 response compared to neck immunization. Similar differences were observed in mucosal antibody levels according to the site of priming with one given adjuvant; priming in the back with adjuvant A1 increased the mucosal IgA and IgG1 responses compared to neck priming, while the local IgG2a levels were decreased. The reverse was true for adjuvant A2. Back versus neck priming with this latter adjuvant decreased the mucosal IgG1 response, while local IgG2a levels were increased. The different lymphatic drainages of the two sites of parenteral immunization may explain these differences, due to the targeting of particular lymphoid inductive sites. Some of these sites may represent crossroads between systemic and mucosal immunity.

Adjuvants, Immunologic↗
PubMed1997

OspA lipoprotein of Borrelia burgdorferi is a mucosal immunogen and adjuvant.

The outer surface protein A (OspA) lipoprotein of Borrelia burgdorferi, like cholera toxin and the heat-labile enterotoxin of Escherichia coli, induces pro-inflammatory cytokines. This suggested that, like those toxins, OspA might be a mucosal immunogen and adjuvant. OspA, administered intranasally (i.n.) or intragastrically, induced strong serum IgG and salivary gland IgA responses. The serum IgG isotypes were indicative of a mixed T helper 1 and T helper 2 response, the latter being more pronounced. The N-terminal tripalmitoyl-S-glyceryl-cysteine (Pam3Cys) lipid moiety was absolutely required. OspA strongly enhanced the serum IgG and salivary gland IgA responses to jack bean urease co-administered by the i.n. route. OspA also enhanced the response to tetanus toxoid and induced limited protection against challenge. A synthetic lipopeptide also adjuvanted the response to urease by the i.n. route, but was ca 500-fold less potent on a molar basis than OspA. These results suggest that OspA or other lipoproteins may be useful in mucosal vaccines.

Adjuvants, Immunologic↗
PubMed1995

Analyzing Behavior State and Learning Environments: application in instructional settings.

An evaluation of the effects of the ABLE (Analyzing Behavior State and Learning Environments) model was presented. Eight teachers received training on observing behavior state and relevant environmental variables; analyzing potential effects of nutrition and medications; identifying strategies for individual students; and participating in a process to generate classroom-based intervention strategies based on their observations. Results showed that teachers were able to reliably implement the model, which produced significant increases in occurrences of the preferred alert and active states and significant decreases in nonpreferred states, such as sleep, drowse, daze, and crying/agitated. Additional findings indicated that the teachers were satisfied with the training procedures and found the model to be relevant and appropriate for students with profound mental retardation. Case studies were briefly presented.

Adolescent↗
PubMed1995

Different patterns of HIV-1-specific cytotoxic T-lymphocyte activity after primary infection.

OBJECTIVE: To analyse the HIV-1-specific cytotoxic T-lymphocyte (CTL) responses of nine HIV-seropositive subjects in relation with primary infection. METHODS: Anti-HIV CTL were generated by in vitro stimulation of peripheral mononuclear cells obtained from HIV-seropositive donors at various times after primary infection. They were tested against several structural or regulatory HIV-1 proteins, using autologous target cells infected with recombinant vaccinia viruses expressing one of the HIV-1LAI proteins. RESULTS: An important CTL activity was found during the first month following seroconversion only in those donors who showed clinical symptoms during primary infection. The temporal evolution of this response differed for each subject; one remained a non-responder even 30 months after seroconversion. The structural proteins were recognized particularly early, while the antigenicity of regulatory proteins appeared later. CONCLUSION: Different patterns of HIV-specific CTL response can be observed after primary infection. The evolution of infection in these different HIV-seropositive subjects will be particularly interesting to analyse.

Adult↗
PubMed1994

Adenosine in painful legs and moving toes syndrome.

Painful legs and moving toes is a rare syndrome with controversial physiopathology. We report two cases that were relieved by applying transcutaneous vibratory simulation. The pain relief was objectively evaluated using the nociceptive flexion reflex of the lower limb (RIII reflex). In these patients, we found a deficiency in circulating adenosine levels, which was not found in other chronic painful syndromes (sciatic pain). Based on these observations, we successfully treated patients with painful legs and moving toes by the administration of ATP. The deficit in blood adenosine may be an explanation of the physiopathology of this syndrome.

Adenosine↗
PubMed1994

Some educational implications for students with profound disabilities at risk for inadequate nutrition and the nontherapeutic effects of medication.

The educational relevance for students with profound disabilities of being at risk for poor nutrition and the potential problems caused by the nontherapeutic effects of some medications were examined, examples of their significance presented, some reasons for their occurrence discussed, and some suggestions for instructional personnel offered. Two classroom-based cases were included that described the resolution of a nutritional and a medication problem, including the role of the teacher and health-related personnel.

Child↗
PubMed1993

Gag-specific cytotoxic T lymphocytes from human immunodeficiency virus type 1-infected individuals: Gag epitopes are clustered in three regions of the p24gag protein.

Virus-specific cytotoxic T lymphocytes (CTL) may be an important host defense mechanism in the control of virus replication in persons infected with human immunodeficiency virus type 1 (HIV-1). Cytotoxic T-cell lines generated by nonspecific stimulation with anti-CD3 monoclonal antibodies and interleukin 2 were used to identify regions within the HIV-1 Gag protein that are the most frequently recognized. Using autologous Epstein-Barr virus-transformed target cells infected with recombinant vaccinia viruses encoding p18gag, p24gag, and p55gag proteins of HIV-1/Lai or selected truncations of p24gag, we show that within a group of 29 infected subjects, the p24gag protein is the target of Gag-specific CTL in most donors. Using autologous Epstein-Barr virus-transformed target cells coated with different synthetic peptides spanning the Gag amino acid sequence, we found clusters of partially overlapping peptides in three conserved regions of the p24 protein (amino acids [aa] 169 to 192, aa 219 to 304, and aa 335 to 372) that are frequently recognized by CTL and presented by a variety of human leukocyte antigen class I molecules. Since there are experiments both in vitro and in vivo showing the role of CTL in the control of virus replication in HIV and simian immunodeficiency virus infections, these results may be particularly important for vaccine development.

Amino Acid Sequence↗
PubMed1993

Analysis of behavior state conditions and associated environmental variables among students with profound handicaps.

State conditions in combination with environmental events and factors significantly affect the level of alertness and responsiveness among students with profound and multiple handicaps. State conditions and environmental variables over a continuous, 5-hour period for each of 25 students in classroom settings were measured. Data were assessed using transitional probability, time series, and correspondence analysis procedures. Results showed the presence of state sequence patterns, short state change periods, and a relatively small amount of association between specific behavior states and the environmental factors and events measured in the study.

Adolescent↗