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Biomedical subjects

E Pines

Publications and source records attributed to E Pines.

At least 19 recordsLinked to original sources
PubMed2000

A new model for experimental tendon adhesions in the chicken.

A minimally invasive model using a manual abrader to induce adhesions in the chicken's central digit is described. The flexor synovial sheath and the profundus tendon were abraded with access through small flaps at the level of the proximal and distal phalanges of the avian long toes. The birds were divided into two groups according to the severity of the induced trauma. Group I birds received an abrasion injury and were euthanized to allow biomechanical testing 5 weeks postoperatively. Group II birds had a more severe abrasion and were euthanized similarly and tested 5 weeks after surgery. Results were compared with nonsurgical controls. Long toe function was evaluated weekly by measuring (1) the range of active flexion of each interphalangeal joint, resolved to total angular range; (2) the grasping ability on graded-diameter perches; and (3) the flexion deficit of the long toe. Postmortem biomechanical properties of the adhesions were measured. There was a significant difference between the unoperated controls and abraded digits of both groups in all parameters (p < 0.001). There was, in addition, a marked change in most of the measured parameters between groups I and II. In group I digits the functional and biomechanical deficit was less than group II. In summary, this animal model of long-segment abrasive injury to the tendon and sheath is a simple and reproducible method to generate adhesions and can be used for the evaluation of treatment modalities for adhesion prevention.

Animals↗
PubMed2000

Immunogenicity and safety of a new liquid hexavalent combined vaccine compared with separate administration of reference licensed vaccines in infants.

OBJECTIVE: The immunogenicity and safety of a new liquid hexavalent vaccine (diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-hepatitis B-polyribosyl ribitol phosphate conjugated to tetanus protein; Hexavac; Aventis Pasteur MSD, Lyon, France) are compared with those of reference vaccines [diphtheria-tetanus-acellular pertussis-inactivated polio vaccine reconstituting lyophilized purified Haemophilus influenzae polysaccharide conjugated to tetanus protein vaccine (Pentavac; Aventis Pasteur MSD) and hepatitis B vaccine (H-B-Vax II; Aventis Pasteur MSD)] injected separately at the same visit in a prospective multicenter, comparative, open label trial. METHODS: Infants were randomized to receive Hexavac (n = 423) or Pentavac and H-B-Vax II (n = 425) as a primary immunization series at 2, 4 and 6 months of age. Seroprotection and seroconversion rates against all antigens at 1 month after the primary series were compared between the two vaccine groups with 95% confidence intervals (CI0.95) and were considered clinically equivalent (not inferior) when the upper limit of the 95% confidence interval on the difference (reference, hexavalent) was below predefined differences. RESULTS: Hexavac met and surpassed the pre-defined criteria for clinical equivalence to Pentavac and H-B-Vax II given concomitantly. It elicited similar seroprotection and seroconversion rates against all antigens. Seroprotection and seroconversion rates obtained 1 month after the third dose of Hexavac were >90% for all antigens. The postimmunization antibody geometric mean titers (GMT) for hepatitis B and purified Haemophilus influenzae polysaccharide were about 2-fold higher in infants who received the reference vaccines than in infants who had received Hexavac. GMTs for poliovirus antibodies tended to be enhanced in infants vaccinated with Hexavac. GMTs for all other antigens were very similar among both groups. Hexavac was generally well-tolerated. At least one local reaction was reported in 20.3% of Hexavac injections compared with 15.8% at the Pentavac injections site and 3.8% at the H-B-Vax II injections site. These reactions were generally mild and transient. At least one systemic adverse event was reported in 45.7% of Hexavac injections compared with 42.2% of Pentavac and H-B-Vax II injections (mild fever, irritability and drowsiness were most frequently reported). The frequency of adverse events was not significantly different between groups. No vaccine-related serious adverse event occurred during the study. CONCLUSION: This liquid hexavalent vaccine was generally well-tolerated and provided immune responses adequate to be protective against six infectious diseases with a single injection, given at 2, 4 and 6 months of age.

Antibodies, Bacterial↗
PubMed1999

New acellular pertussis-containing paediatric combined vaccines.

Combined pediatric vaccines have the advantages of conferring protection against multiple common infectious diseases with a reduced number of injections. Their use should lead to better compliance to recommended vaccination schedules. Diphtheria (D), tetanus (T) and whole-cell pertussis vaccine (P) have been successfully combined, with or without inactivated poliovirus vaccine (IPV) in the same syringe for many years. Recently developed acellular pertussis (aP) Haemophilus influenzae type B (Hib), inactivated poliomyelitis virus and hepatitis B vaccines are ideal candidates for inclusion in current combined vaccines. Nevertheless, the development of new combinations has to face preclinical and clinical issues: the appropriate formulation of the new antigen(s) and other vaccine components needs to be determined to ensure compatibility and guard against potential additive or unexpected adverse reactions; potential immunological interference between antigens and the negative impact of other vaccine components on immunogenicity may occur, and these have to be examined also. Whole-cell pertussis vaccines are highly protective against whooping cough, but the severe adverse reactions that these vaccines sometimes produce have led to hesitation over their use, including the decision of some countries to stop pertussis immunization. To increase the acceptability of pertussis vaccination, Pasteur Mérieux Connaught has developed a combined D, T and a two-component acellular pertussis vaccine (DTaP), composed of purified pertussis toxoid (PT) and filamentous haemagglutinin (FHA), which has been shown to be effective in an efficacy trial conducted in Senegal. Acellular DTaP vaccines are immunogenic and have a better safety profile than DTP vaccines, when given either for the primary series, for the booster vaccination or for both. In order to meet worldwide demands, the combined DTaP-IPV or DTP-IPV has been developed for countries where IPV is recommended. Following the encouragement of the WHO, an H. influenzae type B tetanus-conjugated (Act-HIB) vaccine, has been combined in a full liquid formulation with the whole-cell DTP. This vaccine showed a good safety and immunogenicity profile in infants and in toddlers. A combined DTaP-IPV-PRP-T vaccine (where the Act-HIB vaccine is reconstituted by the full-liquid DTaP-IPV) also has been successfully developed both for the primary series and for booster vaccination; although, a reduced immunogenicity against PRP observed after the primary series, this did not affect vaccine priming. Hepatitis B immunization campaigns targeting high-risk groups have failed to control the disease in areas of low endemicity. In 1992, the WHO recommended that hepatitis B vaccination should be integrated into the EPI in all countries by 1997-1999. For that purpose, hepatitis B vaccine is currently evaluated in pediatric combined vaccines. Developing new combination vaccines is a difficult but essential process for maintaining high immunization rates worldwide against infectious diseases, provided that the costs are acceptable. New combined vaccines including pneumococcal and meningococcal component are under wide-scale development.

Hepatitis B Vaccines↗
PubMed1999

Randomised study of the possible adjuvant effect of BCG vaccine on the immunogenicity of diphtheria-tetanus-acellular pertussis vaccine in Senegalese infants.

Following a study in Senegal (1990-1995) in which the relative efficacy of a diphtheria-tetanus-acellular pertussis vaccine (DTaP) was compared with that of a diphtheria-tetanus-whole-cell pertussis vaccine in children given a simultaneous injection of Bacille Calmette-Guérin (BCG) vaccine, this subsequent study was conducted to evaluate the possible adjuvant effect of the BCG vaccine on acellular pertussis vaccine components. A second objective was to compare the immunogenicity of these components when administered in accordance with a 2-4-6-month (spaced) schedule or an accelerated 2-3-4-month schedule. In all, 390 healthy Senegalese infants were randomly divided into three groups of 130 infants. Antibodies to acellular pertussis components were measured in serum samples obtained within 2 days of the first DTaP dose and 1 month after the third dose. BCG vaccine, given simultaneously with the DTaP vaccine, did not influence the immunogenicity of the acellular pertussis vaccine components when compared with separate administration of the two vaccines. Infants immunised according to a 2-4-6-month schedule had a significantly higher immune response than those immunised according to a 2-3-4-month schedule with respect to the response to pertussis toxoid assessed by seroneutralisation on Chinese hamster ovary cells (P<0.0001). These results suggest that BCG and DTaP vaccines can be given simultaneously without interference or enhancement and that more optimal immunogenicity is achieved with an extended than with an accelerated schedule.

Antibodies, Bacterial↗
PubMed1999

Reduction of retrosternal and pericardial adhesions with rapidly resorbable polymer films.

BACKGROUND: The formation of postoperative cardiac adhesions makes a repeat sternotomy time consuming and dangerous. Many attempts have been made to solve this problem by using either drugs to inhibit fibrinolytic activity or different types of pericardial substitutes. The results have not been satisfactory. METHODS: The efficacy of bioresorbable film prototypes made of polyethylene glycol (EO) and polylactic acid (LA) (EO/LA = 1.5, 2.5, and 3.0) in the prevention of adhesions after cardiac operations in canine models was tested. After desiccation and abrasion of the epicardium, a transparent bioresorbable film was placed over the heart. The pericardium was closed to allow intrapericardial adhesions (n = 32) or left open and attached to the chest wall to induce retrosternal adhesions (n = 17). Postoperative recovery was similar among the groups. Retrosternal and pericardial adhesions were evaluated at necropsy 3 weeks later by assessing area, tenacity, and density of the adhesions. RESULTS: In the control dogs, tenacious, dense adhesions were observed. In contrast, adhesion formation was reduced at all sites covered by the films. The bioresorbable films were efficacious in the reduction of adhesion formation between epicardium and pericardium or between epicardium and sternum after cardiac operation. The EO/LA 1.5 film most effectively prevented the early adhesions. CONCLUSIONS: The bioresorbable films (EO/LA = 1.5, 2.5, and 3.0) significantly reduced adhesion formation, with EO/LA = 1.5 (Repel CV) being optimal. As the barrier was rapidly resorbed, the capsule formation induced by permanent barriers was avoided.

Absorption↗
PubMed1998

Prevention of retrosternal adhesion formation in a rabbit model using bioresorbable films of polyethylene glycol and polylactic acid.

The purpose of this study was to test the efficacy of three bioresorbable films of polyethylene glycol (EO) and polylactic acid (LA) (EO/LA = 1.5, 2.5, and 3.0) in the prevention of adhesion formation between the epicardium and the sternum (retrosternal adhesions) in a rabbit model. Retrosternal adhesions were generated by sternotomy, pericardiotomy, and abrasion of the anterior epicardium. The adhesion barrier was placed between the epicardium and the sternum and sutured to the edge of the pericardium. Epicardial adhesions were evaluated 14-20 days later by assessing the area of the epicardium covered by adhesions. In the control rabbits, tenacious adhesions were observed between sternum and the central portion of epicardium (portion exposed through the pericardiotomy) which were difficult to dissect. When a bioresorbable film was placed over the pericardium, adhesion formation at the central strip of the epicardium (area between the sternum and the epicardium exposed through the pericardium) could be reduced or prevented. At this site, the areas of adhesion formation were 0% (EO/LA = 1.5), 8.4 +/- 2.8% (EO/LA = 2.5), and 5.6 +/- 4.7% (EO/LA = 3.0) of the central strip, significantly less than that observed in the control group, 78.0 +/- 5.8% (P < 0.01). At the anterior left and right and posterior apex of the heart (sites where the film was not placed), there were no differences between control and treatment groups. The films were completely resorbed at the time of necropsy in group EO/LA = 2.5 and 3.0. Small pieces of film were observed in group EO/LA = 1.5. In conclusion, the bioresorbable films [EO/LA = 1.5 (REPEL-CV), 2.5, or 3.0] were efficacious in the reduction of retrosternal adhesions to the epicardium.

Animals↗
PubMed1998

Nature of interaction between basic fibroblast growth factor and the antiangiogenic drug 7,7-(Carbonyl-bis[imino-N-methyl-4, 2-pyrrolecarbonylimino[N-methyl-4,2-pyrrole]-carbonylimino] )bis-(1, 3-naphthalene disulfonate).

PNU145156E (7,7-(carbonyl-bis[imino-N-methyl-4, 2-pyrrolecarbonylimino[N-methyl-4,2-pyrrole]-carbonylimino]) -bis-(1, 3-naphthalene disulfonate)) is a naphthalene sulfonic distamycin A derivative that interacts with heparin-binding growth factors. Because PNU145156E inhibits tumor angiogenesis, it was selected for clinical development. Picosecond time-resolved fluorescence emission and anisotropy were used to characterize the binding of PNU145156E to the basic fibroblast growth factor (a protein associated with tumor angiogenesis). A decrease in PNU145156E fluorescence lifetime was observed as a function of human basic fibroblast growth factor (bFGF) concentration. Nonlinear least-squares fitting of the binding isotherm yielded Kd = 145 nM for a single class of binding sites. Time-resolved anisotropy gave Kd = 174 nM. Kd = 150 nM was independently verified by quantitative high-performance affinity chromatography. The displaced volume of the complex, calculated from its rotational correlation time, fitted a sphere of 1:1 stoichiometry. These results account for the formation of a tight yet reversible PNU145156E:bFGF complex. An evaluation of PNU145156E fluorescence lifetimes in various solvents has highlighted the forces involved in stabilizing the complex. These are mostly electrostatic-hydrophobic in nature, with a relatively low contribution from hydrogen bonding. Both polar and nonpolar groups are involved on the protein-binding site within a largely hydrophobic cleft. A potential binding trajectory, based on a combination of these results with site-directed chemical modification and known bFGF x-ray structure, is suggested.

Binding Sites↗
PubMed1998

Evaluation of polyethylene glycol/polylactic acid films in the prevention of adhesions in the rabbit adhesion formation and reformation sidewall models.

OBJECTIVE: To assess the efficacy of bioresorbable films consisting of various polyethylene glycol 6000 and polylactic acid block copolymers on the formation and reformation of adhesions in rabbit models of adhesion development between the sidewall to the adjacent cecum and bowel. The composition of the different polymers was expressed by the number of monomeric units in the block, namely, ethylene oxide (EO) and lactic acid (LA), respectively. DESIGN: Studies of the efficacy of EO/LA films were conducted in rabbit sidewall adhesion formation studies in the presence and absence of blood and in rabbit adhesion reformation studies. REPEL (Life Medical Sciences, Edison, NJ), a film of EO/LA ratio 3.0 manufactured under commercial conditions, was also tested in these animal models. SETTING: University-based laboratory. ANIMALS: New Zealand white rabbits. INTERVENTION(S): Placement of films of various EO/LA ratios at the site of injury to the parietal peritoneum. MAIN OUTCOME MEASURE(S): Adhesion formation and reformation. RESULT(S): Films of various EO/LA ratios, Seprafilm (Genzyme, Cambridge, MA) and Interceed (Johnson and Johnson Medical, Arlington, TX) placed over an area of excised sidewall at the time of initial injury were highly efficacious in the prevention of adhesion formation. A film of EO/LA ratio 3.7, in contrast with Interceed, was also shown to maintain maximal efficacy in the reduction of adhesion formation in the presence of blood. Further, a film of EO/LA ratio 3.0 produced under commercial conditions, REPEL, was highly efficacious in reducing adhesion development in the rabbit models of adhesion and reformation. CONCLUSION(S): These studies suggest that bioresorbable EO/LA films reduced adhesion development in rabbit models of adhesion formation and reformation.

Abdomen↗
PubMed1998

Clinical acceptability and immunogenicity of a pentavalent parenteral combination vaccine containing diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis and Haemophilus influenzae type b conjugate antigens in two-, four- and six-month-old Chilean infants.

BACKGROUND: In recent years additional parenteral vaccines have been recommended for routine immunization of infants in the US and elsewhere. The ability to administer multiple vaccines as a single injection without unacceptably increasing reactogenicity or decreasing immunogenicity of any component would offer many practical advantages. METHODS: A randomized, open, controlled trial was conducted to assess the tolerance profile and immunogenicity, as well as to identify potential antigenic interferences, resulting from administration of a parenteral combination vaccine for infants. The vaccine contains diphtheria and tetanus toxoids, acellular pertussis antigens (DTaP), enhanced inactivated poliovirus (eIPV) and Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T). Infants (n=711) were randomly assigned to receive 1 of 5 regimens as the primary series at 2, 4 and 6 months of age, by group: (1) DTaP plus oral polio vaccine (OPV); (2) DTaP plus eIPV (separate injections); (3) DTaP-eIPV combined as a single injection; (4) DTaP-eIPV combined, plus a separate injection of PRP-T; or (5) DTaP-eIPV combined and reconstituting PRP-T, as a single injection. At 3, 5 and 7 months Groups 1, 2 and 3 received PRP-T. At 12 months all infants received a booster dose of DTaP reconstituting PRP-T as a single injection, plus a separate injection of measles, mumps and rubella vaccine. Groups 2, 3, 4 and 5 received OPV at 7 months, and all infants received OPV at 13 months. Serum immune responses were measured to the primary series at 2 and 7 months and to the booster dose at 12 and 13 months. RESULTS: Reaction rates were similar among groups. In the primary series combining eIPV with DTaP decreased geometric mean titers (GMTs) to diphtheria, tetanus and pertussis. In addition concomitant PRP-T (either simultaneous or combined) with DTaP-eIPV lowered anti-PRP and further decreased tetanus GMTs. Nonetheless in 100% of infants protective titers were achieved against diphtheria and tetanus (>0.01 IU/ml each) and against the poliovirus types 1, 2 and 3 after eIPV (Groups 2 to 5); 99% of infants (Groups 4 and 5) had protective titers against PRP (> or = 0.15 microg/ml). After boosting with DTaP/PRP-T decreased GMTs to diphtheria and PRP antigens were observed in the groups that received DTaP and eIPV combined. Nonetheless protective titers to diphtheria, tetanus and PRP occurred consistently. In contrast concomitant PRP-T with DTaP-eIPV enhanced the pertussis GMTs. CONCLUSIONS: We conclude that combined DTaP, eIPV and PRP-T in a single injection is well-tolerated and elicits an acceptable immune response to each component.

Adhesins, Bacterial↗
PubMed1997

Removal of dissolved O2 by a fluid membrane of Fomblin Y (perfluoro polyether): fluorescence of diphenylhexatriene in Fomblin Y.

O2 can be gently removed from solutions by contact with a "bulk fluid membrane" of the viscous and nearly inert perfluoro polyether Fomblin Y. A volume of Fomblin dissolves approximately 20 times more O2 than an equal volume of water. Hence, when a volume of aqueous solution which was in equilibrium with air is enclosed with an equal volume of Fomblin which had been flushed with argon, oxygen would diffuse into the Fomblin, leaving in the water only 5% of the oxygen that was there. When the Fomblin is stirred, diffusion is rather rapid. The residue can be removed either by placing an oxygen scavenger on the other side of the Fomblin or by flowing a trickle of deoxygenated Fomblin through the sample. Diphenylhexatriene, a fluorescent probe of cell membranes, can be dissolved in Fomblin Y and has a fluorescence lifetimes extending from 12 ns in O2 saturation to 30 ns (!) in the absence of oxygen. Stern-Volmer plots calibrated against a Clark electrode validate this system for oximetry. A general purpose anaerobic cuvette for fluorescence spectroscopy, containing the sample solution, a Fomblin compartment and the oxygen scavenger Na-dithionite is demonstrated.

Diphenylhexatriene↗
PubMed1995

[Mycobacterium kansasii infection in patients with human immunodeficiency virus infection].

We report a retrospective study of 12 caucasian men infected with HIV who had developed Mycobacterium kansasii infection (Mk). All patients had a low blood lymphocyte CD4 count (1-130, mean 15/mm3) and ten met the diagnostic criteria for AIDS. The 12 patients had pulmonary symptoms (dyspnea, cough) and fever. On chest X-ray, nodular, interstitial or diffuse parenchymal infiltrates, mediastinal and hilar adenopathies were observed. Two patients had pleural effusion, but none had cavitary lung disease. Mk was isolated by culture of sputum (n = 7), blood (n = 3), bronchial biopsy (n = 2) or bone marrow (n = 1). No patient had clinical extra-pulmonary disease. Survival after diagnosis was in average 7 months. Potential for therapeutic response is reviewed and documented.

AIDS-Related Opportunistic Infections↗
PubMed1991

Adhesion reformation: reduction by the use of Interceed (TC7) plus heparin.

Adhesions frequently develop after surgical procedures. Several groups have demonstrated that reduction of adhesion reformation is more difficult than reduction of adhesion formation. Previous studies have demonstrated the efficacy of Interceed (TC7) (oxidized regenerated cellulose) plus heparin in reducing adhesion formation. Adhesions were created using a previously standardized rabbit uterine horn model. After adhesiolysis, rabbits were assigned randomly to one of four groups: control, Interceed (TC7) alone, Interceed (TC7) plus 500 USP units heparin/horn, and Interceed (TC7) plus 1000 USP units heparin/horn. Adhesion reformation was evaluated 2 weeks later. Combination of the Interceed (TC7) barrier plus heparin resulted in a significant reduction of the adhesion reformation scores. It is concluded that Interceed (TC7) plus heparin is efficacious in reduction of both adhesion formation and adhesion reformation.

Animals↗
PubMed1991

Synergistic effects of INTERCEED(TC7) and heparin in reducing adhesion formation in the rabbit uterine horn model.

Surgical adjuvants are commonly employed to reduce the frequency of postoperative adhesion development after reproductive pelvic surgery. The ability of indomethacin, promethazine dexamethasone, Intralipid, progesterone, and heparin to reduce adhesion formation in combination with INTERCEED(TC7) (Johnson and Johnson Medical, Inc., New Brunswick, NJ), an absorbable barrier that alone reduces adhesion formation, was examined in a rabbit uterine horn model. A significant reduction in adhesion formation was only observed with the combination of INTERCEED(TC7) plus heparin. In addition studies, heparin delivery by intraperitoneal (IP) lavage, intravenous injection, or intra-abdominal instillation failed to demonstrate efficacy. Similarly, heparin delivery with other barriers or IP instillates (carboxymethylcellulose or 32% Dextran 70) failed to reduce adhesion formation. We conclude that INTERCEED(TC7) can be efficaciously utilized as a carrier to deliver heparin to traumatized surfaces, thereby reducing adhesion formation.

Animals↗
PubMed1981

Probing the micelle/water interface by a rapid laser-induced proton pulse.

The laser-induced pH jump (Gutman, M. and Huppert, D.J. (1979) Biochem. Biophys. Methods 1, 9-19) has a time resolution capable of measuring the diffusion-controlled rate constant of proton binding. In the present study we employed this technique for measuring the kinetics of protonation-deprotonation of surface groups of macromolecules. The heterogeneous surface of proteins excludes them from serving as a simple model, therefore we used micelles of a neutral detergent (Brij 58) as a high molecular weight structure. The charge was varied by the addition of a low concentration of sodium dodecyl sulfate and the surface group with which the protons react was an adsorbed pH indicator (bromocresol green or neutral red). The dissociation of a proton from adsorbed bromocresol green is slower than that from free indicator. This effect is attributed to the enhanced stabilization of the acid form of the indicator in the pallisade region of the micelle. The pK shift of bromocresol green adsorbed on neutral micelles is thus quantitatively accounted for by the decreased rate of proton dissociation. Indicators such as neutral red, which are more lipid soluble in their alkaline form, do not exhibit such decelerated proton dissociation in their adsorbed state nor a pK shift on adsorption to neutral micelles. The protonation of an indicator is a diffusion-controlled reaction, whether it is free in solution or adsorbed on micelles. By varying the electric charge of the micelle this rate can be accelerated or decelerated depending on the total charge of the micelle. The micellar charge calculated from this method was corroborated by other measurements which rely only on equilibrium parameters. The high time resolution of the pH jump is exemplified by the ability to estimate the diffusion coefficient of protons through the hydrated shell of the micelle.

Colloids↗