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Biomedical subjects

S Bernard

Publications and source records attributed to S Bernard.

At least 109 records · Page 6Linked to original sources

Warm versus cold blood cardioplegia--is there a difference?

This experimental study sought to compare the effectiveness of warm blood cardioplegia versus cold blood cardioplegia in protecting areas of ischemic myocardium during urgent coronary revascularization. In 40 adult pigs, the second and third diagonal vessels were occluded with snares for 90 minutes. All animals were then placed on cardiopulmonary bypass and underwent 45 minutes of cardioplegic arrest followed by 3 hours of reperfusion during which time the coronary snares were released. During the period of cardioplegic arrest, 10 pigs received antegrade continuous warm blood cardioplegic solution (37 degrees C) at 100 ml/min; 10 animals received retrograde warm blood cardioplegic solution at 100 ml/min; 10 received intermittent, antegrade cold blood cardioplegic solution (4 degrees C), and 10 animals received intermittent, antegrade/retrograde cold blood cardioplegic solution. Hearts protected with antegrade warm blood cardioplegic solution had the lowest pH values in the area at risk (6.59 +/- 0.10 antegrade warm blood cardioplegia versus 6.80 +/- 0.10 retrograde warm blood cardioplegia versus 6.72 +/- 0.18 antegrade cold blood cardioplegia versus 6.85 +/- 0.15 antegrade/retrograde cold blood cardioplegia and the highest area of necrosis (42% +/- 3% antegrade warm blood cardioplegia versus 26% +/- 2% [p < 0.05 from antegrade warm blood cardioplegia] retrograde warm blood cardioplegia versus 31% +/- 2% [p < 0.05 from antegrade warm blood cardioplegia] antegrade cold blood cardioplegia versus 21% +/- 2% [p < 0.05 from antegrade warm blood cardioplegia] antegrade/retrograde cold blood cardioplegia). We conclude that in the presence of an acute coronary occlusion with ischemic myocardium, warm blood cardioplegic solution should be given in a continuous retrograde fashion and does not result in myocardial protection superior to the protection that can be achieved with antegrade/retrograde cold blood cardioplegic solution.

Animals↗

Effect of fixation on the detection of transmissible gastroenteritis coronavirus antigens by the fixed-cell immunoperoxidase technique.

The effect of various fixatives and detergents on the in vitro detection of the viral determinants which are expressed in swine testis cells infected with the transmissible gastroenteritis coronavirus (TGEV) was studied using a microwell immunoperoxidase technique. When compared with glutaraldehyde and formaldehyde, 0.1% paraformaldehyde was found to be the fixative of choice for the detection of these determinants on the membranes of infected cells. Among dehydrating fixatives, 80% acetone or a mixture of acetone and ethanol or of acetone, methanol and ethanol were found to be the best fixatives for the detection of these viral determinants which are expressed in infected cells. In the case of acetone, the temperature of fixation and its concentration in the fixative preparation were found to be important. The treatment of 0.05% glutaraldehyde-fixed, infected cells with 0.1% saponin or 0.1% paraformaldehyde-fixed, infected cells with 1%NP-40 led to satisfactory detection of viral determinants. Using Triton X-100 to render cells permeable, the quantities of N and M antigen detected in TGEV-infected cells prefixed with either 0.05% glutaraldehyde or 0.1% paraformaldehyde were equal to those of 80% acetone-fixed, TGEV-infected cells while the quantity of S antigen detected was diminished. The effect of other detergents such as zwittergent, empigen BB, Chaps and N-lauroylsarcosine on the detection of viral determinants was also studied.

Acetone↗

Pathogenicity and antigen detection of the Nouzilly strain of transmissible gastroenteritis coronavirus, in 1-week-old piglets.

We compared the pathogenicity and the sites of multiplication of the attenuated Nouzilly strain, with the highly passaged Purdue-115 and the virulent Gep II strains of transmissible gastroenteritis (TGE) coronavirus, in 1-week-old weaned piglets. The immunohistochemical peroxidase technique, with an antiviral nucleoprotein monoclonal antibody, was used for the localization of the multiplication sites, in the intestine and other organs. The Gep II and the Purdue-115 strains, administered orally to piglets, caused clinical signs and lesions of TGE. These strains multiplied within the intestinal tract in the enterocytes of the jejunum and ileum, Peyer's patches and mesenteric lymph nodes. In view of the small numbers of infected cells in the tonsils, spleen, kidney, liver and lung, these tissues are not considered to be preferential multiplication sites. The attenuated Nouzilly strain multiplies only in the ileum and the mesenteric lymph nodes. The variation in the tropism for particular parts of the intestine (with the preferential localization of the virus in the ileum rather than the jejunum), could be related to the high degree of attenuation of the Nouzilly strain.

Animals↗

Bacillus cereus endocarditis: report of a case and review.

Bacillus cereus is a ubiquitous organism that infrequently causes serious infections. We report a patient with B. cereus endocarditis involving a mechanical aortic valve. Data for 10 cases of B. cereus endocarditis reported in the literature are summarized. B. cereus is resistant to many commonly used antibiotics, a finding that has clinical significance for empirical antibiotic selection in patients with suspected endocarditis. Infection in patients with valvular heart disease in the few cases reported is associated with significant mortality and morbidity.

Adult↗

Reduction of infarct size with coronary venous retroperfusion.

BACKGROUND: The purpose of this study was to determine whether coronary venous retroperfusion with pressure-controlled intermittent coronary sinus occlusion (PICSO) alone and in combination with coronary venous substrate enhancement using L-glutamate would decrease ischemic damage after surgical revascularization for an acute coronary occlusion. METHODS AND RESULTS: In 40 pigs, the second and third diagonal vessels were occluded with snares for 90 minutes followed by 30 minutes of cardioplegic arrest and 180 minutes of reperfusion with the coronary snares released. During the period of coronary occlusion, 10 pigs received PICSO using a balloon-tipped triple-lumen catheter in the coronary sinus; 10 pigs received PICSO plus oxygenated blood transfused retrograde via the PICSO catheter (7 ml/min), 10 pigs received PICSO plus an oxygenated blood L-glutamate (13 mM) solution, and 10 pigs received neither PICSO, blood, nor L-glutamate through the coronary sinus (unmodified). Hearts treated with PICSO had higher wall motion scores (1.27 +/- 0.33 for unmodified, 2.40 +/- 0.40* for PICSO, 2.45 +/- 0.20* for PICSO plus blood, 2.85 +/- 0.30* for PICSO plus L-glutamate; *p < 0.05 from unmodified where 4 is normal to -1 is dyskinesia), lower area of necrosis-to-area of risk ratio using histochemical staining techniques (73 +/- 4% for unmodified, 27 +/- 4 for PICSO; 18 +/- 2* for PICSO plus blood, 12 +/- 1* PICSO plus L-glutamate; *p < 0.05 from unmodified), significantly less tissue acidosis (pH) compared with the unmodified group (pH, -0.41 +/- 0.13 for unmodified, -0.16 +/- 0.03* for PICSO, -0.19 +/- 0.02* for PICSO plus blood, -0.20 +/- 0.08* for PICSO plus L-glutamate; *p < 0.05 from unmodified). CONCLUSIONS: Coronary venous retroperfusion with PICSO alone and in combination with coronary venous substrate enhancement using L-glutamate significantly decreases ischemic damage during urgent surgical revascularization.

Angioplasty, Balloon, Coronary↗

Protection against Chlamydia psittaci in mice conferred by Lyt-2+ T cells.

A murine model was used to study the respective roles of L3T4+ and Lyt-2+ T cells in protection against Chlamydia psittaci. Donor mice were intravenously (i.v.) infected with 1 x 10(5) plaque-forming units (PFU) per mice of live C. psittaci. One month after inoculation, splenic cells from donors were transferred into syngenic recipients (5 x 10(7) cells/mouse). As measured by splenic colonization on Day 6 after i.v. challenge (1 x 10(5) PFU/mouse), transfer with primed (untreated) cells conferred a 3 log protection in this model. In vitro treatment, before transfer, of splenic cells with anti-Lyt-2 monoclonal antibody (mAb) and complement, markedly impaired the protection in comparison with control mice transferred with primed untreated cells, whereas treatment with anti-L3T4 mAb did not reduce the transferred protection. Resistance to a reinfection with C. psittaci was also studied after selective in vivo depletion of L3T4+ and Lyt-2+ T cells. One month after primary infection, mice were treated with anti-L3T4 or anti-Lyt-2 mAb and challenged thereafter (i.v., 1 x 10(5) PFU). The splenic colonization on Day 6 after challenge demonstrated that treatment with anti-Lyt-2 mAb impaired resistance against a subsequent infection with C. psittaci. Treatment with anti-L3T4 mAb in vivo had no effect on protection, as previously described in vitro. The mechanisms by which Lyt-2+ T cells could participate in the elimination of bacteria were discussed.

Animals↗

Isolation of Bacillus sphaericus biotin synthesis control mutants: evidence for transcriptional regulation of bio genes.

The genes involved in biotin synthesis have recently been isolated from Bacillus sphaericus [Gloeckler et al., Gene 87 (1990) 63-70]. Sequence analysis revealed that they are organized into two gene clusters, designated bioXWF and bioDAYB. The 5'-noncoding region of the bioD locus fused to the xylE reporter gene was inserted into the Gram-positive pUB110 replicon and the resulting plasmid was introduced into B. sphaericus IFO3525. Transformants expressed the xylE gene only if the biotin concentration in the growth medium remained below 50 ng/ml. After mutagenesis, colonies were screened for their ability to express the chromogenic marker in the presence of an excess of biotin. Most of these mutants escaped biotin repression of xylE gene expression. Classical genetic analysis showed they formed two main categories: chromosomal mutations, pleiotropically acting in trans on both bioXWF and bioDAYB 5'-noncoding regions, in which a 15-bp region common to both promoters represented a hot-spot for the second class of plasmid-associated mutations. These results, completed by the identification of transcription start points for the bioD and bioX genes, strongly suggest that this 15-bp sequence overlaps the site of a biotin-mediated negative regulation circuit controlling the transcription of the bio genes.

Amino Acid Sequence↗

Induction of lactogenic immunity to transmissible gastroenteritis virus of swine using an attenuated coronavirus mutant able to survive in the physicochemical environment of the digestive tract.

A transmissible gastroenteritis (TGE) coronavirus mutant (188-SG), selected as attenuated and resistant to acidity and proteases of the digestive tract of adult pigs, was used as vaccine ("Nouzilly strain") in sows to protect suckling piglets against a challenge exposure carried out with a highly virulent TGEV strain. The pregnant sows were immunized once (42-49 days before farrowing) or twice (42-49 and 7-15 days before farrowing) by the oral, intramuscular or conjunctival route with the 188-SG strain. Sows exposed to virulent TGEV in the field and experimentally infected sows (two oral inoculations during pregnancy) were used as positive controls leading to high protection. The neutralizing antibody response to vaccination and/or infection was studied in serum and milk. No protection against mortality was observed in the litters of (1) the nine seronegative, susceptible sows, with piglet mortality of 65/70, (2) the seven once orally vaccinated sows, with mortality of 44/54, (3) the seven sows vaccinated twice by the conjunctival route, with mortality of 55/76. Moderate protection was observed in (1) the eight sows vaccinated intramuscularly twice with piglet mortality of 36/90, (2) the seven orally and intramuscularly vaccinated sows with piglet mortality of 31/51. In of 3 contrast, improved protection was observed in (1) the 10 sows vaccinated twice orally, with piglet mortality of 23/95, (2) the four naturally infected sows with piglet mortality of 6/41, (3) the six sows experimentally infected with virulent TGEV with piglet mortality of 1/59. No correlation was found between neutralizing antibodies titers in serum and milk and protection rate of the piglets. The results indicate that relative protective lactogenic immunity against TGEV is induced only by repeated ingestion of the attenuated 188-SG strain of TGEV.

Administration, Oral↗

A phase I trial of alpha-interferon in combination with pentostatin in hematologic malignancies.

Pentostatin, a novel inhibitor of adenosine deaminase, has shown activity in various lymphoid malignancies of both the T and B cell lineage. This agent has unique side effects and in general myelosuppression has been mild. Interferon has both antiviral and antineoplastic properties. This agent has shown activity in hairy cell leukemia, chronic granulocytic leukemia, low grade lymphoma, and myeloma. Side effects from interferon are in general dissimilar to those that have been seen with pentostatin and in particular myelosuppression has not been a major toxicity with low doses of interferon. This current trial explored the combination of pentostatin and interferon in hematologic malignancies. Fifteen patients were enrolled in this phase I trial at a fixed dose of pentostatin of 4 mg/m2 biweekly and interferon at doses of 0.5, 1, 2, or 4 million units/m2 of interferon. At the first three dose levels of interferon nausea and vomiting were the predominant toxicity and appeared to worsen with time on study. Fatigue also was seen at the lowest level of interferon and was severe enough to cause two individuals to discontinue the study medications. At higher dose levels of interferon, myelosuppression, nausea and vomiting, and fatigue were the predominant toxicities. One patient with hairy cell leukemia had a complete response and a second patient with T cell cutaneous lymphoma had a partial response which lasted for 6 to 7 weeks. The maximum tolerated dose of interferon with pentostatin in this patient population was four million units/m2.

Adult↗

Superiority of retrograde cardioplegia after acute coronary occlusion.

Because antegrade cardioplegia may limit the distribution of cardioplegia beyond a coronary occlusion, this study was undertaken to determine whether retrograde coronary sinus cardioplegia provides superior myocardial protection during revascularization of an acute coronary occlusion. In 20 adult pigs, the second and third diagonal branches were occluded with a snare for 1 1/2 hours. Animals were then placed on cardiopulmonary bypass and underwent 30 minutes of ischemic arrest with multidose, potassium, crystalloid cardioplegia. In 10 animals, the cardioplegia was given antegrade through the aortic root, whereas in 10 others, it was given retrograde through the coronary sinus. After the arrest period, the coronary snares were released and all hearts were reperfused for 3 hours. Postischemic damage in the myocardium beyond the occlusions was assessed by wall motion scores using two-dimensional echocardiography (4 = normal to -1 = dyskinesia), the change in myocardial pH from preischemia, and the area of necrosis/area of risk (histochemical staining). Hearts protected with retrograde coronary sinus cardioplegia had less tissue acidosis (change in pH = 0.08 +/- 0.03 versus 0.41 +/- 0.13; p less than 0.05), higher wall motion scores (2.0 +/- 0.6 versus 1.3 +/- 0.3; not significant), and less myocardial necrosis (43.4% +/- 3.6% versus 73.3% +/- 3.5%; p less than 0.0001). We conclude that retrograde coronary sinus cardioplegia provides more optimal myocardial protection than is possible with antegrade cardioplegia after revascularization of an acute coronary occlusion.

Acid-Base Equilibrium↗

Continuous versus intermittent cardioplegia in the presence of a coronary occlusion.

Coronary artery occlusions can alter the distribution of cardioplegia and result in ischemic damage. This study was undertaken to determine whether continuous antegrade cardioplegia delivery would result in colder temperatures and provide better washout of acid metabolites than is possible with intermittent antegrade cardioplegia when coronary occlusions are present. Twenty pigs were placed on cardiopulmonary bypass and underwent 2 hours of ischemic arrest with occlusion of the middle left anterior descending coronary artery followed by 1 hour of reperfusion without occlusion of that artery. Ten pigs received intermittent (every 20 minutes) antegrade potassium crystalloid cardioplegia (4 degrees C), and 10 others had the same solution given continuously (30 mL/min). Cardioplegia distribution was assessed by continuous monitoring of myocardial pH (Khuri pH probe) and temperature in the region beyond the occlusion of the left anterior descending coronary artery. Both cardioplegic techniques resulted in tissue acidosis (continuous group, 6.69 +/- 0.08, versus intermittent group, 6.73 +/- 0.07; not significant). Average temperature in the left anterior descending coronary artery during arrest was also similar in both groups (continuous group, 18.3 degrees +/- 0.5 degrees C, versus intermittent group, 18.2 degrees +/- 0.5 degrees C). Because of these metabolic changes, both cardioplegic techniques resulted in abnormal wall motion in the anteroseptal region using two-dimensional echocardiography, but the scores were not significantly different (continuous group, 1.5 +/- 0.3, versus intermittent group, 1.6 +/- 0.4; 4 = normal to 0 = dyskinesia).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biotin formation by recombinant strains of Escherichia coli: influence of the host physiology.

Strains of Escherichia coli were transformed with different plasmids bearing the gene clusters bioXWF and bioDAYB isolated from the Gram positive bacterium Bacillus sphaericus. These genes encode for the enzymes involved in the metabolic pathway which synthesizes biotin from the precursor pimelic acid. Transformed E. coli strains were grown in bioreactors to reach a biomass of 18 g l-1 cell dry weight in 1 litre batch culture with substrate feeding and approximately 50 g l-1 in 10 l fed batch culture. Improved yields of total vitamers and biotin formed in these processes were achieved after a comparative analysis of different culture conditions, medium compositions, host strains and expression systems. Production of 27 mg l-1 of biotin and 200 mg l-1 of vitamers was achieved in 1 litre batch culture. Using a 10-1 fed batch process, biotin and vitamer concentrations reached maximum values of 45 mg l-1 and 350 mg l-1, respectively.

Bacillus↗

Fixed-cell immunoperoxidase technique for the study of surface antigens induced by the coronavirus of transmissible gastroenteritis (TGEV).

An immunoperoxidase technique performed on the TGEV-infected cells was developed for detection of virus-induced antigens. The presence of M antigen of TGEV on the surface of infected cells was demonstrated by this technique. This finding is in contrast to the M protein of murine hepatitis coronavirus which migrates to the Golgi apparatus but is not transported to the plasma membrane. The time course of appearance M and S antigens on the surface of TGEV-infected cell can be studied by this technique.

Animals↗

Severe lactic acidosis following theophylline overdose.

The patient with theophylline overdose commonly presents with gastrointestinal, cardiovascular, neurologic, and electrolyte abnormalities. Respiratory alkalosis is the most common acid-base alteration, but mild metabolic acidosis has been reported. Two cases of severe lactic acidosis (pH 6.67 and 6.63) in patients without hypoxemia, shock, or prolonged seizure activity are reported. Possible causative mechanisms and aspects of therapy are discussed. Theophylline toxicity should be considered when an unconscious patient with concurrent severe metabolic acidosis presents to the emergency department.

Acidosis, Lactic↗

Critical factors for the reversal of methotrexate cytotoxicity by folinic acid.

The cytotoxicity of methotrexate (MTX) on representative human tumour cell lines (two cell lines from head and neck carcinomas, two from breast carcinomas, two from osteosarcomas and one lymphoblastoid cell line) was evaluated to: (1) examine the optimal time interval between MTX and folinic acid (FA) administration; (2) determine the critical FA/MTX concentration ratios; and (3) compare the relative effects of the equimolar mixture d,I-FA and I-FA. The cytotoxic effects of MTX were assessed by the MTT semi-automated test. For all of the cell lines tested, a significant inverse relationship was noted between the degree of MTX cytotoxicity reversal and the duration of the time interval between MTX and FA administration. Overall an 18-24 h interval between MTX and FA represented a time-threshold after which MTX effects could not efficiently be reversed by FA in most cell lines. With shorter time intervals between MTX and FA, MTX cytotoxicity could be partially on even totally reversed by FA; the intensity of reversal varied among the cell lines tested, and depended on the FA/MTX ratio. Regardless of the interval between MTX and FA, analysis of the various FA/MTX ratios revealed a significant direct relationship between this ratio and the percentage of recovery. Presence of the d-form had no influence on the MTX rescue capacity of the I-form; this suggests that the presence of the d-FA is unlikely to have any significant clinical consequences.

Antineoplastic Combined Chemotherapy Protocols↗

Dose reduction without loss of efficacy for 5-fluorouracil and cisplatin combined with folinic acid. In vitro study on human head and neck carcinoma cell lines.

Folinic acid (FA) and cisplatin (CDDP) both potentiate the cytotoxicity of 5-fluorouracil (5-FU). The activity of various drug combinations including 5-FU, CDDP and FA was tested on two human cell lines derived from squamous cell carcinomas of the head and neck. Cytotoxicity was assessed by the semi-automated colorimetric MTT test. The drugs were tested in clinically achievable conditions (concentrations and duration of exposure). The dose response curves for 5-FU (0-100 ng ml-1) associated with FA (10(-7)-10(-5) M) reflected a progressive increase in 5-FU cytotoxicity with increasing FA concentrations. When CDDP (0-5 micrograms ml-1) was associated with 5-FU, CDDP-mediated enhancement of 5-FU cytotoxicity was apparent only when CDDP was given before 5-FU. The triple association CDDP, 5-FU and FA was also tested. In this case, for an identical final cytotoxicity, the presence of FA (10(-6) M) permitted reduction of the 5-FU concentration between 24.2 and 42% and reduction of the CDDP concentration between 13.8 and 72.7%. These observations may be beneficial for the design of more rational therapeutic trials associating CDDP, 5-FU and FA.

Antineoplastic Combined Chemotherapy Protocols↗

Composition of uterine flushings from Large White and prolific Chinese Meishan gilts.

This study examined differences in selected components of uterine secretions from Large White and prolific Chinese Meishan gilts during the oestrous cycle or early pregnancy. Total recoverable protein, uteroferrin (measured as acid phosphatase activity), acyl aminopeptidase, calcium, sodium, potassium, immunoglobulins A and G, glucose, fructose, oestradiol-17 beta, and prostaglandins F2 alpha (PGF2 alpha) and E2 (PGE2) in uterine flushings were measured. During the oestrous cycle, breed effects were detected only for total protein (P = 0.07), which tended to be higher for Large White gilts. However, for pregnant gilts, total recoverable glucose (P less than 0.05), fructose (P less than 0.05) sodium (P less than 0.05), immunoglobulin A (P less than 0.01), PGF (P less than 0.01), PGE (P less than 0.01), and acyl aminopeptidase (P less than 0.05) were greater in uterine flushings from Meishan gilts. Only uteroferrin was higher (P = 0.06) in uterine flushings from Large White gilts. Concentrations of prolactin were higher (P less than 0.05) in plasma from cyclic or pregnant Meishan gilts, but concentrations of total oestrogens and progesterone were not affected by pregnancy status or breed. These results suggest that Meishan conceptuses, individually or collectively, are more stimulatory to endometrial secretion and/or transport of the components of histotroph into the uterine lumen, or that the endometrium of Meishan gilts is more sensitive to conceptus signals responsible for the accumulation of histotroph in the uterine lumen.

Acid Phosphatase↗

Ondansetron for the prevention of emesis induced by high-dose cisplatin. A multi-center dose-response study.

To determine a dose-response relationship of ondansetron for the prevention of emesis induced by high-dose cisplatin and to study the efficacy of the extended dosing schedule of ondansetron during 20 hours after cisplatin administration, 36 patients with malignant neoplasms who had not previously received chemotherapy but who were currently receiving cisplatin were treated. These patients received a six-dose regimen of 0.01 mg/kg (low dose) or 0.18 mg/kg (high dose) of ondansetron. Seven (41%) patients in the high-dose group had no emesis and four (24%) patients had one or two episodes. One (5%) patient in the low-dose group had no emesis and four (21%) patients had one or two episodes. The difference in the number of emetic episodes was significant (P less than 0.02). Fifty percent of the high-dose patients reported no nausea or mild nausea, compared with 11% of the low-dose patients. Clinical adverse events included mild, transient headache and dizziness in the high-dose group and headache and diarrhea in the low-dose group, with no significant laboratory abnormalities. There is a parallel relationship between the ondansetron doses and the antiemetic efficacy. The response rate for the six-dose regimen of 0.18 mg/kg was not superior to that for the previously reported 0.18 mg/kg regimen given in a three-dose schedule in a similar clinical setting.

Adult↗