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Biomedical subjects

H F Guiot

Publications and source records attributed to H F Guiot.

At least 37 records · Page 2Linked to original sources

Decontaminating efficacy of ciprofloxacin in an animal model.

A study was performed to assess the suppressive effect of ciprofloxacin on the aerobic gram-negative flora of the gastrointestinal tract in mice in relation to its effect on colonization resistance. Ciprofloxacin exhibited a potent decontaminating effect, with the maximum effect being reached at a dose of 8 mg/kg/day. At this dose aerobic gram-negative rods were eliminated from the gastrointestinal tract within 24h without any adverse influence on the parameters of colonization resistance measured.

Animals↗

Modulation of the host flora.

Modulation of the bacterial flora of patients with a high risk of acquiring an infection can be achieved in several ways. The approach used in the Leiden University Hospital is based on selective elimination of the aerobic bacteria in the oropharyngeal cavity and intestinal tract, leaving the anaerobic flora intact. This kind of selective modulation of the host flora has an advantage in that it does not affect the colonization resistance provided by bacterial antagonism, which prevents colonization by resistant but potentially pathogenic bacteria or fungi. The elimination of aerobic bacteria combined with nursing in protective isolation and consumption of food with few bacteria has led to a significant reduction of the incidence of major and fatal infections in patients during episodes of severe granulocytopenia. From these results it may be concluded that the objective of selective antibiotic modulation, namely, the prevention of infections, can be achieved with this approach.

Animals↗

Protein loss during acute graft-versus-host disease: diagnostic and clinical significance.

In 31 consecutive patients who received an allogeneic bone marrow transplantation the loss of proteins during the period at risk for acute graft-versus-host disease (aGVHD) was studied in order to determine whether the quantity of protein loss could be used for grading the severity of aGVHD. It was shown that the grade classified on the basis of the severity of skin rash, the quantity of diarrhea and the seriousness of cholestasis, correlated with serum albumin loss, intestinal plasma loss (expressed by the intestinal alpha 1-antitrypsin clearance) and the occurrence of inflammatory cells (leukocytes) in feces. The quantity of albumin lost by intestinal route accounted for only one third of the total albumin loss. To investigate whether the remaining part of it could be explained by capillary leakage elsewhere in the body, leakage of antileukoprotease from the tissue of the respiratory tract into the blood was measured. It was shown that the serum concentration of this proteinase inhibitor correlated with albumin loss. This means that capillary leakage also occurs in the lung during aGVHD. In conclusion, the loss of proteins can be used as a parameter of the severity of aGVHD once the proper diagnosis has been established. It appears that a combination of the current 'familiar' grading system and SAL yields a more objective classification system with a greater prognostic value.

Acute Disease↗

Selective antimicrobial modulation of the intestinal microbial flora for infection prevention in patients with hematologic malignancies. Evaluation of clinical efficacy and the value of surveillance cultures.

To confirm the results obtained in an earlier study, the incidence of infection was evaluated in 54 patients (62 periods of admission), nursed in conventional rooms and given a regimen of antimicrobial agents intended to modulate the intestinal flora selectively as a method to prevent infection during severe granulocytopenia. In 62 patients receiving selective antimicrobial modulation (SAM), 18% acquired major infections which was similar to 19% in patients on SAM in an earlier double-blind placebo controlled study and lower than 47% in the controls. Evaluation of a large number of surveillance cultures showed that the presence of specific potentially pathogenic aerobic bacteria was associated with the occurrence of major infection. If the bacterial species in question were not found in the cultures the chance of becoming infected was less than 5%, whereas the chance ranged between 42 and 62% depending on the species involved when these microorganisms were isolated.

Acute Disease↗

Selective antimicrobial modulation of the intestinal flora of patients with acute nonlymphocytic leukemia: a double-blind, placebo-controlled study.

Thirty-three patients with acute nonlymphocytic leukemia were studied during remission-induction treatment in a double-blind, placebo-controlled, randomized study to ascertain the effect on the incidence of infection of an oral regimen of selective antimicrobial modulation (SAM). A decrease in the number of major acquired infections was observed: three infections occurred in 16 patients receiving the SAM regimen compared with eight infections in 17 patients given the placebo. The reduction of infection was correlated with a reduction of fever, with a reduction of the frequency of administration of antimicrobial agents for the treatment of infection, and with the selective elimination of aerobic and facultative anaerobic gram-negative rods from the digestive tract. Substantial unfavorable side effects were not observed.

Adolescent↗

Anti-thymocyte globulin treatment for aplastic anemia.

20 patients with severe aplastic anemia were treated with anti-thymocyte globulin (ATG), 6 of them in combination with haplo-identical bone marrow. 7 patients (35%) showed a good clinical response within 6 months; they were off transfusions and had greater than or equal to 0.8 x 10(9)/l neutrophils. ATG had the greatest effect on red-cell production and the least on platelet production. The hematological recovery with ATG could not be predicted from the bone-marrow histology, CFU-c growth, or clinical data. However, patients with strong HLA antibodies seemed to respond more often. The actuarial survival was 55% at 5 years. Under intensive supportive care, even 7 out of 12 non-responders were alive after 1 year. ATG appears to be a useful form of therapy for patients with severe aplastic anemia who are not candidates for bone-marrow transplantation.

Adolescent↗

Role of competition for substrate in bacterial antagonism in the gut.

Small slices of agar, each containing about 10(5.5) Escherichia coli organisms, were preincubated either in the contents of rat cecum or in brain heart infusion broth for 2 h and then were transferred to a small sample of saline. The purpose of these experiments was to examine the ability of E. coli to grow on the substrate that penetrated from the contents of rat cecum into the agar slices. It appeared that preincubation in brain heart infusion broth gave rise to abundant growth, whereas only poor growth occurred after preincubation in the contents of rat cecum. This poor growth was completely reversed by adding brain heart infusion. The same experiments were repeated under anaerobic conditions, in which growth on substrate that penetrated from the contents of rat cecum into the agar slices was extremely poor. This extremely poor growth under anaerobic conditions was reversed to abundant growth by adding brain heart infusion broth. The addition of nitrate as an electron acceptor also stimulated growth of E. coli. Similar results were obtained with other bacteria and with human feces. The results can be interpreted as a demonstration that under anaerobic conditions such as occur in large intestines, bacterial antagonism is caused in a high degree by competition for substrate.

Anaerobiosis↗

Selective antimicrobial modulation of human microbial flora: infection prevention in patients with decreased host defense mechanisms by selective elimination of potentially pathogenic bacteria.

To reduce the frequency and severity of bacterial infection, selective antimicrobial modulation (SAM) was applied in 39 patients with severely decreased host defense mechanisms. The objective was to eliminate potentially pathogenic aerobic microorganisms with minimal disturbance of the normal anaerobic bacterial flora. Elimination of potentially pathogenic aerobic microorganisms was easily accomplished in patients not infected at hospitalization. The anaerobic flora seemed to be undisturbed, and selection of or overgrowth with resistant microorganisms did not occur. The microbiologic results of the SAM regimen correlated with the incidence of infection. Only three major infections occurred in 23 patients who were free of potentially pathogenic microorganisms; 10 major infections occurred in 16 patients who were not free of potential pathogens. Seven of these 10 infections were present at hospitalization. The incidence of major infections was 47% in the patients on the SAM regimen and 82% in a group of control patients with a similar risk of infection.

Adolescent↗