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Biomedical subjects

L Verbist

Publications and source records attributed to L Verbist.

At least 55 records · Page 3Linked to original sources

Orthodeoxia and platypnea in liver cirrhosis: effects of propranolol.

Chronic liver disease is well known to be associated with pulmonary abnormalities. Hypoxemia, clubbing, cyanosis and hyperventilation are common. The hypoxemia in cirrhotic patients has several causes: diffuse shunts due to intrapulmonary arteriolar vasodilatation, impaired hypoxic vasoconstriction, impaired matching of ventilation to perfusion, pleural effusions and diaphragmatic dysfunction. Because of gravity, shifting of blood to the dilated precapillary beds of the lung bases results in an increased hypoxemic dyspnea when the patient is in the upright position, also known as orthodeoxia and platypnea. It has only been described in 5% of the cirrhotic patients and has not been described in a Belgian refereed journal (Medline literature search 1983-Aug 1993). It should be considered in the initial differential diagnosis of hypoxemia in patients with liver cirrhosis and dyspnea. Measuring arterial blood gases in the lying and upright position can prevent further invasive investigations, and whole body nuclide scan with technetium-99m macroaggregated albumin can confirm the diagnosis. Standard therapy with spironolactone (Aldactone) can worsen the condition and we found no additional benefit of beta-antagonists (propranolol/Inderal) in the reduction of the shunt fraction, probably because the main reason for the shunting is precapillary vasodilatation. Since there are no anatomical porto-pulmonary shunts, surgery is also inappropriate. The only therapy consists of oxygen supplements and low dose diuretics in patients with edema.

Aged↗

In vitro susceptibility of recently isolated respiratory tract pathogens to minocycline and comparable antibiotics. A multicentre study.

The in vitro susceptibility of recently isolated respiratory tract pathogens (217 S. pneumoniae, 202 H. influenzae and 178 M. catarrhalis, has been examined against minocycline, doxycycline, amoxycillin, amoxyclavulanate, cefuroxime, clarithromycin and ciprofloxacin. M. catarrhalis was fully susceptible to all antibiotics except amoxycillin (62% susceptible). H. influenzae showed full susceptibility to minocycline, cefuroxime and ciprofloxacin but different percentages of resistance to the other antibiotics. Among S. pneumoniae isolates resistance was observed to all antibiotics tested between 12% to beta-lactams and 22% to doxycycline.

Adult↗

Antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae from Rwanda, 1984-1990.

A total of 383 clinical isolates of Streptococcus pneumoniae, obtained from an equal number of patients in Kigali, Rwanda, was tested for resistance to penicillin G with a 1 microgram oxacillin disc. Of these isolates, 99 (25.8%) showed reduced zones of inhibition. By means of an agar dilution method, 21% all isolates were confirmed as relatively resistant (MIC > or = 0.12- < or = 1.0 mg/l) strains of Streptococcus pneumoniae (RRSP). A high degree of resistance to penicillin G (MIC > or = 2 mg/l) was not observed. Resistance to chloramphenicol (MIC > or = 8 mg/l) was found in 31% RRSP and in 6% penicillin susceptible strains (PSSP). Doxycycline resistance was common in both RRSP and PSSP strains. All isolates remained fully susceptible to erythromycin. Children more often harboured a strain giving a reduced inhibition zone than did adults (74/230 versus 25/153; P = 0.0005). A total of 32 serotypes or serogroups were identified, seven of them relating to 64.8% all isolates typed. Of all the isolates 84% belonged to a serotype represented in the 23-valent vaccine or to a cross-reacting serotype. Serotype 25, not included in the vaccine, accounted for 10.7% typed isolates from adults but only for 2.0% typed isolates from children. Results of susceptibility testing and clinical experience suggest that penicillin G, ampicillin and chloramphenicol should not be used alone as empirical treatment for pneumococcal meningitis in patients in Rwanda.

Adult↗

[Trends in pneumococcal infections in Belgium from 1986 to 1991].

Streptococcus pneumoniae is one of the most frequent causes of pneumonia, meningitis, and otitis media. Persons at high risk are young children, elderly, and individuals with immunodeficiency or with an underlying disease. Thanks to a network ot 111 laboratories spread all over Belgium, the evolution of the number of deep isolates of S. pneumoniae has been followed from 1986 to 1991: the recorded frequency increased with a mean number of isolations per laboratory and per year rising from 3.6 in 1986 to 6.2 in 1991. The objectives of this paper are to study the evolution of age and sex distribution of the patients, and of the origin of the isolates, and to propose solutions for slowing down this evolution.

Adult↗

Epidemiology and sensitivity of 8625 ICU and hematology/oncology bacterial isolates in Europe. International Study Group.

A multicenter in-vitro study was conducted in 13 countries between May and November, 1992 to determine both the current bacterial epidemiology in Intensive Care and Hematology/Oncology units and the susceptibility of the organisms to cefpirome and other commonly used antibacterials. Eighty-nine hospitals each collected 100 consecutive nonduplicate aerobic clinical isolates from patients in either an Intensive Care (81%) or Hematology/Oncology (19%) unit. The major sources of isolates were respiratory, skin/wound, blood and urine. The MIC of eight different antibiotics was determined using a custom microdilution plate. Predominant bacteria accounting for 80% of the 8625 isolates included: staphylococci (26%); Escherichia coli (17%); Pseudomonas aeruginosa (12%); Klebsiella spp. (10%); Enterobacter spp. (8%) and enterococci (7%). Gram-positive isolates accounted for more than 35% of all isolates. Based on the susceptibility results to the predominant pathogens, the activity of the drugs tested could be categorized into three groups. Cefpirome and imipenem had the most potent in-vitro activity, followed by the third generation cephalosporins cefotaxime, ceftazidime and ceftriaxone, and then piperacillin. The large percentage of Gram-positive bacterial isolates in this patient population indicates the utility of antimicrobial agents that are equally effective against both Gram-positive and Gram-negative organisms.

Anti-Bacterial Agents↗

Evaluation of Bactec high blood volume resin media.

BACTEC PLUS high-blood-volume resin media (aerobic BP 26 vial and anaerobic BP 27 vial) were compared with standard BACTEC media (aerobic NR 6A and anaerobic NR 7A vial). A total of 2253 blood culture sets, each consisting of the four vials, were collected. Positive cultures were obtained from 403 sets and grew 428 organisms; 271 organisms were considered as significant. The BACTEC PLUS high blood volume resin (BP-HBV) media grew significantly more Staphylococcus aureus, coagulase-negative staphylococci, Candida albicans, Enterococcus faecalis, and Pseudomonas aeruginosa. After taking into account the difference of blood volume between the two systems, only S. aureus was significantly more detected by the aerobic BP 26 vial. An enhanced recovery rate with the anaerobic BP 27 vial could not be established. BP-HBV media had an enhanced recovery rate over the standard BACTEC media for S. aureus and C. albicans in patients receiving antibiotics.

Anti-Bacterial Agents↗

Oral cephalosporins.

The arrival of new cephalosporins faces the clinician with an evergrowing confusion as to the drug of choice. The older agents (cephalexin, cephradine, cefadroxil and cefaclor) and the newer formulations cefatrizine and cefuroxime axetil are intensively used for treatment of mild and moderate infections. The oldest agents have a better pharmacokinetic profile but are less active against Gram-positives and Gram-negatives. Cefaclor, cefatrizine and cefuroxime axetil have improved in vitro activity against H. influenzae and/or against S. aureus and M. catarrhalis. However the mean free serum concentrations after proposed standard daily doses of cefaclor (3 x 250 mg/d), cefatrizine (2 x 500 mg/d) and cefuroxime-axetil (2 x 250 mg/d) are lower than those of the older cephalosporins. In comparison amoxicillin-clavulanate is equally efficacious, has a more reliable pharmacokinetic profile and is less expensive than cefaclor and cefuroxime axetil in a comparable dose (e.g. 3 x 500 mg/d).

Administration, Oral↗

Comparative in-vitro activity of RP 59500.

The in-vitro activity of RP 59500 was compared with that of other appropriate antibiotics against 131 staphylococci, 97 streptococci, 20 enterococci, 68 Neisseria spp., 68 Haemophilus influenzae, 21 Moraxella catarrhalis and 250 Gram-negative bacilli. RP 59500 was more active than oxacillin, vancomycin and erythromycin against staphylococci (MIC 0.03-4 mg/L). RP 59500 inhibited streptococci between 0.03-1 mg/L and enterococci between 1-8 mg/L, but was less active than ampicillin and erythromycin. However, its activity remained unchanged against strains with acquired resistance to ampicillin, erythromycin and oxacillin. It was as active as ampicillin against Neisseria spp., but less active against H. influenzae and M. catarrhalis. All enterobacteria and non-fermenters were resistant to RP 59500.

Bacteria↗

New derivatives of kanamycin B obtained by modifications and substitutions in position 6". 1. Synthesis and microbiological evaluation.

The clinical use of the potent, wide-spectrum aminoglycoside antibiotics is limited by oto- and nephrotoxicities. The latter is related to the binding of these polycationic drugs to negatively charged phospholipids and to the subsequent inhibition of lysosomal phospholipases. In order to explore the influence of a modification of the hydrophobic/hydrophilic balance at a specific site of an aminoglycoside, kanamycin B has been chemically modified in position 6" by substitution of the hydroxyl group with a halogen atom (or a pseudohalogen group), or an amino, an amido, a thioalkyl, or an alkoxy group, each series containing increasingly bulkier chains. Examination of the antibacterial activity of the synthesized compounds revealed a negative correlation between the size of the 6"-substituent and the antibacterial activity against kanamycin B sensitive Gram-positive and -negative organisms. Only derivatives with small substituents in position 6", namely chloro, bromo, azido, amino, methylcarbamido, acetamido, methylthio, methylsulfinyl, O-methyl, O-ethyl, and O-isopropyl, showed acceptable activity (geometric mean of minimum inhibitory concentrations for Gram-negative strains less than or equal to 2.5 mg/L; value for kanamycin B, 0.5 mg/L). In vitro toxicological evaluation of all derivatives and computer-aided conformational analysis of selected compounds inserted in a phosphatidylinositol monolayer are presented in the following paper in this issue.

Gram-Negative Bacteria↗

New derivatives of kanamycin B obtained by combined modifications in positions 1 and 6". Synthesis, microbiological properties, and in vitro and computer-aided toxicological evaluation.

Substitution of the C-1 atom in the 2-deoxystreptamine moiety of gentamicin C2, a broad-spectrum aminoglycoside antibiotic, by an axial hydroxymethyl group has been reported to confer protection against most clinically important bacterial enzymes inactivating aminoglycosides, while simultaneously reducing the nephrotoxic potential of this drug. We report here on a similar modification of kanamycin B. Microbiological evaluation, however, revealed no useful protection, as established by the almost complete lack of activity of 1-C-(hydroxymethyl)kanamycin B against an array of organisms producing defined types of aminoglycoside-inactivating enzymes and against which 1-C-(hydroxymethyl)gentamicin C2 and amikacin (1-N-[(S)-2-hydroxy-4-aminobutyryl]kanamycin A) are active. Moreover, toxicological evaluation, based on the in vitro measurement of the drug inhibitory potential toward lysosomal phospholipases, a predictive test of the intrinsic nephrotoxic potential of aminoglycosides, showed not decreased but rather increased toxicity. Comparative conformational analysis of the interactions of the drug with a phosphatidylinositol monolayer explained the lack of protective effect, since no significant change of the mode of insertion of the derivative in this monolayer was detected compared to that of kanamycin B. Combination of a 1-C-(hydroxymethyl) substituent with a 6"-chloro, 6"-acetamido substituent resulted in a partial improvement of the toxicological behavior with no loss of activity for the 6"-chloro and the 6"-azido derivatives, but not to the extent of obtaining better derivatives than kanamycin B itself. We, therefore, suggest that the advantages of an axial hydroxymethyl substituent at C-1 are probably restricted to the gentamicin family and do not extend to kanamycins. It might be concluded that the structural differences between gentamicins and kanamycins play an important, still undescribed role both in their effective recognition by aminoglycoside-inactivating enzymes, which are responsible for most of the clinically important cases of resistance to aminoglycosides, and also in the interactions with phospholipids, which in turn cause nephrotoxicity.

Gram-Positive Bacteria↗

Aztreonam-flucloxacillin double beta-lactam treatment as empirical therapy of serious infections in very elderly patients.

Aztreonam, the first monocyclic beta-lactam antibiotic with pure anti-Gram-negative activity, combined with flucloxacillin, a penicillinase resistant penicillin, was given as empirical treatment of 53 serious infections in very elderly people. Eighteen of the cases had positive blood cultures and 11 had a clinical picture of sepsis without positive blood cultures: Of 49 evaluable infections, 45 (92%) were cured. In 40% of the infections, antibiotic treatment could be narrowed after 72 hours to one antibiotic. Diarrhoea, mostly transitory, was the only side-effect. Aztreonam-flucloxacillin combination is a safe and effective empirical treatment regimen for serious infections in very elderly patients.

Aged↗

Influence of dosage schedule on renal cortical accumulation of amikacin and tobramycin in man.

The pathogenesis of aminoglycoside nephrotoxicity is directly related to the accumulation of drug within the renal cortex. To identify measures that might prevent aminoglycoside nephrotoxicity, we investigated the influence of various dosage regimens on the renal cortical accumulation of amikacin and tobramycin in man. Patients undergoing nephrectomy for a renal tumour with normal renal function and no proteinuria received (i) a single dose of either amikacin (15 mg/kg) or tobramycin (4.5 mg/kg) given iv over 30 min, or (ii) a 24-h continuous infusion of either drug or (iii) amikacin as two injections of 7.5 mg/kg or tobramycin as three injections of 1.5 mg/kg over the 24 h preceding nephrectomy. Serum aminoglycoside pharmacokinetics were examined and renal cortical tissue was sampled for drug determination at operation. A single injection yielded cortical concentrations of 115.4 +/- 21.8 and 68.9 +/- 30.3 mg/kg for amikacin and tobramycin, respectively. Tissue levels after continuous infusion were 171.7 +/- 42.9 and 100.0 +/- 30.0 mg/kg for amikacin and tobramycin, respectively. Two injections of 7.5 mg/kg amikacin resulted in renal cortical concentrations of 196.9 +/- 54.9 and three injections of 1.5 mg/kg tobramycin resulted in renal cortical concentration of 76.5 +/- 18 mg/kg. The AUC for the three dosage regimens was not significantly different for the two aminoglycosides indicating linear serum pharmacokinetics for these drugs. In the case of amikacin, a single injection resulted in significantly lower drug levels than did a continuous infusion or administration of the same dose over three injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Amikacin↗

Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: a case-control study.

We conducted a case-control study in five general hospitals in the region of Antwerp, studying 161 patients (102 men, 59 women) and hospital control subjects matched for age and sex to explore the relation between drug use and upper gastrointestinal bleeding from 'erosive lesions' (peptic oesophagitis, gastric erosions, gastric ulcer(s), or duodenal ulcer(s]. There was a highly significant difference between cases and control subjects in the use of non-steroidal anti-inflammatory drugs (NSAIDs, excluding aspirin) (odds ratio 7.4, p less than 0.001; 95% confidence interval odds ratio 3.7 to 14.7). There also was a significant difference in the use of aspirin (odds ratio 2.2, p = 0.025; 95% CI odds ratio 1.3 to 4.0) and a highly significant difference regarding the presence of antecedents of peptic ulcer disease (odds ratio 5.5, p less than 0.001; 95% CI odds ratio 3.2 to 9.6). There was no significant difference in the use of other drugs, paracetamol and corticosteroids in particular, nor in the use of alcohol or tobacco. The patient group using NSAIDs was older, had more women, and had a higher mortality than the group not using NSAIDs. Among patients with bleeding gastric or duodenal ulcer(s), NSAID users were not more or less likely to have had symptoms of peptic ulcer disease, and had no higher frequency of multiple gastric or duodenal ulcers. The attributable risk for NSAID use was 0.30 (95% CI 0.23 to 0.37) and for aspirin use 0.14 (95% CI 0.08 to 0.20).

Adolescent↗

Incidence of multi-resistance in gram-negative bacterial isolates from intensive care units in Belgium: a surveillance study.

An in vitro study on the prevalence of resistance to major antibiotics in 1,545 Gram-negative aerobic bacilli isolated from intensive care unit patients was undertaken in 16 community and university hospitals in Belgium. A customized dry microtitre panel carrying 16 antimicrobials over an extended concentration range was used for susceptibility testing. The study revealed a widespread resistance to broad-spectrum penicillins, an alarmingly high incidence of resistance to aminoglycosides and a reduced activity of third generation cephalosporins especially in nosocomial pathogens, and a still relatively high susceptibility to imipenem and ciprofloxacin. Wide variations in percentage of resistance to different antibiotics were observed between hospitals, and these differences were not related to type of hospital or number of beds.

Anti-Bacterial Agents↗

First report of chronic meningitis caused by Trichosporon beigelii.

Trichosporon beigelii (Trichosporon cutaneum) was identified as the causative agent of chronic meningitis in a 15-year-old boy with acute lymphocytic leukaemia. After a neutropenic episode following cytostatic treatment and itraconazole therapy as prophylaxis, cerebrospinal fluid (CSF) samples yielded growth of Trichosporon beigelii. Treatment with amphotericin B, flucytosine and high doses of fluconazole was followed by clinical improvement, although CSF pleocytosis remained. The cross-reactivity between Cryptococcus neoformans and Trichosporon beigelii in a cryptococcal antigen latex test was used as a means of diagnosis in CSF and serum samples.

Adolescent↗