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Biomedical subjects

J P Lambert

Publications and source records attributed to J P Lambert.

At least 19 recordsLinked to original sources

Osteoporosis: a new challenge in cystic fibrosis.

The increased life expectancy of patients with cystic fibrosis (CF) may lead to medical complications such as osteoporosis. Based on data collected through a MEDLINE search (1985-May 1999) and review of references for additional relevant articles, nutrition status, weight, and disease severity are factors most highly correlated with osteopenia. Links also were noted with calcium and vitamin D intake, hypogonadism, chronic inflammation, and age, but findings in these areas are not consistent from one report to the next. Increased fracture rates and kyphosis are consequences of osteoporosis. Simple measures such as compliance with recommended nutrition guidelines and restrictions in corticosteroid therapy could be considered first-line management options. Further studies must be conducted to clarify factors involved in the etiology of osteoporosis in patients with CF and to identify the best treatment and prevention methods.

Bone Density↗

Comparison of the acute cardiotoxicity of the antimalarial drug halofantrine in vitro and in vivo in anaesthetized guinea-pigs.

1. Several unrelated drugs have pro-arrhythmic activity associated with an ability to prolong the QT interval of the ECG. The aim of this work was to examine the effects of the antimalarial drug halofantrine in vivo and in vitro. 2. In anaesthetized guinea-pigs consecutive bolus doses of halofantrine (0.3, 1, 3, 10 and 30 mg kg(-1), i.v.) at 25 min intervals caused dose-dependent prolongation of the rate corrected QTc interval and bradycardia. The change in heart rate became significant after administration of 10 mg kg(-1) halofantrine (-23+/-9 beats min[-1]) whereas the increase in QTc was significant with only 1 mg kg(-1) halofantrine (22+/-10 ms). It was only with the highest dose of halofantrine that the PR interval was increased (from 52+/-3 to 67+/-4 ms) and second degree atrioventricular (AV) block (type 1 Mobitz) occurred in all animals. No changes were observed in any parameters in a separate group of guinea-pigs which received vehicle (dimethylacetamide 60% propylene glycol 40%) at equivalent time points. 3. The blood concentrations of halofantrine ranged from 0.26+/-0.17 microM after administration of 0.3 mg kg(-1) to 2.79+/-0.87 microM after 30 mg kg(-1), i.v. There was a significant correlation between the blood concentrations of halofantrine and the changes in QTc interval. 4 In guinea-pig left papillary muscles the effective refractory period was increased significantly 60 min after addition of halofantrine; from 161+/-4 to 173+/-6 ms with 10 microM, 156+/-8 to 174+/-6 ms with 30 microM and 165+/-6 to 179+/-5 ms with 100 microM halofantrine. However, the vehicle (0.1% Tween 80 in DMSO; final concentration of vehicle in Krebs, 1%) also increased the effective refractory period from 164+/-5 to 173+/-6 ms. Similar results were obtained in right ventricular strips but left atrial effective refractory periods were not altered by either the vehicle or halofantrine. 5. The results of these experiments suggest that any direct effects that halofantrine may have had on the effective refractory period of cardiac muscle cannot be separated from those of the vehicle. The prolongation of QTc and consistent observation of AV block with halofantrine in anaesthetized guinea-pigs suggest that in vivo models may be more useful for further studies investigating the mechanisms underlying the cardiotoxicity of halofantrine.

Animals↗

Fine tuning of epitopic dominance induced by lung cancer on the IgG response to bovine betalactoglobulin: towards a paraneoplastic immune marker.

BACKGROUND: Investigating the humoral immune response to mucosal antigens in patients with lung cancer, we have documented a preferential immunoglobulin G (IgG) binding to cryptic epitopes unmasked by the proteolysis of bovine beta-lactoglobulin (BLG). In contrast, IgG from healthy controls and patients with chronic bronchitis (COPD) bind preferentially to continuous epitopes presented on both native (n) and denaturated (d) forms of this antigen. The present study further characterized the differences in the epitope profiles recognized on BLG. METHODS: The capacity of individual sera from 65 lung cancer patients, tested before and after cancer removal for the patients with early stage lung carcinoma, 65 healthy controls, and 52 patients with COPD, to prevent the binding of pooled IgG fractions from each population as well as murine monoclonal antibodies (MoAb), specific for BLG, to solid phase bound antigen was evaluated in enzyme-linked immunoadsorbent assay using streptavidin-biotin technology. Some of these experiments were also performed with sera from 42 patients diagnosed with other cancers. RESULTS: Compared with control sera and sera from patients with other solid tumors, lung cancer patient sera showed distinct capacities to prevent the binding of murine MoAb as well as human pooled IgG fractions to n- and d-BLG. The inhibition capacities of lung cancer sera changed as soon as five weeks after cancer removal. CONCLUSIONS: The results indicate that the difference in epitope specificity exhibited by lung cancer sera is not restricted to cryptic epitopes, but also affects continuous and discontinuous epitopes, accessible only on the native antigen. A high level of binding discrimination between antibodies from the study populations is also observed at the level of the epitope. This deviation in the epitope specificity of antibodies changes soon after cancer removal, suggesting a tumor-dependent disturbance. Also documented in the Dermatophagoides pteronyssinus model, it opens the way to a new class of paraneoplastic immune markers for this malignancy, with, at first glance, a high specificity level.

Adenocarcinoma↗

The value of prescribed 'high-fibre' diets for the treatment of the irritable bowel syndrome.

The symptoms of 72 patients with irritable bowel syndrome were assessed by questionnaire before and 6 months after a high-fibre diet had been prescribed, to find whether those who achieved the highest fibre intake did any better than those with smaller intakes. Dietary fibre intakes were measured after 6 months by a 7-day weighed food inventory. There was a significant inverse association between the presence of symptoms and fibre intake for: incomplete defaecation, urgency and hard stools with total fibre intake; urgency and hard stools with cereal fibre intake; and borborygmi with fibre intake at breakfast. All patients with constipation, mucus, urgency or watery stools at the beginning of the study, and who were consuming more than 30 g fibre by the end, reported an improvement in these symptoms. Increasing intakes of fibre were not related in any way to abdominal distension, diarrhoea, flatulence or patient's feelings about the working of their bowels. Therefore, this study suggests that the symptoms which benefit most from the prescription of a high-fibre diet are hard stools, constipation and urgency.

Adult↗

Effect of a benzoic acid-detergent germicide on denture-borne Candida albicans.

Benzoic acid combined with a detergent was used to safely and effectively decontaminate dentures colonized with Candida albicans. Surface decontamination was accomplished by soaking the dentures in the germicide solution for a period of 6 hours to overnight. Decontamination may occur in as little as 10 minutes when soaking is combined with ultrasonic enhancement.

Benzoates↗

The use of a microcomputer for non-linear optimisation of doses in external radiotherapy.

The study presents software for a microcomputer designed to determine the optimum dose distribution in external radiotherapy, either by calculating the doses delivered and the field width (in linear programming) or, in addition, by calculating the beam geometry (non-linear optimisation). Various optimisation criteria can be selected, namely the homogeneity, the concentration on the target and the total dose in a sensitive area. The article outlines an example.

Humans↗

[Conception of a program for the treatment and statistical interrogation of data, LOGIST].

This paper presents a general program which cannot only be used for the treatment and the statistical interrogations, but also for basic operations, such as the validity check and the preparation of data which is often necessary for other programs. Its use of language is simple, suitable and accessible to non-specialists. The program is sufficiently complete so that it can treat some complex problems without requiring complementary programs. It can treat several problems simultaneously. This allows one to gain data-reading time and the program is therefore economical. Its domain of use is large: epidemiological studies, psychological and sociological investigations, biological studies, clinical research, chronological follow-up, examinations of faculties, . . . . The program is written in FORTRAN IV and thus transferable. It contains more than 25 000 instructions but needs limited place in the core memory (less than 64 000 words). Its structure allows further evolution and addition of new procedures or new methods. A transformation into a conversational form is considered.

Computers↗

Monoclonal antibodies directed against different antigenic determinants of rotavirus.

We have developed a series of monoclonal antibodies against the calf strain RIT 4237 (subgroup 1) and the human strain 82-561 (subgroup 3) of rotavirus, both grown in tissue culture, and also against the human rotavirus 81-2162 (subgroup 2), extracted from a fecal specimen. A variety of different specificities was observed among these antibodies, namely, antibodies against group and subgroup determinants, as well as neutralizing antibodies. By using monoclonal antibodies against the subgroup antigen in an enzyme-linked immunoassay system, the constant predominance of subgroup 2 viruses in humans was confirmed in 74 stools collected from children in Brussels who suffered a diarrheal illness between July 1981 and June 1983. The availability of these antibodies also made it possible to improve the sensitivity and the specificity of the test system.

Animals↗

[The microcomputer in bacteriology. Value in the automated performance of antibiograms in hospitals].

In microbiology, most computerization is carried out by means of important centralized computers. On the contrary, our work is based upon the use of inexpensive microcomputers. We have developed general programs for the acquisition of data, their correction, and retrieval of lists arranged according to desired parameters (hospital department, germ, or sample) and various statistics, especially with respect to germ sensitivity. This system has been used on a routine basis since April 1982 in the Bacteriology Laboratory of Nancy University Hospital. It could easily be adapted to other laboratories and could provide a wide range of essential epidemiological data on the resistance of bacterial strains to antibiotics and their evolution with time.

Computers↗

Prevalence of subgroup 1, 2, and 3 rotaviruses in Belgian children suffering from acute diarrhea (1978-1981).

The relative prevalence of human rotavirus subgroups was studied during a 3-year period (1978-1981) by means of a sensitive complement fixation technique. Among 93 rotavirus isolates from children with acute gastroenteritis in Brussels, the prevalence of subgroups 1, 2, and 3 was, respectively 24, 17, and 32%. The remaining 27% of strains could not be typed, but no evidence for the existence of any new subgroup was found. The proportion of strains belonging to the different subgroups remained roughly constant during the study period, showing the simultaneous occurrence of the various subgroups of viruses, even during the annual winter peak of rotavirus gastroenteritis.

Acute Disease↗

Protection studies in colostrum-deprived piglets of a bovine rotavirus vaccine candidate using human rotavirus strains for challenge.

Studies were performed to evaluate the potential use of the bovine RIT 4237 rotavirus strain as a vaccine candidate against infection with human rotaviruses. Initial experiments revealed that colostrum-deprived piglets were susceptible to infection with several human strains, except for those belonging to subgroup 1. Subsequently, different immunization procedures with RIT 4237 were studied in this animal model. It was found that a two-dose administration, either given intramuscularly (twice) or once intramuscularly and once intragastrically, was necessary to induce a significant serum antibody response. Finally, the protective effect of the latter vaccination schedules against subgroup 2 and 3 rotavirus strains of human origin was evaluated by artificial challenge. In both cases, prior administration of live RIT 4237 significantly decreased fecal shedding of the challenge virus when compared with control animals.

Animals↗

Prevalence of neutralizing antibodies against a candidate rotavirus vaccine in adults.

Because of the morbidity and mortality from infection with rotaviruses in children under 2 years, in many parts of the world but especially in developing countries, an urgent need for a vaccine has been recognized. At present, a vaccine candidate of bovine origin, the RIT 4237 strain vaccine developed from a strain received from Mebus et al., is available. This strain has been shown to induce cross protection by challenge of colostrum deprived piglets with human rotavirus strains. Before testing its protective effect in children, preliminary studies in adult volunteers are required to evaluate its degree attenuation and immunogenicity. With regard to the latter we have studied the antibody profile of 87 healthy adults, ages 25 to 40 years, from whom blood samples were taken between January and June 1982. Antibodies versus RIT 4237 were measured both by neutralization and ELISA techniques. Analysis of the results revealed a significant difference in antibody levels according to sex, since high neutralizing antibody titers (greater than 1:320) were observed about 7 times more frequently in women than in men. Furthermore, no seasonal variation in the level and the distribution of serum antibody titers was found when comparing blood specimens taken from male volunteers in winter and spring. As far as antibody levels obtained by neutralization and ELISA assays is concerned, a good correlations was noted in 75% of cases. However, in 22 out of 87 sera high levels of neutralizing antibodies were found in association with low ELISA antibody titers or vice versa. These results suggest that screening of adult volunteers should be performed by means of a neutralization assay prior to administration of a candidate vaccine. However, in the absence of such preliminary testing, male volunteers should be chosen since there is a higher probability of low pre-existing antibody levels among such subjects.

Adult↗

Software for linear and non-linear optimization in external radiotherapy.

The study presents a set of programs designed to determine optimum dose distribution either by calculation of beam intensities and field width (in linear programming) or, in addition, by calculation of beam geometry (non-linear optimization). Various optimization criteria can be selected: homogeneity, concentration on target, entire dose in a sensitive area. The optimization method used is the gradient projection method, and doses are calculated by Cunningham formulae. The article describes the program operating modes, the main subroutines and their functions and specifications, and outlines an example.

Computers↗

Viricidal capability of resin-triiodide demand-type disinfectant.

Polyoma, Newcastle disease virus, and adenovirus, as well as two coliphages, lambda and T4, were inactivated by strong base quaternary ammonium anion-exchange resin-triiodide. Organic matter interfered with viral inactivation capability of the resin-triiodide. The viruses, as they were being inactivated by the resin disinfectant beads, were not retained or filtered by the beads.

Adenoviruses, Human↗

Enzyme-linked immunosorbent assays adapted for serotyping of human rotavirus strains.

Five enzyme-linked immunosorbent assay systems were adapted for serotyping human rotavirus strains and were compared with a sensitive complement fixation test in terms of specificity and sensitivity. The assays differed mainly with regard to the antibody systems involved in the double sandwich. Serotype differentiation of 34 rotavirus strains was achieved by determining a neutralization endpoint titer, either with a constant antiserum-varying antigen dilution method or vice versa. The procedure which proved to be highly specific and sensitive was one with two type-specific hyperimmune sera (enzyme-linked immunosorbent assay system 5) instead of only one, as in the four other systems.

Animals↗