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Biomedical subjects

P Roux

Publications and source records attributed to P Roux.

At least 19 recordsLinked to original sources

Chest injuries in children: an analysis of 100 cases of blunt chest trauma from motor vehicle accidents.

One hundred twenty-eight cases of chest injury were seen in a Paediatric Trauma Unit over a 5 1/2-year period. One hundred patients sustained motor vehicle accident (MVA)-related blunt chest injuries, 91 of them as pedestrians. Nine children had blunt chest injuries from falls, 10 had stab wounds (3 assault, 7 accidental), and 9 had gunshot injuries (6 from birdshot used by police during civil disturbance). MVA-related injuries were studied separately, as an etiologically homogeneous group. Sixty-five of these patients were under the age of 6. All but 3 also had serious extrathoracic injuries. The mean injury severity score (ISS) in MVA-related injuries was 25. Eight patients died, all with an ISS of 34 or more, 7 of whom had fatal head injuries. In MVA-related injuries, pulmonary contusion (n = 73) was the most frequent lesion seen, followed by rib fracture (n = 62), posttraumatic effusion (n = 58), pneumothorax (n = 38), and pneumatocele (n = 5). In MVA-related injuries, 18 children required ventilation. Thirty-nine (69%) of 56 children with radiologically evident posttraumatic pleural effusion had intercostal chest drainage. Analysis suggests that lung injury is a central event in MVA-related blunt chest trauma. Primary lung injury, radiologically visible as contusion, is complicated by hematoma, posttraumatic effusion, and pneumothorax.

Accidents, Traffic

Long-term expression of the c-fos protein during the in vitro differentiation of cerebellar granule cells induced by potassium or NMDA.

Levels of the c-fos protein were assayed in mouse cerebellar granule cells during their in vitro development under different culture conditions. When grown in media favoring both their survival and differentiation, i.e. in the presence of 30 mM K+ or 12.5 mM K+ plus 100 microM N-methyl-D-aspartate (NMDA), the c-fos protein becomes detectable in the nucleus of granule cells on and after 6 days and persists to high levels until the culture begins to decline. The protein c-fos appears therefore after the critical period described for the survival effect of K+ depolarization or NMDA receptor stimulation which corresponds to days 2-5 after plating. The c-fos protein remains however scarcely detectable or undetectable throughout the life-span of cells cultured under conditions providing poor survival and differentiation, i.e. in the presence of low K+ (5 or 12.5 mM) alone or when the effect of NMDA is blocked by the NMDA receptor antagonist MK-801. Interestingly, in cortical and striatal neurons, the survival and differentiation of which being not affected by depolarizing media, no c-fos protein is detected whatever the culture conditions tested at least during the first 18 days in vitro. This suggests that long-term expression of the c-fos gene might be related to some aspect of the late in vitro differentiation process of cerebellar granule cells.

Animals

The efficiency of cell targeting by recombinant retroviruses depends on the nature of the receptor and the composition of the artificial cell-virus linker.

Using streptavidin-bound antibodies specific for both viral and cell membrane epitopes, we have reported previously that human cells may be infected by murine ecotropic retroviruses through an interaction with major histocompatibility complex class I and class II antigens, and thus have demonstrated that cell targeting by recombinant retroviruses is feasible. We report here that (i) growth factor or hormone receptors, such as those for epidermal growth factor (EGF) and insulin, can also mediate infection of human cells; (ii) a biotinylated cytokine or hormone can substitute for the anti-cell antibody in bispecific antibody complexes, thus extending the versatility of the method; (iii) although yields are low in our assay, infection efficiency clearly appears to depend upon the biochemical composition of molecular bridges because bi-functional antibody complexes are more efficient than cytokine-antibody complexes in the case of the EGF receptor. Finally, our study indicates that different cell membrane molecules are not equally efficient in allowing infection of human cells because targeting of the transferrin, high density lipoprotein and galactose receptors, as well as that of various membrane glycoconjugates, by murine ecotropic retroviruses did not lead to the establishment of a proviral state.

DNA, Recombinant

Evaluation of a monoclonal antibody-based latex agglutination test for diagnosis of cryptococcosis: comparison with two tests using polyclonal antibodies.

Cryptococcal antigen detection has become a routine biological test performed for patients with AIDS. The poor prognosis of cryptococcosis explains the need for reliable tests. We evaluated the performances of a newly commercialized agglutination test that uses a monoclonal antibody specific for cryptococcal capsular polysaccharide (Pastorex Cryptococcus; Sanofi-Diagnostics Pasteur, Marnes-la-Coquette, France) and compared them with those of tests that use polyclonal immune sera (Cryptococcal Antigen Latex Agglutination System, Meridian Diagnostics, Inc., Cincinnati, Ohio; and Crypto-LA, International Biological Labs Inc., Cranbury, N.J.). The sensitivities and specificities of the tests were compared by using purified polysaccharides and yeast suspensions. Clinical specimens (131 serum samples, 41 cerebrospinal fluid samples, 34 urine samples, and 19 bronchoalveolar lavage samples) from 87 human immunodeficiency virus-positive subjects with (40 patients) and without (47 patients) culture-proven cryptococcosis were retrospectively tested during a blinded study. The effect of pronase treatment of samples was assessed for Pastorex Cryptococcus and the Cryptococcal Antigen Latex Agglutination System, and the antigen titers were compared. Our results show that (i) during the screening, concordance among the three tests was 97%; (ii) the use of pronase enhanced both the sensitivities and specificities of the Pastorex Cryptococcus test; (iii) titers agreed for 67% of the cerebrospinal fluid samples and 60% of the serum samples; and (iv) cryptococcosis was detected equally well with Pastorex Cryptococcus and with the other tests, whatever the infecting serotype (A, B, or D). The meaning of in vitro sensitivity and the relationship between titers and sensitivity are discussed. The results show that Pastorex Cryptococcus is a rapid and reliable test for the detection of cryptococcal antigen in body fluids and suggest that kits cannot be used interchangeably to monitor antigen titers in patients.

AIDS-Related Opportunistic Infections

[Acute respiratory insufficiency caused by hyperinfestation with strongyloides. BALF diagnosis and favourable outcome].

Hyperinfestation with Strongyloides is a severe complication in immunodepressed patients. It may present with various clinical signs, notably acute respiratory failure. Diagnosis may be difficult, particularly when the strongyloidiasis is associated with septicaemia caused by Gram-negative organisms. We report a new case of hyperinfestation with Strongyloides in a patient treated for periarteritis nodosa. This case was remarkable on two scores: the diagnosis problem raised by the presence of intrapulmonary haemorrhages, and the favourable outcome of an acute and initially severe respiratory failure which had required assisted ventilation. The role played in the patient's cure by the doses of thiabendazole given and the duration of their administration is discussed.

Acute Disease

Cell targeting by murine recombinant retroviruses.

Cell targeting by murine retroviruses carrying recombinant genes would have numerous applications such as immortalization of under-represented cell types from complex cellular mixtures, increasing therapeutical yields in the case of gene therapy and delivery of specific genes at any location and at any moment of the life-time of living animals. To this aim, we are currently developing techniques that allow binding of viral particles to specific cell membrane markers different from the natural receptors. We have shown that biochemical bi-specific molecular adaptors able to bind both viral particles and cell surface molecules may reveal appropriate for piloting viruses toward specific cell types. More recently, we have undertaken the genetic engineering of the retroviral envelope glycoprotein in order to modify its natural tropism. This approach is discussed below.

Defective Viruses

Bed use in the medical wards of Red Cross War Memorial Children's Hospital, Cape Town.

OBJECTIVE: To determine extent of appropriate (medically necessary) and inappropriate bed use and level of care (LOC) needed by patients admitted to hospital. DESIGN: A cross-sectional, descriptive survey. SETTING: Medical wards of Red Cross War Memorial Children's Hospital (RCCH), a teaching hospital of the University of Cape Town. MEASUREMENT AND RESULTS: A 25% sample of beds was selected randomly each day for 12 consecutive days during September-October 1990. Data were collected using a questionnaire based on the Pediatric Appropriateness Evaluation Protocol and the Delay Tool. A subjective measure of LOC was developed. Questionnaires were completed for 171 admissions and 365 patient days; 98% of admissions and 79.5% of patient days were medically justified, and 49% of admissions needed tertiary care. The remaining 51% could have been treated by general paediatricians (17%) or medical officers (32%) in community hospitals. Of delays (unnecessary patient days) 62% were hospital-related, 20% were family-related and 18% were related to inadequate lower level institutional care and outpatient services. CONCLUSION: RCCH is functioning as a general, specialist and super-specialist hospital. Its future role as a tertiary referral centre will depend on adequate provision of community-based care. Further cost-benefit research is needed to address areas of inappropriate bed use identified in this study.

Bed Occupancy

Retrovirus-mediated gene transfer of a human c-fos cDNA into mouse bone marrow stromal cells.

A cDNA encoding a complete human c-fos protein was isolated and inserted into two different murine MoMuLV-derived recombinant retroviruses allowing expression of c-fos protein in different cell types. One c-fos-expressing retrovirus, chosen for its ability to express high levels of proteins in fibroblast-like cells, was shown to potentiate long-term cultures of mouse bone marrow stromal cells in vitro and therefore constitutes a potential tool for immortalizing such cells. Moreover, when tested in an in vitro differentiation assay, stromal cells constitutively expressing c-fos favor the granulocyte differentiation of hematopoietic precursors. Interestingly, retroviruses expressing v-src and v-abl oncogenes, included as controls in our experiments, do not produce any detectable effects, whereas those expressing polyoma virus middle T antigen facilitate long-term growth in vitro of stromal cells that favor the macrophage differentiation pathway of bone marrow stem cells. Our observation supports the idea that constitutive expression of some oncogenes, including c-fos and polyoma virus middle T antigen, may influence cytokine production by bone marrow stromal cells.

Animals

[Clinical use of morphine derivatives in neuro-anesthesia].

Narcotics are used in neuro-anesthesiology according to their pharmacology and their effects on cerebral physiology. New narcotics (fentanyl, sufentanil, alfentanil) fulfill the requirements of modern neurosurgical anesthesiology looking for quick awakening.

Analgesics, Opioid

[Anesthesia for treatment of intracranial aneurysm: propofol-alfentanil combination].

Propofol combined with Alfentanil was used for intracranial aneurysm surgery in 145 patients. These anaesthetic agents prevent blood pressure increase. They facilitate induced hypotension. The effect upon intracranial pressure is moderate. This technique is versatile. The speedy awakening make the postoperative neurological supervision easier.

Adolescent

[Treatment of pneumocystosis: preclinical evaluation].

There are now three methods to evaluate treatments of pneumocystosis: (1) the animal model, using adult rats under corticosteroids; the intensity of infection is assessed on pulmonary appositions and can then be evaluated after administration of a potential treatment compared with a reference; (2) the in vitro propagation of P. carinii observed from rat lung extracts cultured on cell lines; this method, however, is limited by the difficulties encountered in quantifying the parasitic types; (3) the inhibition by the drugs tested of enzymes involved in folate synthesis is a method that is still under evaluation. The animal model remains the reference method.

Animals

Nuclear localization of c-Fos, but not v-Fos proteins, is controlled by extracellular signals.

We report here that transport of the protein product of the c-fos proto-oncogene from the cytoplasm, where it is synthesized, into the nucleus, where it operates as part of the AP-1 transcription complex, is not spontaneous but depends on the continuous stimulation of cells by serum factors. A labile protein inhibitor of transport, the effect of which is reversed by cAMP, is responsible for retention of c-Fos protein within the cytoplasm of serum-starved fibroblasts. In contrast, v-Fos proteins transduced by the murine retroviruses FBJ and FBR, which remain nuclear in the absence of serum, evade the translocation control, which therefore appears to contribute to their tumorigenic potential.

Animals

MoMuLV-derived self-inactivating retroviral vectors possessing multiple cloning sites and expressing the resistance to either G418 or hygromycin B.

To facilitate cloning procedures in recombinant murine leukemia virus-derived retroviruses, we have constructed vectors that both carry a polylinker with multiple restriction sites and express resistance to either G418 or hygromycin B. Our vectors are self-inactivating retroviruses that suppress interferences between LTR enhancers and internal promoters and avoid transcriptional stimulation of host cell genes. They can also be used as expression vectors in direct transfection assays, since no translation initiation codon lies between the 5' LTR and the cloning polylinker.

Base Sequence

Severe disseminated staphylococcal disease associated with osteitis and septic arthritis.

We reviewed the records of 1,156 patients treated for acute staphylococcal osteitis or septic arthritis over a 12-year period; 38 had been critically ill with evidence of multiple-organ involvement and 30 (79%) had features of the toxic shock syndrome. The mortality rate of these 38 patients was 13% and the long-term orthopaedic complication rate was 39%. The diagnosis and management of patients with osteitis or septic arthritis, disseminated staphylococcal disease, and the toxic shock syndrome is discussed.

Acute Disease