Biomedical subjects
Publications and source records attributed to M Robin.
The (1)H and (13)C NMR resonances for forty-three 2-aryl and 2-N-arylamino benzothiazole derivatives were completely assigned using a concerted application of one- and two-dimensional experiments (DEPT, gs-COSY, gs-HMQC and gs-HMBC).
We report long-term outcome in 102 patients with cCML transplanted from an HLA-identical sibling donor from 1982 to 1998. The conditioning regimen was based on cyclophosphamide associated with either total body irradiation (TBI) (37 patients) or with busulfan (63 patients). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporin and methotrexate in the majority of the patients. Fifteen year overall survival was estimated at 53% (95% confidence interval (CI), 44-65) with a plateau after 2.5 years. Long-term survival was adversely affected by: longer time from chronic myeloid leukemia (CML) diagnosis to transplantation, older age at time of transplantation and GvHD (acute grade III-IV or chronic extensive). The main cause of death was infection, related to GvHD in 69% of patients. Splenectomy also significantly increased the risk of bacterial infection. 15-year relapse was estimated at 8% (95% CI, 0.1-14). Late malignancies occurred in seven patients, four of whom had an invasive cancer. Other frequent late complications included cataracts, psychological depression, osteonecrosis and hypothyroidism. These complications were more frequent following splenectomy, TBI and in patients with chronic extensive GvHD. We conclude that allogeneic transplantation with a related donor can cure more than half of CML patients in chronic phase, although physicians should be alert to long-term complications.
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Malaria is a major health concern particularly in Africa which has about 90% of the worldwide annual clinical cases. The increasing number of drug-resistant Plasmodium falciparum justifies the search for new drugs in this field. Antimalarial activity of 2-substituted 6-nitro- and 6-amino-benzothiazoles and their anthranilic acids has been tested. An in vitro study has been performed on W2 and 3D7 strains of P. falciparum and on clinical isolates from malaria-infected patients. Toxicity has been assessed on THP1 human monocytic cells. For the most active drug candidates, the in vitro study was followed by in vivo assays on P. berghei-infected mice and by in vitro assays in order to determine the stage-dependency and the mechanism of action. Of 39 derivatives tested in vitro, 2 had specific antimalarial properties. Each compound was active on all stages of the parasite, but one was markedly active on mature schizonts, while the other was more active on young schizont forms. Both drugs were also active on mitochondrial membrane potential. In vivo data confirmed efficiency with a sustained decrease of parasitaemia. Products A12 and C7 may be considered as potential antimalarial worthy of further chemical and biological research.
In this single-centre retrospective study, we analysed risk factors for nonrelapse long-term morbidity and mortality in patients with acute myeloblastic leukaemia (AML) who had undergone allogeneic transplantation. A total of 112 patients with de novo AML in first complete remission (CR1), n=90 or second complete remission (CR2, n=22) who received un-manipulated bone marrow grafts from human leukocyte antigen identical siblings between January 1985 and August 2000 were included. Of these, 97 patients alive and disease-free for at least 100 days after transplant were selected for the purpose of this long-term analysis. The use of an intensified conditioning regimen, Gram-negative bacteriaemia before transplantation, year of transplantation and number of pretransplant chemotherapy courses for patients in CR1 significantly affected the 7-year event-free survival which was 57%. 7-year transplant-related mortality TRM was 22%. Significant predictors for TRM were: bacterial infections before transplantation, major ABO blood group incompatibility, late severe bacterial infections, and chronic (graft-versus-host disease) GvHD. Predictive factors for late severe bacterial infections were infections before transplant, total body irradiation and GvHD. Incidence and risk factors for other late events including, chronic GvHD, late infections, osteonecrosis, cataract, endocrine- cardiac- and lung-complications, cancer and performance status at last follow-up were also studied. The analysis strongly suggests that the combination of pretransplant factors such as chemotherapy and conditioning, and posttransplant factors such as chronic GvHD had a major impact on late nonrelapse morbidity and mortality.
There are few data on Pneumocystis carinii pneumonia (PCP) in critically ill human immunodeficiency virus (HIV)-negative patients. Improved knowledge of the presenting symptoms of and prognostic factors for PCP may help to reduce the high mortality rate associated with PCP in such patients. We retrospectively studied 39 consecutive patients with acute PCP-related respiratory failure and malignancy who were treated at 2 intensive care units (ICUs) during a 10-year period. Univariate logistic regression identified the following 8 predictors of mortality at 30 days after patient admission to the ICU (30-day mortality rate, 33%): complete remission of the malignancy (odds ratio [OR], 0.18), receipt of >1 course of antimalignancy chemotherapy (OR, 17.2), involvement of 4 lobes noted on a chest radiograph (OR, 5), >15% neutrophils in bronchoalveolar lavage [BAL] fluid specimens (OR, 6), Organ System Failure score (OR, 7.33), Simplified Acute Physiology Score II (OR, 1.12), and the need for either mechanical ventilation (OR, 63) or vasopressors (OR, 25.9). Studies are needed to determine whether aggressive monitoring and treatment of patients with >15% neutrophils in BAL fluid specimens can improve the outcome of critically ill patients with malignancy and PCP.
Since the 16-kDa bronchiolar Clara cell protein (CC16) and the alveolar surfactant-associated proteins (SP)-A and -B leak into the circulation when parenchymal health is disturbed, the aim of this study was to determine whether their serum levels could serve as early peripheral markers of tobacco smoke-induced epithelial injury. Sixty-nine (51 yrs (32-54) median (25-75th percentile)) nonsmokers and 54 (42 yrs (31-53)) asymptomatic smokers were enrolled in the study. Serum levels of SP-A did not differ between subjects (270 (208-389) versus 259 (168-392) microg x L(-1)), however, CC16 levels decreased (10.6 (8.7-14.6) versus 7.6 (6.0-11.2) microg x L(-1)) and SP-B levels increased (2,529 (2,091-2,943) versus 3,053 (2,613-4,188) microg x L(-1)) in the smokers. When tobacco smoke exposure, serum creatinine (renal index), age and sex were used as independent variables, CC16 was negatively influenced by cumulative smoking and positively influenced by age. SP-A and -B were negatively influenced by creatinine and positively influenced by cumulative smoking. Serum SP-B was inversely correlated with forced expiratory volume in one second/vital capacity, suggesting an association between obstructive disease and parenchymal lung health. The authors suggest that serum surfactant-associated proteins-A and -B reflect increased alveolocapillary leakage whereas Clara cell secretory protein 16 reflects tobacco smoke-induced Clara cell toxicity. Their evaluation may allow the effects of tobacco smoke on different levels of the respiratory tract, cellular toxicity and epithelial leakage to be distinguished.
Bourneville's disease, first described in 1862, is a phacomatosis that is either autosomal dominant or sporadic. Its typical clinical signs include mental retardation, epilepsy and cutaneous adenomas. The pulmonary form is rare, less than 1%, and is secondary to occlusion of the bronchus, vascular and lymphatics by immature smooth muscle cells. Chylothorax may appear in more than 50% of all cases. No guidelines currently exist for treatment of recurrent chylothorax. However, several possibilities are described in the literature.
S21400 (AERODIOL) is a new intranasal formulation of 17beta-estradiol. It provides a pulsed estrogen therapy that ensures sufficient estrogenisation of tissues to treat estrogen deficiency symptoms, particularly those of the menopause. This multicentric study was designed to determine dose-range, efficacy and acceptability of S21400. One hundred and thirty four women were allocated a daily dose of 100-900 microg for 12 weeks. The doses of 100, 600 and 900 microg were given in two daily administrations, the doses of 200, 300 and 450 microg were given in one and two daily administrations. Oral progestogen was added the last 10-14 days of each cycle of estrogen therapy in all non-hysterectomized women. S21400 showed a dose-effect relationship and provided adequate estrogenisation in more than 80% of patients receiving a dose ranging from 200 to 600 microg daily. Hormonal impregnation was judged sufficient in 23% of women receiving the lowest dose (100 microg). It was often considered excessive for daily doses of 900 microg (36%). After 12 weeks of treatment, efficacy was similar whether the total daily dose was given in one or two administrations. Treatment was well tolerated and accepted, with only minor nasal events (prickling, sneezing). It was perceived by 92% of patients as good or excellent and 81% chose to continue the nasal treatment when it was offered to them. An initial dose of 300 microg per day provides an optimal efficacy/tolerability ratio. In summary, the pulsed estrogen therapy with AERODIOL in one daily administration offers a safe, well accepted and highly effective treatment to alleviate climacteric symptoms. It can be adapted easily to ensure optimal clinical efficacy.
To determine the effect of exercise on serum levels of Clara cell protein (CC16) and surfactant-associated protein A (SP-A), serum was collected from 14 healthy subjects 1 h after maximal and sub-maximal exercise. Healthy volunteers participated on separate occasions in a control (no exercise) session, simulated firefighting tasks for 30 min (n=14), and intermittent treadmill exercise at near maximal heart rates for 60 min (n=10). Serum samples and induced sputum samples were collected 1 h post exercise. Induced sputum fluid was analyzed for tumor necrosis factor alpha (TNF-alpha), an inflammatory mediator produced by pulmonary macrophages. Serum CC16 levels increased significantly with both firefighting tasks (15+/-13 microg/L vs. 9+/-4 microg/L, P=0.047) and treadmill exercise (15+/-8 microg/L vs. 9+/-4 microg/L, P<0.01). Serum SP-A concentrations did not change compared to control with either firefighting tasks (247+/-106 microg/L vs. 247+/-96 microg/L, P=0.84) or treadmill exercise (251+/-89 microg/L vs. 285+/-87 microg/L, P=0.44). TNF-alpha concentrations in sputum supernatant showed no significant difference from controls. These results show an increase in serum CC16 after exercise. This must be considered when utilizing serum CC16 to determine the presence of lung injury in settings that combine exercise and toxic exposures.
The bronchiolar 16 kD Clara cell secretory protein (CC16) and the alveolar surfactant-associated protein A (SP-A) are secreted in the amniotic fluid (AF), where they reflect the growth and the maturity of the fetal lung. To evaluate the possible effects of in utero tobacco smoke exposure upon infant bronchoalveolar epithelium function and maturity, CC16 and SP-A levels were determined in AF obtained at term (36-41 wk) from 28 nonsmoking, 18 smoke-exposed, and 28 smoking mothers with uncomplicated pregnancies. Tobacco smoke exposure was assessed by questionnaire and the assay in AF and maternal urine of cotinine, a stable nicotine metabolite. The specificity of the changes of CC16 and SP-A concentrations in AF was assessed by comparison with nonpulmonary proteins of high- (albumin and transferrin) or low-molecular weight (beta2-microglobulin, retinol binding protein, cystatin-C). Pulmonary and nonpulmonary AF proteins were also compared by two-dimensional gel electrophoresis between smoking and nonsmoking mothers. The levels of CC16 and SP-A as well as low- and high-molecular-weight proteins were not significantly different between the three smoking categories. The protein pattern of AF, established by two-dimensional gel electrophoresis, did not reveal any quantitative or qualitative difference between nonsmoking (n = 10), smoke-exposed (n = 5), and smoking mothers (n = 5). By multiple regression analysis of possible determinants, tobacco smoke did not emerge as a significant predictor of CC16 and SP-A concentrations in AF. SP-A level was dependent only on gestational age at birth (r2 = 0.1, p = 0.001), whereas CC16 correlated only with the levels of low-molecular weight proteins (r2 = 0.2, p = 0.0001). The latter correlation suggests that CC16 enters AF not only as a result of its secretion at the surface of the respiratory tract but also partly following its elimination by the fetal kidney. This study suggests that maternal smoking during pregnancy is not associated with alterations of the secretory functions of the epithelium of the distal airways and the alveoli at term.
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We report the case of a patient with insulin-requiring type 2 diabetes who exhibited a rapid deterioration of his renal function leading to haemodialysis in a few months. Various diagnosis were considered to explain this rapid deterioration, excluding diabetic nephropathy as major etiology. The exploration, especially renal biopsy, demonstrated the presence of a glomerulonephritis due to the deposition of immune complexes associated to active hepatitis C rather than diabetic glomerulosclerosis. A treatment with interferon-alpha allowed to partially restore renal function, this recovery permitting the interruption of hemodialysis, with a current follow-up of more than 6 months.
Human angiogenin is a member of the pancreatic ribonuclease superfamily that induces blood vessel formation. Its three-dimensional solution structure has been determined to high resolution by heteronuclear NMR spectroscopy. 30 structures were calculated, based on a total of 1441 assigned NOE correlations, 64 coupling constants and 50 hydrogen bonds. The backbone atomic rms difference from the mean coordinates is 0.067 +/- 0.012 nm and 0.13 nm from the previously determined crystal structure. The side-chain of Gln117 was found to obstruct the active site as observed in the crystal state. There was no evidence of an alternative open form of angiogenin, although two sets of chemical shifts were observed for some residues, mainly around the active site and in the C-terminal segment. The topology of the ribonucleolytic active site is described with a particular emphasis on the conformation and protonation of active-site His residues. The side-chain of His114 adopts two main conformations in solution. In contrast to pancreatic ribonuclease A, His13 was shown to be more basic than His114, with pKa values of 6.65 and 6.05 respectively. The His47 residue is located in an environment very resistant to protonation with a pKa lower than 4.
This study aims to describe the ways in which mothers of twins organize their childcare activities during the first year after a twin birth and to determine what factors might affect these mothering practices. The mother's physical and psychological state, support and help from the father and others in the surroundings, and the type of twinship were among the factors studied. Data on the organization of feeding, sleeping and waking routines were gathered from 51 families. A correspondence analysis and a cluster analysis showed that twin mothering practices can be described along two dimensions: individualized care vs collective care, and level of organization of daily routines. The mother's state of fatigue only partially accounts for the different types of maternal behavior. Likewise, the presence of several caregivers does not lead to greater individualization in care routines. Nor does there seem to be a clear link between the type of maternal behaviour and the type of twinship. The discussion deals with the mother's emotional investment, her personal capacity for adjusting to the "triadic motherhood' process, and the nature of the father's involvement in that process. Another consideration is the impact of the type of childcare pattern on twin development.
Epidural opioids for caesarean section are routinely used by many anaesthesists. Combined epidural injection of a local anaesthetic and an opioid provides a more rapid onset of profound analgesia. No side effects are observed in either the mother or the neonate with epidural "microdoses" of sufentanil or fentanyl, but the postoperative analgesia is of short duration. Combined intrathecal injection on 0.1-0.2 mg morphine and 0.5% hyperbaric bupivacaine provides a better intra- and postoperative analgesia. Opiates used during anaesthesia in toxemic women before delivery imply strict subsequent paediatric care. Good postoperative analgesia can be obtained with intrathecal morphine or patient-controlled analgesia. Using other techniques depends on care and surveillance facilities. Opiates by spinal or intravenous route are not dangerous for breast-fed newborns.
BACKGROUND: Mothers of twins have some difficulties to individualize their child-raising activities during the first year. This study was aimed to determine factors influencing such activities. POPULATION AND METHODS: Thirty-seven pairs of twins born after 36 weeks of gestation and weighing more than 2,000 g were included in the study. Relationships between the parents and their children were studied from questionnaires concerning activities during the first trimester and the end of the first year of age. Each item concerning organization of meals and sleeping was graded 1 to 3 according to the degree of individualization of the care. Items concerning support of the mother by the father or other people were graded 1 to 3 according to the degree of this assistance. The physical and psychological status of the mother was also graded according to the presence or not of asthenia and/or depression. Home activities of the mother were also observed. RESULTS: The state of the mother during the first few months had an impact on her mothering behavior: tired or depressed mothers tend to treat the twins collectively and simultaneously. No link was found between social, paternal or general familial support and the degree of individualization in the maternal behaviors. CONCLUSIONS: Several factors can interfere with the psychological repercussions of a twin birth on the mother and subsequent psychoemotional development of children. Further studies are necessary to understand how each parent contributes to the organization of the family system.