Revisiting statistical methods to assess the effect of hematopoietic inhibitors using colony-forming assays.
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Animals↗
Biomedical subjects
D Bonnet
Publications and source records attributed to D Bonnet.
[Giant cell tumor. Apropos of a costovertebral site].
The authors report a case of giant cell tumor. This case was unusual by its location (rib and vertebra), its size and its important inner thorax extension. This tumor was studied with different imaging methods and particularly MRI. The sensitivity of MRI is confirmed by the surgery in complete agreement with MRI findings.
Adult↗
Comparison of the effect of two prazepam formulations on psychomotor and cognitive function in healthy volunteers.
A double-blind crossover design was used to evaluate the effect of two different formulations of prazepam, on motor and cognitive functions and subjective symptoms. Ten healthy male volunteers received 20 mg of prazepam both in tablet and liquid (as drops) formulation, separated by a 1 week interval. All subjects completed a battery of 9 performance tests 2.25 h and 4.75 h after drug intake (corresponding to the times of peak plasma concentration). They also rated themselves on eight visual analogue scales before, 2 h, 4.5 h and 8 h following drug intake. A significant difference between liquid drops and tablets was demonstrated in 4 of the 9 performance tests and 2 of the 8 items of the self rating scales. These results suggest that a single dose of prazepam administered in liquid drop form exhibits greater sedative properties than the same dose administered as tablets in healthy volunteers, probably as a result of more rapid absorption.
Chemistry, Pharmaceutical↗
Rous sarcoma virus expression in Saccharomyces cerevisiae: processing and membrane targeting of the gag gene product.
In avian cells, the product of the gag gene of Rous sarcoma virus, Pr76gag, has been shown to be targeted to the plasma membrane, to form virus particles, and then to be processed into mature viral gag proteins. To explore how these phenomena may be dependent upon cellular (host) factors, we expressed the Rous sarcoma virus gag gene in a lower eucaryote, Saccharomyces cerevisiae, and studied the behavior of the gag gene product. We show here that Pr76gag is processed in yeast cells and that this processing is specific, since it is abolished in a mutant in which the active site of the gag protease has been destroyed. In this mutant, the uncleaved precursor is found associated with the yeast plasma membrane, yet no virus particles were detected in cells or in the culture medium. From our results, we can speculate either that in yeast cells, a host protease initiates Pr76gag processing in the cytosol or that in avian cells, an inhibitor prevents the processing until the viral particle is formed.
Avian Sarcoma Viruses↗
[Incessant idiopathic ventricular tachycardia in infants].
Reduction of the arrhythmia was obtained in 1 to 5 days, spontaneously (2 cases) of after oral amiodarone (500 to 2000 mg/m2/24 hr) (5 cases) or intravenous flecainide or propafenone in the two most critically ill patients. With the exception of 1 patient who was successfully treated with propranolol for 1 year, amiodarone was prescribed in all cases for 7 to 36 months after reversion to sinus rhythm: 5 children have been taken off treatment and seem to be completely cured 4 to 9 years after withdrawal; the other 3 patients have not had recurrences but have only been treated for 6 to 15 months. One of them has neurological sequellae from a cerebral embolism originating from an atrial thrombus. These results show that incessant ventricular tachycardia in infancy is a serious condition but amenable to medical treatment with high dose amiodarone or, when poorly tolerated, intravenous Class 1c antiarrhythmics for reduction of the arrhythmia, and amiodarone at adequate doses for 2 years to prevent recurrence. With the exception of the rare arrhythmogenic right ventricular dysplasia, the long term prognosis would seem to be excellent and, in general, there would seem to be little need for surgery.
Amiodarone↗
Inhibition of human bone marrow progenitors by the synthetic tetrapeptide AcSDKP.
The purpose of this work was to study the effects of a tetrapeptide, acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of spleen colony-forming unit (CFU-S) entry into DNA synthesis, on human progenitor cells. Normal human mononuclear cells were incubated with concentrations of the synthetic tetrapeptide ranging from 10(-12) to 10(-7) M for 1.5 and 24 h and then plated in methylcellulose in the presence of human placenta-conditioned medium and recombinant human erythropoietin. The proportion of progenitors in DNA synthesis was determined by the thymidine suicide assay. Incubation with AcSDKP for 24 h leads to a significant inhibition of granulocyte-macrophage colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) growth and in some cases of erythroid colony-forming unit (CFU-E) growth. The inhibition, which was never greater than 50%, was obtained with 10(-10)-10(-9) M AcSDKP, whereas no effect was seen at higher concentrations. The percentage of CFU-GM, BFU-E, and CFU-E in DNA synthesis was significantly reduced in five consecutive patients after incubation of cells for 24 h with inhibitory doses of the peptide, indicating that it is active on cycling cells. Therefore, these studies provide the first evidence that the tetrapeptide AcSDKP, originally obtained from bovine marrow and now chemically synthesized, is able to inhibit the in vitro growth of human progenitors and to decrease their proportion in cell cycle.
Amino Acid Sequence↗
[Partial atrioventricular block and prolonged QT interval in 4 premature infants receiving diphemanil].
Four premature infants presenting with episodes of bradycardia in the first weeks of life were given diphemanil. One of them received an overdose accidentally. Paradoxically, this induced a permanent bradycardia leading to the discovery of a grade II A-V block as well as a prolonged QT interval. Discontinuation of the drug resulted in a prompt normalization of these changes. It is felt that this anticholinergic therapy may have caused a prolongation of the QT interval and, therefore, a partial A-V block in case of sinus tachycardia. Thus, such a therapy should not be given to young premature infants without having checked the QT interval on a ECG tracing and having made sure that it is adapted to the actual heart rate. It is also advised to reduce usual doses.
Bradycardia↗
Expression of HIV antigens at the surface of infected T4 cells: immunoelectron microscopic evidence of an immunogenic phase prior to the viral release.
HIV antigens were detected by immunoelectron microscopy at the surface of human and simian T4 lymphocytes that had been infected in vitro. HIV antigens were detected at the surface of cells exhibiting viral particles but also at the surface of cells before the release of virions. The latter cells may be considered immunogenic since they are capable of triggering specific immune responses without the cytopathic effects due to viral release.
Animals↗
Adult and paediatric AIDS patients lacking HIV antibodies detected by enzyme immunoassay in central Africa: further serological studies.
We describe HIV antigen and HIV-1, HIV-2 and human T-cell leukaemia virus type I (HTLV-I) Western blot (WB) results in 20 adults and 12 children with AIDS who were shown to be HIV-1 seronegative by two commercial enzyme immunoassays (EIA), in Kigali, Rwanda, central Africa. These patients represented 3% of adults and 7.4% of children with AIDS observed in Kigali during the study period. Thirteen of the adults and five of the children were HIV-1 WB positive. All patients were HTLV-I WB negative. One adult AIDS patient had a reactive HIV-2 WB; he is the first HIV-2-infected individual to be diagnosed in Rwanda. HIV antigenaemia was demonstrated in only one adult and one child, suggesting that HIV antigenaemia is not frequent in African AIDS patients, even in the case of weak immunologic responses to HIV core proteins. Three adults and four children had none of the serological markers detected. This study showed that HIV EIA negativity occurs infrequently in African patients with AIDS. In such a situation, an attempt to detect HIV antibodies by a more sensitive technique, such as WB, is necessary.
Acquired Immunodeficiency Syndrome↗
[Severe forms of effort-induced asthma].
Severe reactions in exercise-induced asthma (EIA) seem to be underestimated in the published literature. We report two cases of near-miss death from EIA that occurred after a short run. We review 364 exercise tests that were performed between September 1987 and October 1988 by a standardised protocol on a treadmill, on patients with possible EIA. A positive test, defined by a fall of FEV1 of at least 20% was found in 173 patients. From 21 patients with a fall of greater than 50%, 4 presented severe signs of: Cyanosis. Intense dyspnea with impediment of speech. General malaise with hypertension. These 4 patients were not greatly different from patients of the 50% fall group when compared for FEV1 before the test and for heart-rate during the test. They differed in the duration of the asthma attack, which was more protracted, despite the use of beta-2 agonists. The onset of severe reactions is 2.3% of positive tests and seems to be unpredictable.
Adult↗
[Perception of malaria in Africa south of the Sahara].
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Burkina Faso↗
[Geographical distribution and pathogenesis of chronic calcifying pancreatitis in tropical zones. Results of a multicenter survey in French-speaking Black Africa].
Chronic calcifying pancreatitis (CCP) is rare in countries with low alcohol consumption except in some tropical countries where malnutrition is widespread (southwest India) and in which CCP occurs in young non-alcoholics. In Black Africa sporadic cases of CCP have been reported in English-speaking countries (Uganda, Nigeria). The purpose of this study was to: a) assess the geographical distribution of CCP in French-speaking Africa; b) estimate the relative proportion of alcoholic CCP (ACCP) and juvenile tropical pancreatitis (JCCP). A total of 92 cases were included in this study, conducted in 16 French-speaking African countries (including Madagascar). There were no cases in countries with partly desert to climates and Moslem populations. Of these 92 cases, 86 corresponded to ACCP due to over consumption of various types of alcoholic beverages depending on the region. All were males with a mean age at diagnosis of 40.7 yrs. The remaining 6 cases were JCCP which were observed in areas of malnutrition with low intakes of animal protein and lipids. In this group the male/female ratio was 1/1 and the mean age at discovery was 15 yrs. Manioc toxicity did not appear to play any role. The "mixed" form, i.e. associating current alcohol consumption with childhood malnutrition, which has been described in young moderate drinkers in Burundi, was a possibility in 4 of the 86 cases of ACCP.
Adolescent↗
[Construction and preliminary validation of an anxiety scale, the FARD (Ferreri anxiety rating diagram)].
The complexity of the anxious disease does not facilitate the clinical approach. That the reason why the authors have developed a rating scale based on a descriptive symptomatology to find out a diagnosis, to rate the severity of illness and to facilitate the pharmaceutical prescription. To develop a skill needed by general practitioners as well as specialists, Prof. M. Ferreri worked with pools of medical doctors to isolate the more frequent items in the anxious symptomatology. So they pointed out a first group of 14 items. A first statistical approach was to compare the new scale with the well-known Hamilton anxiety scale by the way of a sample of 81 ratings. After a first factor analysis, a sub-group of 12 items were definitely retained. These items were split in 4 factors which permitted to present the factorial results in diagram [Acta psychiat. belg., 87, 704-713 (1987)].
Adult↗
[Data of broncho-alveolar lavage and pulmonary histiocytosis X].
The data obtained from broncho-alveolar lavage in 12 cases of pulmonary histiocytosis X explored between 1978 and 1986 are reported. The usefulness of this simple and reliable examination to the diagnosis and follow-up is emphasized. The diagnosis, suggested by radiography of the chest, may be suspected on cytological findings of hypercellularity, macrophage alveolitis and eosinophilia. The occurrence of neutrophilic hypergranulocytosis indicates an unfavourable course towards fibrosis. An increase of cells marked with monoclonal OKT6 antibodies (70% of the cases in this series) contributes to the diagnosis of histiocytosis X and is a good indicator of granuloma activity during the follow-up period. Electron microscopy of the alveolar fluid often confirms the diagnosis by showing the specific organelle: the X granule (60% of the cases in this series), thus avoiding exploratory thoracotomy in many patients.
Adolescent↗
[Simultaneous or successive primary multifocal bronchial cancer. Apropos of 12 cases].
Twelve cases of bifocal and bilateral bronchial carcinoma are presented. The two tumours developed successively in 6 cases and simultaneously in 6 cases. Patients' mean age (60 years) was the same as in other lung cancers. Four out of 12 patients produced a history of old ENT or skin cancer. In 11 out of 12 cases the second tumour, undetectable by radiology, was discovered at bronchoscopy. In 2 patients the two tumours had a different histology: adenocarcinoma and squamous cell tumour. In all other cases, both tumours were of the squamous cell type. Treatment of the second contralateral tumour was difficult to determine, especially when the first tumour had been widely excised. However, radiotherapy focused on small endobronchial tumours seemed to give interesting results.
Adenocarcinoma↗
The ability of PK 8165, a quinoline derivative, to reduce responses to a stressful situation in a double-blind study in man.
A double-blind and cross-over study was carried out in order to explore the effects of PK 8165 (a quinoline derivative) on the heart rate, respiratory rate and motor reflex responses produced by an experimental model of stress in 8 healthy volunteers. The stress was induced by repetitive sequences of anticipation of pain (stressful stimulus: S) spaced by resting periods (R). In a control session, the cumulative effects of S resulted, in all subjects, in a progressive increase in heart and respiratory rates; 5 subjects showed a cumulative facilitation in the H reflex (motor reflex response) while the 3 others exhibited a cumulative depression in this motor parameter as a function of repetition of S during the session. The three doses (50, 100, 150 mg) of PK 8165 produced a very significant dose-dependent reduction in these responses during both stressful periods and resting sequences. Furthermore, the baseline values of respiratory and especially heart rate were also significantly reduced in a dose-dependent fashion by PK 8165. In contrast, the treatment with placebo did not significantly modify these parameters, compared to control values. The functional implications of these data are discussed in terms of stress-induced activation of some CNS structures and of the possible mechanisms of the "anti-stress" effect of PK 8165.
Adult↗
Evaluation of the sedative properties of PK 8165 (pipequaline), a benzodiazepine partial agonist, in normal subjects.
The sedative properties of two doses (50 and 150 mg) of a benzodiazepine partial agonist, PK 8165 (pipequaline), were compared to diazepam 10 mg and placebo in 12 normal volunteers. The assessment, performed before drug intake and 2 and 5 hours after drug intake, included a battery of visual analogue scales and standardized computerized tests (labyrinths, series of digits, colour test, and Zazzo test). Results showed that, at low dose, PK 8165 is not only devoid of any sedative effect but presents psychostimulating properties. In contrast, diazepam 2 hours after intake and PK 8165 150 mg, 5 hours after drug intake induced a significant decrease in performance compared to placebo. This study suggests that small doses of PK 8165 merits further development as an anxiolytic/psychostimulating drug devoid of sedative properties.
Adult↗
[Poisoning by alcohol, narcotics and psychotropic drugs. A study of alcohol-drug associations in forensic medical thanatological practice].
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Adolescent↗