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Biomedical subjects

A Hirsch

Publications and source records attributed to A Hirsch.

At least 127 records · Page 7Linked to original sources

Isolation, characterization and sequencing of the chicken apolipoprotein-AI-encoding gene.

The chicken ApoAI gene has been isolated and characterized. This gene contains three introns: the first is situated after nucleotide (nt) 41 in the 5'-untranslated region of the gene, the second interrupts the codon specifying the Gly-10 of the prepeptide, and the third disrupts the codon for Asp42 in the mature ApoAI protein. The chicken ApoAI gene has 62.6% sequence similarity with the human and 65.0% similarity with the rat gene. Intron-exon organization of the chicken gene is similar to that of human and rat ApoAI genes. Two different transcriptional start points (tsp), only 2 nt apart from each other, have been obtained for the chicken ApoAI gene. The 5'-flanking sequence of the gene contains TAAATA (TATA-like box) and CCACAT (CCAAT-like box) sequences, which are located 21 bp and 96 bp upstream from the tsp, respectively. This gene's sequence and structural organization provide a basis for future studies of the regulation of chicken ApoAI gene expression.

Amino Acid Sequence↗

Effects of endothelin-1 in the isolated heart in ischemia/reperfusion and hypoxia/reoxygenation injury.

The effects of the vasoconstrictor peptide endothelin-1 were examined in the isolated heart during hypoxia, reoxygenation and reperfusion. Isovolumic rat hearts were perfused with Krebs-Henseleit buffer at constant pressure. Cumulative dose-response curves were obtained for endothelin-1 boluses of 0.04 to 400 pmol in five groups of hearts. Coronary flow declined with increasing dosages and was almost abolished at 400 pmol in control hearts. In hearts subjected to mild hypoxia (perfusate PO2 approximately 150 mmHg), the constrictor effect of endothelin-1 was attenuated at moderate dose compared to control hearts (4 vs. 16% flow reduction at 40 pmol; P less than 0.05). The constrictor effect was unaltered in hearts subjected to either 60 min of severe hypoxia (PO2 approximately 35 mmHg) followed by reoxygenation or to 10 min of total ischemia followed by reperfusion (stunning). When hearts were reperfused following 30 min of total ischemia (irreversible injury), the constrictor response to endothelin-1 was potentiated compared to control (e.g. 36 vs. 16% flow reduction at 40 pmol; P less than 0.05). We conclude that endothelin-1 is a potent coronary constrictor in hypoxic, reoxygenated and reperfused heart. The constrictor effect is attenuated during hypoxia, most likely due to the presence of counteracting vasodilator metabolites. During reperfusion, the constrictor effect is unchanged in stunned myocardium, but is augmented in irreversibly injured heart, due to either increased endothelin-1 binding sites or loss of counteracting vasodilator mechanisms such as prostaglandins and/or endothelium-derived relaxing factor.

Animals↗

Behavioural tests: applications and limitations in comparison with brainstem response audiometry.

Conditioned behavioural hearing tests cannot be performed in children before the developmental age of 8 months. Informal tests cannot be used as threshold tests as the stimuli are unspecific in frequency, and the observed reactions are not equivalent to the threshold level. Brainstem response audiometry (BRA) was performed on 47 children (23 normal children and 24 children with mental retardation with or without behavioural disturbances) in whom informal test results were unclear. The BRA was followed up by behavioural tests 1 to 10 years later. In none of the cases did the BRA thresholds indicate better hearing function than the actual threshold noted later on at behavioural tests. High BRA thresholds (up to 75 dB nHL) were found in 5 normal-hearing children with serous otitis media at the time of BRA recording.

Age Factors↗

[Granulo-monocyte growth factors. Their value in pneumonologic oncologic practice].

Granulo-monocytic growth factors are important members of the family of growth factors which alter the biological response. These factors are glycoproteins and are hormones regulating the production of haematopoietic cells and show their adaptation to possible needs. There are four which are currently well recognised; they are now grouped collectively under the term colony-stimulating factor and of these two, GM-CSF and G-CSF are available thanks to genetic engineering and have reached the stage of therapeutic trials. It is essentially the treatment of solid tumours which should lead to the most profound changes in the current management of cytotoxic drugs because they may allow an increase of the dose and a shortening of the duration of the phase of neutropenia and thus the infection risk. In therapeutic pneumonology they would be able to be used as an adjuvant to chemotherapy in small cell cancers and available in protocols using polychemotherapy with a risk of marrow suppression, indeed even permitting the practice of intensified chemotherapy regimes with or without the support of bone marrow graft. However the clinical experience acquired using growth factors remains limited and is almost exclusively restricted to the haematological domain. Although the secondary effects appear tolerable their harmlessness--and notably the absence of a stimulating effect on tumour growth--remains to be shown before extension of their use will lead to any changes of therapeutic strategies.

Antineoplastic Agents↗

[Detection of bronchial cancer. Realities and perspectives].

Primary bronchial cancer is responsible for at least 20,000 deaths per year in France. The treatment of cancer in the clinical phase remains disappointing. Numerous trials, which are reviewed here chronologically, have looked for a way to improve the prognosis by an earlier detection of this tumour. Unfortunately numerous methodological approaches have not been able to avoid the fact that the real value of such an early diagnosis is not always known. The only clear conclusion of these studies is that cytological examination of the expectorate does not lead to an improved survival in patients when compared to that which is obtained with the single radiographic film. However, taking account of the natural history of the disease, it is probably necessary to abandon the concept of an early diagnosis of a tumour which is already too late; it is towards a search for pre-cancerous lesions which are still reversible that the research effort should be turned.

Bias↗

Left ventricular hypertrophy reversal with labetalol and propranolol: a prospective randomized, double-blind study.

Hypertensive patients with left ventricular hypertrophy (LVH) have increased cardiovascular morbidity and mortality. Experimental studies indicate the importance of both the alpha and beta components of the adrenergic nervous system in the development and reversal of LVH. Therefore labetalol (L), a combined alpha and beta blocker, and propranolol (P), a nonselective beta blocker, were evaluated in a randomized, double-blind study of 35 hypertensive patients with echocardiographic evidence of LVH. Following 2 weeks of placebo, L or P was titrated as needed and tolerated to maximum total daily doses of 1600 mg and 640 mg, respectively. A thiazide diuretic was added if necessary for blood pressure control. M-mode echocardiograms were performed at baseline and after 1, 3, 6, and 12 months of blood pressure control. The echocardiograms were read independently by two blinded observers for end-diastolic dimension and wall thicknesses, and left ventricular mass. Fractional shortening, cardiac output, and peripheral vascular resistance were derived using standard formulas. Both drugs reduced blood pressure significantly and comparably. Significant changes in the echocardiographic measurements were observed as early as 1 month and usually persisted throughout the study. Both drugs decreased posterior wall thickness; however, only the decrease in propranolol group achieved statistical significance. Septal wall thickness was reduced by L at 3 and 12 months. End-diastolic dimension increased significantly in the L-treated group at 3, 6, and 12 months of therapy, whereas P had no effect on this measurement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of endothelin-1 in the isolated heart under ischemic and cardioplegic conditions.

We examined the effects of the vasoconstrictor peptide endothelin-1 in isolated hearts under ischemic and cardioplegic conditions. Isolated isovolumic rat hearts were perfused with Krebs-Henseleit buffer at constant pressure. Cumulative dose-response curves were obtained for endothelin-1 boluses of 0.04-400 pmol in four groups of hearts. Coronary flow decreased with increasing dosages and was almost abolished at 400 pmol in control hearts perfused at a constant pressure of 100 mm Hg. In hearts made ischemic by reducing coronary perfusion pressure to 35 mm Hg, thus reducing coronary flow by 76%, the constrictor effect of endothelin-1 was well preserved. The endothelin-1 dose-response curve was unaltered when hearts were perfused with buffer containing 30 mM KCl to abolish mechanical activity without reducing extracellular Ca2+ concentration. A fourth group of hearts was perfused with Ca2(+)-free buffer, thus eliminating the source of extracellular Ca2+ as well as mechanical activity. In this group, the constrictor response to endothelin-1 was largely, but not completely, abolished, with a maximal constrictor effect of only 19% as opposed to 87% in control hearts. We conclude that in isolated rat heart endothelin-1 is a potent coronary constrictor under ischemic perfusion conditions and that absence of mechanical activity does not affect the action of endothelin-1, for which the presence of extracellular Ca2+ is essential. The small residual constrictor response with Ca2(+)-free perfusion is probably due to release of Ca2+ from intracellular stores.

Animals↗

[Cost effectiveness of inpatient hospital care, day hospital care and outpatient consultation in pneumology. Apropos of 162 patients].

The authors report the results of a non-randomised study comparing the efficacy (in terms of confirmation of the diagnosis, the extent of disease, and measurements of airflow obstruction, and of the therapeutic index), and the efficiency in 58 patients suffering from lung cancer as well as 62 patients suffering from chronic airflow obstruction, and 42 asthmatics. These patients were seen in one of three possible services of a respiratory medicine department of a university hospital. The possibilities were inpatient stay in hospital, day hospital, or outpatient consultation. All the patients except one were totally independent, and could be taken into anyone of the three hospital services. The diagnostic efficacy for lung cancer was independent of the type of service used. The day hospital was four times more efficient than inpatient care for lung cancer, and consultation was 3.5 and 4.6 times more efficient than the day hospital for asthma and chronic airflow obstruction respectively. The balance of efficiency and the index of satisfaction experienced by the patients on the service used accentuated these differences.

Ambulatory Care↗

Opportunistic agents in bronchoalveolar lavage in 99 HIV seropositive patients.

During a ten month period, 117 fibreoptic bronchoscopies and bronchoalveolar lavages (BAL) were performed in human immunodeficiency virus (HIV) infected patients suspected of having opportunistic pulmonary infections. The BAL were classified into 3 groups, according to clinical manifestations related to HIV infection at the time of fibreoptic bronchoscopy: pre-acquired immunodeficiency syndrome (AIDS) (n = 54), AIDS with Kaposi's sarcoma (n = 37), AIDS without Kaposi's sarcoma (n = 26). On chest X-ray, diffuse infiltrates were most common (54%), followed by normal X-rays (24%) and localized infiltrates (18%). Amongst the 117 BAL, 68 (58%) yielded at least one opportunistic agent. In 28 BAL performed for pulmonary signs or unexplained fever with normal chest X-rays, one or several opportunistic agents were isolated in 17 samples of BAL fluid. The most frequently identified opportunistic agents were Pneumocystis carinii (in 38% of BAL) and cytomegalovirus (35%); these were associated in 17% of BAL. There was no statistically significant difference in opportunistic agents among the 3 groups of BAL (pre-AIDS, AIDS with Kaposi's sarcoma, AIDS without Kaposi's sarcoma). In particular, cytomegalovirus was found in BAL with the same frequency in these 3 groups.

Acquired Immunodeficiency Syndrome↗

[Methods of stopping smoking].

The majority of smokers who stop smoking do it alone. The methods of stopping are aimed at helping those who cannot achieve this. The different methods used include psycho-therapy (individual-group), medication, and in the first place is nicotine chewing-gum (but also clonidine which opens a new perspective), aversive behaviour and reinforcement methods, hypnosis and acupuncture. The inadequacy of validated controlled trials by biological measurements makes it difficult to compare different methods. The levels of cessation evaluated varies as a function of recruitment, the relationship between the patient and the therapist, and between the association of the different methods. An important factor in the success resides in the motivation of the subjects explaining that the bias of recruitment readily lead to differences in the results which are superior to the action of the therapy itself. Associated to psychotherapy is the use of nicotine chewing-gum in pharmacologically dependent smokers, and seems to give good enough results. Behavioural methods have an important early success level but these are somewhat deceiving in the long-term and are not totally without risk. Acupuncture, hypnosis and the progressive reduction in nicotine levels (nicotine fading) requires controlled studies to judge their own efficacy. The frequency of failure in the first year remains the major current problem in the methods of stopping. It is convenient not only to develop maintenance strategies but also at the sociological level to diminish the environmental pressures inciting people to smoke.

Acupuncture Therapy↗

Measurement of bacterial and fungal air counts in two bone marrow transplant units.

We evaluated air contamination with bacteria and fungi in a transplantation unit, successively housed in two buildings. Bacterial air contamination was least in laminar air flow rooms, and reduced in ultraclean air rooms in comparison with conventional rooms. Similar results were obtained with culture of air for fungi.

Air Microbiology↗

[Passive smoking and respiratory diseases. Current data].

Smoking is now unanimously recognised as a pathological factor and a major carcinogen. It is estimated that it is responsible for around 10% of the overall mortality in France or more than 50,000 deaths per year and in the United States for around 15% of the overall mortality or 300,000 deaths per year. There has been recent evidence that the risk linked to the inhalation of tobacco smoke does not appear only in active smokers, but also in all subjects who are involuntarily exposed to tobacco smoke. We have here planned a general review of the epidemiological studies which have looked for an association between passive exposure to tobacco and respiratory disease. In children, an increase in symptoms and respiratory infections has been observed, as well as a slowing down in pulmonary growth. In adults the effect of involuntary exposure to tobacco smoke seems above all to be carcinogenic. It is estimated that there is a 25% increase in the risk of bronchial cancer in a non smoker married to a smoker when compared to the risk observed in a non exposed non smoker. Thus the disastrous effect of smoking appears without any threshold.

Adult↗

[Comparative study of 2 classical technics of coloration and an indirect immunofluorescent assay applied to research on Pneumocystis carinii in the bronchoalveolar lavage fluid and induced sputum in HIV+ patients].

Two histochemical staining methods, eosine-methylene blue fast (RAL 555) and silver methenamine (modified Grocott's technique), and indirect immunofluorescence assay with an anticyst monoclonal antibody were used to detect Pneumocystis carinii in the broncho-alveolar lavage fluid and induced sputum from 58 HIV+ patients. Immunofluorescence disclosed the largest number of carriers (35 p. cent of examined patients). However, the histochemical staining techniques remain of interest and are the initial method of choice. They are inexpansive and rapid to achieve; less sensitive than immunofluorescence, positive results argue a high enough level of parasitism which leads to clinical manifestations. The increased sensitivity of immunofluorescence has considerably improved the ability to detect Pneumocystis in induced sputum. It allowed us to disclose 18 out 20 carriers (90 p. cent). However when a Pneumocystis is suspected, it is preferable to sample bronchoalveolar lavage fluid. Its examination is quick, easy and quantitative appreciation of results bring important diagnostic arguments. Other parasites, such as toxoplasmas, may also be detected. On the other hand, the examination of expectoration is time consuming and difficult to read and interpret. Therefore, sputum induction for the diagnosis of Pneumocystosis should be reserved to unequiped centers or insufficiently equiped centers (i.e., devoid of intensive care units).

Acquired Immunodeficiency Syndrome↗