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Biomedical subjects

A Leon

Publications and source records attributed to A Leon.

At least 217 records · Page 12Linked to original sources
PubMed1975

The effects of cosmic particle radiation on pocket mice aboard Apollo XVII: IX Results of examination of the nasal mucosa.

The olfactory epithelium, but not the nasal respiratory epithelium, of the four pocket mice (Perognathus longimembris) that survived their flight on Apollo XVII showed both diffuse alterations and numerous disseminated focal lesions. The olfactory mucosa of the mouse that died during flight was also affected, but to a minor degree insofar as could be determined. All this was in contrast to the normal appearance of the olfactory mucosa of the numerous control animals. A number of possible causes were considered: systemic or regional infection; inhaled particulate material (seed dust); by-products from the KO2 bed in aerosol or particulate form; gas contaminants originating in the flight package; volatile substances from the dead mouse; weightlessness; and cosmic ray particle radiation. Where feasible, studies were conducted in an effort to rule in or rule out some of these potentially causative factors. No definitive conclusions were reached as to the cause of the lesions in the flight mice.

Aerosols↗
PubMedDate not supplied

Diclofenac, paracetamol, and vidarabine removal during plasma exchange in polyarteritis nodosa patients.

Since plasma exchange (PE) represents a major treatment for patients suffering from systemic diseases, its influence on the kinetics of three drugs was investigated: vidarabine, used in patients with polyarteritis nodosa associated with hepatitis B virus (eight subjects), and diclofenac and paracetamol for investigative purposes (five subjects). This study confirmed that vidarabine is so rapidly deaminated to form hypoxanthine arabinoside (Hx-Ara) that no detectable concentrations were measured. Hx-Ara levels were used to evaluate vidarabine kinetics; 19.5 +/- 14.6 mg of Hx-Ara were removed by one PE during the first week of treatment (15 mg kg-1 d-1, continuous infusion) and 7.8 +/- 10.2 mg were eliminated by one PE during the second week of treatment (7.5 mg kg-1 d-1, continuous infusion). Based on the vidarabine intake per hour and the resulting quantity of Hx-Ara removed per hour, PE recovery was quite important (ca. 30 per cent), during both the first and second weeks of continuous infusion. Data were subject to large interindividual variability. However, these results do not favor vidarabine dosage supplementation in this indication because the duration of PE is less than 8 per cent of a daily administration period. For paracetamol (1 g, single oral dose) and diclofenac (100 mg, single oral dose), the fractions of drug removed during PE effected within 2 h of drug intake, were respectively 5.0 +/- 3.1 per cent and 13.6 +/- 9.5 per cent, while plasmapheretic clearance reached, respectively, 13.0 +/- 10.7 per cent of the systemic clearance for paracetamol and 23.0 +/- 1.0 per cent for diclofenac.

Acetaminophen↗
PubMedDate not supplied

Purification and characterization of Fab fragments from anti-mouse NGF polyclonal antibodies.

A functional role for Nerve Growth Factor (NGF) in the peripheral nervous system is well-documented, but a similar case for NGF in the central nervous system remains to be established. One approach to answering this question would be the availability of high-affinity monospecific Fab fragments obtained against NGF. In the present studies we describe the preparation and characterization of such Fab fragments from anti-mouse NGF polyclonal antibodies. Following their purification by the use of a NGF Sepharose-coupled affinity column, the Fab fragments were examined for biological competence in several ways. In vitro, the anti-Fab fragments blocked the neuronotrophic activity of NGF, as measured by the survival of chicken embryonic day 8 dorsal root ganglion neurons. In vivo, these Fab fragments, when administered systemically to neonatal rats, produced a decrease of noradrenaline levels in two sympathetically innervated organs, the heart and the spleen. These findings suggest that affinity purified Fab fragments of anti-NGF antibodies can be a useful tool for studying the physiological function of NGF in the nervous system.

Animals↗
PubMedDate not supplied

Exogenously administered gangliosides fail to increase in vivo metastatic frequency or in vitro growth of murine neoplastic cells.

The influence of gangliosides on tumor growth and frequency of metastasis in vivo, as well as growth of neoplastic cells in vitro, was tested utilizing the mouse fibrosarcoma cell line MN4. In mice receiving intramuscular tumor transplants, injections of a ganglioside mixture twice daily did not influence the tumor volume or the number of spontaneous metastases per animal. Furthermore, in mice receiving the cells by tail vein injection, injections of a ganglioside mixture once or twice daily did not affect the number of metastatic foci in the lungs. Preincubation of neoplastic cells with the ganglioside mixture decreased the number of metastatic foci in the lungs of mice receiving the cells by tail i.v. injection. The addition of ganglioside mixture to the culture medium for up to a 48-h incubation period had no effect, independently of the cell density utilized, on either the rate of DNA synthesis or the relative numbers of neoplastic cells as compared to controls; at higher ganglioside concentrations, growth was actually reduced. These results are interpreted to indicate that gangliosides, under the present conditions, do not influence tumor growth and metastatic neoplastic capacity in vivo, and growth in vitro.

Animals↗
PubMedDate not supplied

Secular trends in lifetime onset of MDD stratified by selected sociodemographic risk factors.

We used multivariate proportional hazards (Cox) models to investigate the effects of cohort of birth on age of first onset of major depression measured independently at two occasions, about six years apart, in the first degree relatives of probands with major affective illnesses. We estimated the cohort trends in strata defined by sociodemographic and other measures, to see if the cohort trends are the same across strata. Graphical summaries of the trends reveal a generally consistent pattern of increasing rates and earlier age of onset with successive birth cohorts, across all strata examined. The relatives with a divorced parent had a somewhat delayed secular increase, suggesting either a ceiling effect or an interaction of the two risk factors (recent cohort of birth and divorced parents) such that the combined effect is less than the sum of the individual effects. Otherwise, the cohort effect is persistent and ubiquitous in this sample.

Adult↗
PubMedDate not supplied

Persistence of depressive symptoms and cardiovascular death among patients with affective disorder.

OBJECTIVE: Studies of both community and clinical samples have associated depressive symptoms with risks for subsequent cardiovascular morbidity and mortality. Because the physiological mechanisms thought to underlie this link would be cumulative in their effects, the following analyses tested the prediction that risks for cardiovascular death would increase in proportion to the persistence of depressive symptoms in a long-term follow-up. METHODS: Baseline assessment was performed as patients sought treatment for major depressive disorder, mania, or schizo-affective disorder. Follow-up evaluations occurred semiannually for the next 5 years and annually thereafter. The 903 patients described, observed for a mean of 11.0 years (SD = 5.2 years), were divided into thirds according to the proportion of follow-up weeks in episodes of major depressive disorder, schizoaffective disorder, or intermittent depressive disorder. The resulting groups were then compared by cumulative risks of cardiovascular death. RESULTS: Patients whose depressive symptoms were the most persistent were no more likely to die of cardiovascular causes than were those with the fewest weeks ill. A regression analysis showed that older age and the presence of cardiovascular disease at baseline, but not the subsequent chronicity of depressive symptoms, predicted cardiovascular death. CONCLUSIONS: The physiological concomitants of depressive illness apparently do not promote cardiovascular mortality in a cumulative manner. Efforts should be directed toward identification of risk factors common to both lifetime depressive symptoms and cardiovascular morbidity.

Adult↗
PubMedDate not supplied

Comparison between two methods in the determination of circulating chromogranin A in neuroendocrine tumors (NETs): results of a prospective multicenter observational study.

Several methods for analyzing CgA using either monoclonal or polyclonal antibodies have been developed, which differ in their diagnostic performance. The present paper describes the results of a prospective multicenter study aimed at comparing the clinical value of the two most widely used commercially available CgA assay kits in patients affected by neuroendocrine tumors (NETs). Two hundred sixty-one patients from 40 different centers and 99 healthy subjects were evaluated. CgA levels were measured with two different methods, a two-step immunoradiometric assay (IRMA) and an enzyme-linked immunosorbent assay (ELISA). CgA was measured centrally by two reference laboratories, one of which used IRMA and the other ELISA, and it was measured by the participating institutions with the method routinely used by each of them. The major findings of the present study were: (i) the two assays for the determination of CgA present good diagnostic performance; (ii) both assays are robust and guarantee comparable results when applied in different settings (central vs local laboratory); (iii) the negative/positive cutoff points (87 ng/mL for IRMA and 21.3 U/L for ELISA) were established according to standardized criteria; (iv) the results obtained with the two assays in basal clinical samples of patients affected by NETs show an apparently satisfactory correlation (rs = 0.843, p < 0.0001). However, a possibly clinically meaningful 36% discordance rate was found. These findings support the hypothesis that the two CgA kits might provide partially different information.

Adult↗
PubMedDate not supplied

Third-generation PSA: ultrasensitive or ultraprecise assay?

The ultrasensitive PSA assay has been recently acknowledged as a useful tool for the monitoring of patients prostatectomized for prostatic cancer. We have evaluated a commercially available ultrasensitive PSA assay (Immulite Third Generation PSA-DPC-Los Angeles CA) in comparison with the routinely used PSA (Immulite PSA-DPC-Los Angeles CA). When evaluated with different approaches, the analytical sensitivity of ultrasensitive PSA ranged between 0.0029 and 0.0038 ng/ml. The biological detection limit was 0.0098 ng/ml. Dilution of samples with low PSA levels showed a good recovery (from 88 to 113%) up to 1:128 dilution factor (final PSA levels ranging from 0.004 to 0.016 ng/ml in different samples). The assay precision was excellent in the low dose range, the highest interassay interadjustment CV among replicates being 5.84% when assaying serum samples with PSA lower than 1.0 ng/ml. Besides its role in the follow-up of prostatectomized patients, the evaluated ultrasensitive PSA could be reliably used for the detection of clinically meaningful PSA variations in the low dose range, and it could therefore be a candidate for the assessment of PSA velocity.

Aged↗
PubMedDate not supplied

[Interferon-beta response in multiple sclerosis associated with pre-treatment disability].

AIM: To study pre-treatment clinical features and influence of neutralising antibodies (NABs) in clinical response to interferon-beta (IFNB). PATIENTS AND METHODS: We analysed clinical characteristics and NABs to IFNB in 96 multiple sclerosis patients treated with IFNB. Clinical response was established by clinical criteria: = 1 relapse or an increase = 0.5 or 1 point in the Expanded Disability Status Scale (EDSS) score after one year of treatment compared with the year prior to IFNB therapy. RESULTS: Baseline clinical characteristics were similar for responders and non-responders, except for a significantly higher baseline mean EDSS score in non-responders. Time-to-first-relapse was longer and the number of patients relapse-free was higher for NAB-negative patients, but we were unable to show an association with the disability status, probably due to sample size. CONCLUSIONS: Response to IFNB was significantly associated with pre-treatment disability measured by the EDSS. The presence of NABs to IFNB presented a delayed negative effect for relapses.

Adolescent↗
PubMedDate not supplied

[Extraction of drugs in plasma exchange].

Plasma exchange has been proposed for treating diseases mediated by circulating immune complexes. Removal of drugs during plasma exchange is a complex function of pharmacokinetic characteristics and specifications of the plasma exchange procedure: the time of plasma exchange, the filtered volume of plasma, the number of procedure. The effect of plasma exchange on the kinetics of drugs can be evaluated by different parameters: amount eliminated, extracorporeal clearance, fractional drug removal, extracorporeal elimination rate constant. Knowledge of the impact of plasma on the elimination of drugs is essential to the design of the dosage regimen in patients treated with plasma exchange. The fraction of the estimated amount in body removed by plasma exchange is the best parameter to evaluate the effectiveness of the exchange procedure, but it is necessary to know the proportion of body pool of drug at the start of the plasma exchange. Drug recovery by each exchange may account for 0.5%-30% of the dose. Controlled studies are needed to quantify the effects of plasma exchange on drug therapy. Dosage adjustment is sometimes required.

Humans↗