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Biomedical subjects

M Schadel

Publications and source records attributed to M Schadel.

At least 19 recordsLinked to original sources
PubMed2000

Chemical characterization of bohrium (element 107)

The arrangement of the chemical elements in the periodic table highlights resemblances in chemical properties, which reflect the elements' electronic structure. For the heaviest elements, however, deviations in the periodicity of chemical properties are expected: electrons in orbitals with a high probability density near the nucleus are accelerated by the large nuclear charges to relativistic velocities, which increase their binding energies and cause orbital contraction. This leads to more efficient screening of the nuclear charge and corresponding destabilization of the outer d and f orbitals: it is these changes that can give rise to unexpected chemical properties. The synthesis of increasingly heavy elements, now including that of elements 114, 116 and 118, allows the investigation of this effect, provided sufficiently long-lived isotopes for chemical characterization are available. In the case of elements 104 and 105, for example, relativistic effects interrupt characteristic trends in the chemical properties of the elements constituting the corresponding columns of the periodic table, whereas element 106 behaves in accordance with the expected periodicity. Here we report the chemical separation and characterization of six atoms of element 107 (bohrium, Bh), in the form of its oxychloride. We find that this compound is less volatile than the oxychlorides of the lighter elements of group VII, thus confirming relativistic calculations that predict the behaviour of bohrium, like that of element 106, to coincide with that expected on the basis of its position in the periodic table.

Journal Article↗
PubMed1999

[Referrals to an emergency department--are there differences between self-referrals and referrals from general practitioners?].

The Israeli health system has been undergoing major changes in recent years. Considerations of cost containment have led sick funds to open new out-of-hours services in the community to reduce visits to hospital emergency departments. Referred and self-referred visits to our emergency department during a 1-month period were studied. Patients after trauma or whose visits resulted in hospitalization were excluded. Of the 505 encounters 56.3% were of women; the average age was 52.5 +/- 19.3 years (range 18-96). 57.4% visits were during working hours of primary care clinics ("working hours"), while the others were "out-of-hours" visits. Only 52.7% had a referral letter, 75% of them from the family physician. The quality of the handwriting in 46% was good, in 44% fair and the remaining 10% were illegible. A specific clinical question was asked in only 16% of the letters. A third of "working-hours" visits were self-referrals, rising to 64% in "out-of-hours" visits (p < 0.001). The most common diagnoses in discharge letters were: chest or abdominal pain, asthma, back pain, headache, nephrolithiasis and upper respiratory tract infection. The rate of self-referrals was relatively high throughout the day. Cost-containment efforts did not seem to eliminate self-referrals with "primary care" problems. The quality of referral letters should be improved both with regard to format and content.

Adult↗
PubMed1995

Pharmacokinetics of dextromethorphan and metabolites in humans: influence of the CYP2D6 phenotype and quinidine inhibition.

Dextromethorphan is primarily metabolized to dextrorphan by cytochrome P450 2D6 (CYP2D6), a genetically polymorphic enzyme in humans. Dextrorphan is an active metabolite that produces phencyclidine-like behavioral effects in animals and exhibits anticonvulsant and neuroprotective properties in a variety of experimental models. In these studies, we examined the effects of CYP2D6 phenotype and quinidine inhibition on the pharmacokinetics of dextromethorphan and its metabolites in humans. After a single oral dose of dextromethorphan HBr (30 mg), the major metabolites in the plasma of extensive metabolizers (N = 5) were conjugated dextrorphan and conjugated 3-hydroxymorphinan. Free dextrorphan concentrations were about 100-fold less than the conjugated dextrorphan, and dextromethorphan was not detectable. Pretreatment of these subjects with 100 mg of quinidine, a selective inhibitor of CYP2D6, significantly suppressed the formation of dextrorphan and elevated the concentrations of dextromethorphan (t1/2, 16.4 hours). In poor metabolizers (N = 4) given the same dose, dextromethorphan was the major component in the plasma with a t1/2 of 29.5 hours. Present at concentrations 5- to 10-fold less were conjugated dextrorphan and the other two metabolites. Urinary recovery studies indicated that the inhibition by quinidine was reversible and that the elimination of dextromethorphan primarily depends on CYP2D6 activity rather than renal elimination. These data demonstrated that the CYP2D6 phenotype and the concurrent administration of quinidine significantly affect the disposition of dextromethorphan and the formation of the active metabolite dextrorphan and are important factors to be considered in studies of the pharmacologic and behavioral effects of dextromethorphan.

Adult↗
PubMed1993

CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone.

The contribution of cytochrome P450 2D6 (CYP2D6) to the formation of hydrocodone's active metabolite, hydromorphone, was examined in vitro and in vivo. Human liver microsomes prepared from an individual homozygous for the D6-B mutation of the CYP2D6 gene catalyzed this reaction at a negligible rate. Urinary metabolic ratios of hydrocodone/hydromorphone were highly correlated with O-demethylation ratios for dextromethorphan, an established marker drug of CYP2D6 activity (rs = 0.85; n = 18). The kinetics of hydrocodone after a single oral dose and its partial metabolic clearance to hydromorphone were investigated in five extensive metabolizers of dextromethorphan, six poor metabolizers, and four extensive metabolizers after pretreatment with quinidine, a selective inhibitor of CYP2D6 activity. The mean values for partial metabolic clearance by O-demethylation in the three groups were 28.1 +/- 10.3, 3.4 +/- 2.4, and 5.0 +/- 3.6 ml/hr/kg, respectively. No statistically significant phenotypic differences in physiologic measures were observed. However, over the first hour after dosing, the extensive metabolizers reported more "good opiate effects" and fewer "bad opiate effects" than poor metabolizers and extensive metabolizers in whom CYP2D6 was inhibited by quinidine. These data establish the importance of CYP2D6 in the formation of hydromorphone from hydrocodone and suggest that the activity of this enzyme may limit the abuse liability of hydrocodone.

Cytochrome P-450 CYP2D6↗
PubMed1977

Stroke: incidence and risk factors.

The incidence of stroke was estimated prospectively in a total population of 2,502 persons over age 65 who resided in homes for the aged. The incidence in persons born in Asian and African countries was close to that in persons born in European countries. No sex differential was found in either ethnic group, and there was no significant increase in the incidence of stroke with advancing age in either sex. In the European population, prior heart disease was the strongest risk-increasing factor, ranking ahead of hypertension. Diabetes mellitus was not associated with a higher risk of stroke among the women; the findings for the men were inconclusive. In the Afro-Asian population, the risk of stroke was related to heart disease and diabetes mellitus but was not associated with blood pressure. Total serum cholesterol or relative weight was not associated with stroke in either group. The early establishment of programs for the control of hypertension and stroke appears most desirable.

Age Factors↗
PubMed1976

The initial manifestations of acute myocardinal infarction.

A review of 132 consecutive patients 65 years of age and older who had a myocardial infarction showed that two-thirds of them experienced pain at onset. Pain was the only symptom leading to bedside diagnosis in one-fourth of the patients. Pain at onset combined with sudden or increased dyspnea was present in one-fifth of the patients and pain associated with other symptoms in one-sixth. Dyspnea unaccompanied by pain heralded onset of infarction in one-fifth of the patients, and in almost 7 percent, onset was marked only by other symptoms. Cerebral symptoms dominated onset in one-tenth of the patients. Preexisting coronary heart disease, hypertension, or diabetes was not predictive of painless infarction. To avoid pitfalls and facilitate bedside diagnosis of infarction, physicians should be aware of the different clinical presentations of painless infarction in the aged, which occurred in over one-third of the patients in this cohort. They also should suspect the possibility of myocardial infarction in any patient in whom symptoms are not clear, even when they are mild and unobtrusive. Questioning of the elderly patient, his family, or others around him as early as possible after the onset of an acute attack is likely to elicit a history of pain, which may lead to the correct diagnosis.

Acute Disease↗