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Biomedical subjects

H Schaefer

Publications and source records attributed to H Schaefer.

At least 55 records · Page 3Linked to original sources

[Bone marrow culture, cytochemistry and electron microscopy in agar in patients with preleukemic syndrome and aplastic anemia].

Thirty-seven patients with chronic cytopenia were studied using a CFU-c assay in agar. On the basis of the growth pattern three types of preleukaemic syndrome (PL) and two types of aplastic anaemia were distinguished. Further evaluation of the bone marrow dysfunction was attempted with a combined application of cytochemistry and electron microscopy for the morphologic study of cells proliferating in vitro. Well-defined maturation defects in the growing cells from the bone marrow of patients with PL were demonstrated with cytochemical stainings performed in agar. These results were supported by electron microscopic findings of Auer-body-like inclusions in "statu nascendi" in the vacuoles of preleukaemic cells. On the basis of our results a high risk group of PL for development of overt leukaemia and a group of patients with a grave prognosis in aplastic anaemia were distinguished. The data obtained are relevant for the clinical diagnosis and prognosis of patients with cytopenias.

Adult

Microcalorimetric investigations of the metabolism of isolated human epidermis.

Microcalorimetry was used for the evaluation of metabolic and enzyme activity in human epidermis. The endogenous metabolism with a heat production Q = -2 muW/mg wet weight could be stimulated to Q = -12 muW/mg by adding glucose to the buffer. To test the enzyme activity, hydrogenation of pyruvate to lactate by lactate dehydrogenase (LDH) was chosen as an essential step of anaerobic glycolysis. The LDH activity of epidermis slices amounted to 22 mU/mg epidermis. The microcalorimetric method is discussed as a test procedure for specimens of healthy and diseased skin and for cell cultures.

Calorimetry

The quantitative distribution of percutaneously applied caffeine in the human skin.

The distribution coefficient of caffeine (water/n-Octanol) and the estimation of caffeine in urine after local application indicate to a high permeation rate of caffeine through the skin. This could be confirmed by using different vehicles in vivo and in vitro. 14C labeled caffeine penetrates rapidly the epidermis and corium. The maximum of absorption is reached at 100 min after local application in vivo. In vitro by absence of the transport possibilities of blood and lymph vessels, the concentration at 1,000 min after local application is 450 X higher than in vivo. Therefore, after 1,000 min in vivo the concentration of caffeine in the different skin layers is very low.

Administration, Topical

Contraception via topical application? - A review.

The skin, generally speaking, is not an absorption organ but one of its major functions is the protection of the body against the entrance of foreign material. Under certain circumstances, however, drugs can be introduced into the skin and thereby into the body as can be seen in the topical treatment of skin diseases. Though percutaneous pharmacokinetics of steroids seem appropriate for contraception, the variability of the absorption process appears to be too high for this purpose.

Absorption

Reversible binding of 5- and 8-methoxypsoralen to human serum proteins (albumin) and to epidermis in vitro.

Binding of the two photosensitizers, 8-methoxypsoralen (8-MOP) and 5-methoxypsoralen (5-MOP), to serum proteins and to epidermis was measured. 8-MOP binds to serum proteins with an apparent dissociation constant (Kd) of 4 x 10(-5) M. Under conditions of oral therapy, serum concentrations of the photosensitizer 2 h after administration are usually in the range of 100-1000 ng per ml serum. In this concentration range, 75-80% of the drug was found to be reversibly bound to serum proteins. 5-MOP shows a higher binding affinity to serum proteins and 98-99% of the drug is protein bound. The binding of both psoralen derivatives appears to take place mainly to serum albumin. 5-MOP and 8-MOP bind to different and non-interacting sites on serum proteins and the binding of the one has no effect on the binding of the other methoxypsoralen. Both photosensitizers bind reversibly to human epidermis. 8-MOP concentration in the epidermis is increased by ten to twenty fold compared with the equilibrium buffer. 5-MOP shows a higher binding affinity, resulting in a higher tissue concentration of the photosensitizer. As in serum, the two drugs appear to be bound in the epidermis to independent and non-interacting sites. No binding competition was found between the two methoxypsoralens and hydrocortisone, fluocinonide and acetyl salicylic acid, either in serum or in epidermis, using up to 1000 fold higher concentrations as compared with those of 5-MOP and 8-MOP.

Binding, Competitive

[Smoking as a psychological and social problem].

1. The ill-effects of smoking on health not only concern the smoker but the entire population living in the same society and sharing the economy. Smoking is associated with a general increase of costs involved with increased morbidity, lowering of the social product and excess mortality. 2. The main prolem in weaning from smoking is related to the origin of smoking which is in large measure unknown. Smoking habits should not be analyzed on an individual basis only. It represents a "minor addiction" with the origin within the society. This is the result of an analysis of motives leading to smoking. Social habits, examples, deprivation of senses, dullness, anxiety, stress, and smoking as a symbol of status play a major role. 3. Stress carries a dual risk, it encourages to smoking and it exerts direct effects an organ function. 4. Smoking is enhanced by its somatic effects which activate in turn again smoking. Weaning from smoking does not affect the origin of the addiction thereby remaining symptomatic treatment. 5. There is a constant replacement of old smokers with smokers originating in the young generation. Smoking habits have the tendency to spread out of the smoking population over the non-smokers. A combat against this infiltration can only be successful by creating new values and by producing a new habit of non-smoking.

Health Expenditures

8-Methoxypsoralen (8-MOP) in human skin: penetration kinetics.

Penetration kinetics of 8-methoxypsoralen (8-MOP) into human skin have been investigated under in vitro conditions. The dependence of the resulting tissue concentration on time of penetration, drug concentration in the applied preparation and vehicle composition has been studied. Tissue concentration of the drug was found to increase with time of penetration; however, in both horny layer and epidermis, this increase was followed by a significant decrease in concentration, (after 100 to 300 min), although a large amount of unpenetrated drug was present on the horny layer surface at all times. In contrast to this, 8-MOP accumulated in the lower corium and subcutis and reached concentrations higher then those found in the upper corium and epidermis. This accumulation of the drug is a consequence of the in vitro conditions and its amount is proportional to that amount that under in vivo conditions would have been taken up by the capillary system. Penetration was dependent on vehicle characteristics and was found to increase with increasing polarity of the vehicle. The penetration was found to be directly proportional to the applied concentration; however, the percentage of the drug that actually penetrated was inversely proportional to the applied concentration.

Dose-Response Relationship, Drug

PUVA appraisal.

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Animals

Quantitative determination of percutaneous absorption of radiolabeled drugs in vitro and in vivo by human skin.

We have measured concentrations of about 30 drugs in the living layers of the skin under conditions which provide data which are applicable in therapeutic treatment. Since the skin is a thin organ and small amounts of drug represent high target concentrations, it is necessary to select a sensitive quantitative method; observation of the kinetics of absorption using radiolabeled drugs is the method of choice. Because of possible hazards--and legal and ethical problems--absorption studies in human skin are commonly performed in vitro. Related in vivo investigations demonstrate the relevance and the limitations of the in vitro experiments. The main hindrance against penetration of drugs is by the horny layer. The barrier-function of this layer--if it is undisturbed--may be described by a multilayer model. The reciprocal function, the reservoir function, is important for the efficiency of topical treatment; it also plays a role in determining the unique pharmacokinetics of drug absorption in the skin and percutaneous resorption. If the horny layer is injured, i.e. in diseased skin, both the barrier and the reservoir functions are disturbed. In consequence, drug concentrations in the skin--and percutaneous resorption--may be greatly enhanced, and topically applied drugs may enter preferentially into diseased areas. The form of application, such as ointment, solution, etc. influences the penetration kinetics in such a specific manner that a specific vehicle for a specific drug should always be postulated. The frequently discussed hazards of side effects due to percutaneous resorption of drugs like corticosteroids are a function of the treated area rather than of its penetration capacity. Thus the indication for local or oral treatment of severe dermatoses should be considered in terms of the affected area. The relatively frequent side effects in the skin itself which originate from unnecessarily high drug concentrations and long term treatment must also be taken into account.

Administration, Topical