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Biomedical subjects

H C Korting

Publications and source records attributed to H C Korting.

At least 145 records · Page 8Linked to original sources

Liposome encapsulation improves efficacy of betamethasone dipropionate in atopic eczema but not in psoriasis vulgaris.

The effect of a liposomal preparation of beta-methasone dipropionate (0.039%, BDP) has been compared to that of a commercial propylene glycol-gel containing 0.064% BDP in a double-blind, randomized, paired trial lasting 14 d in 10 patients with atopic eczema and 10 patients with psoriasis vulgaris. In eczema, the liposome preparation tended to reduce erythema and scaling more than the conventional gel, the difference in the latter parameter being significant on Day 7. There was greater improvement of psoriasis on the side treated with the reference gel. Hence, liposome encapsulation of BDP may increase the antiinflammatory action but not the antiproliferative effect. Since inhibition of mitotic activity is linked to the atrophogenicity of topical corticosteroids, the results suggest that liposome encapsulation may improve the benefit-risk ratio in eczema.

Adult↗

Skin tissue fluid levels of cefotiam in healthy man following oral cefotiam hexetil.

Cefotiam hexetil is a pro-drug of cefotiam available for oral administration. To evaluate cefotiam concentrations at the active site in skin and soft-tissue infections, drug levels in skin suction blister fluid (SBF), cantharides blister fluid (CBF) and serum were determined. Six healthy subjects received oral cefotiam 400 mg as cefotiam hexetil. On an other day 200 mg was injected intravenously. Following the oral dose, the bioavailability of cefotiam was 45.5%, and the maximum concentration in serum of 2.6 mg.l-1 was obtained at 2.1 h. Peak concentrations in both types of blister fluid (0.9 mg.l-1) were significantly lower than after the iv dose (SBF 1.4 mg.l-1, CBF 1.5 mg.l-1), and the peak levels occurred later (3.3 versus 1.5 h in CBF). Despite the delay, the extent of penetration was about 100% following either mode of administration (SBF, iv dose 112%, oral dose 117%). The cefotiam level in skin blister fluids declined significantly more slowly than the serum level. Following the oral dose, the mean terminal half life was serum 0.8 h, SBF 2.6 h and CBF 4.6 h. Cefotiam concentrations in the blister fluids were close to the MIC90 of Staphylococcus aureus, S. epidermis and H. influenzae and exceeded the MIC90 of Streptococci, E. coli and Proteus mirabilis. Thus, the oral administration of cefotiam 400 mg t.i.d. should be curative in the majority of bacterial infections of the skin and soft-tissues.

Administration, Oral↗

Levels of itraconazole in skin blister fluid after a single oral dose and during repetitive administration.

Oral itraconazole is effective in the treatment of mycoses. To measure its concentrations in the tissue, levels of total and non-protein-bound itraconazole were determined in serum, suction-induced blister fluid, and cantharides-induced blister fluid. Six healthy subjects received 200 mg as a single dose, followed by 100 mg/day for 10 days. Itraconazole binding in suction-induced blister fluid (99.54%) and cantharides-induced blister fluid (99.77%) was calculated from plasma protein binding (99.8%). The single-dose study showed the drug levels in blister fluid to increase more slowly than those in serum. The terminal half-life of itraconazole in serum was 22.5 +/- 3.2 hours. Suction- and cantharides-induced blister fluid levels declined in parallel. After the final dose, itraconazole penetration into cantharides-induced blister fluid was only 70%. Moreover, trough levels of unbound itraconazole in suction- and cantharides-induced blister fluid were 0.239 +/- 0.115 and 0.334 +/- 0.101 ng/ml and thus were significantly lower than free itraconazole levels in serum (0.422 +/- 0.125 ng/ml). Thus a distribution equilibrium between serum and blister fluids was not obtained. Free drug concentrations in suction- and cantharides-induced blister fluid were far lower than the minimal inhibitory concentration values for Candida ssp. and dermatophytes.

Administration, Oral↗

Increase of the relative frequency of penicillinase-producing Neisseria gonorrhoeae strains to more than five per cent in Munich.

The relative frequency of penicillinase-producing Neisseria gonorrhoeae strains isolated from Munich STD patients nowadays clearly exceeds five percent. Penicillin resistance is either due to the 3.2 or 4.4 Megadalton plasmid. Similar trends are reported from other European countries. Therefore, treatment with third generation cephalosporins such as ceftriaxone, cefotaxime or others is now generally advisable not only in the Far East and Central Africa but also in Central Europe.

Enoxacin↗

In vitro susceptibility of dermatophytes from Munich to griseofulvin, miconazole and ketoconazole.

Various recent clinical isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis and Epidermophyton floccosum from Munich were subjected to antimicrobial susceptibility testing using the microdilution method. Both azoles miconazole and ketoconazole were found to be more active than griseofulvin. Comparatively high inhibitory concentrations of griseofulvin were especially found with Tr. mentagrophytes. On the whole miconazole turned out to be even somewhat more effective than ketoconazole. Considering the minimum inhibitory concentrations found at least some of the strains tested might not be open to eradication in clinical terms with conventional treatment protocols.

Arthrodermataceae↗

Multiple-dose pharmacokinetics of ofloxacin in serum, saliva, and skin blister fluid of healthy volunteers.

The pharmacokinetics of ofloxacin were determined in six healthy volunteers after oral administration of 200 mg twice daily for 3.5 days. To study the pharmacokinetic behavior at the target site in bacterial infection of the skin, drug concentrations were determined in suction blister fluid (SBF) and cantharides blister fluid (CBF), as well as in serum and saliva. Ofloxacin was measured by a high-performance liquid chromatographic assay. Ofloxacin concentrations in saliva amounted to 61 +/- 3% of levels in serum. After the final dose, ofloxacin concentrations in blister fluid and serum declined in parallel. Terminal half-lives of ofloxacin in blister fluids (SBF, 7.0 h; CBF, 6.3 h) were in accordance with serum half-life (6.6 h). Favorable penetration into the skin is suggested by high area under the concentration-time curve ratios for blister fluid and serum (CBF, 1.1; SBF, 1.3). During repeated ofloxacin intake, drug levels in SBF and CBF at 12 h amounted to 0.94 and 1.10 micrograms/ml. Thus, ofloxacin levels in the skin are well above the MIC for 90% of strains tested for, e.g., Staphylococcus aureus, Staphylococcus epidermidis, Neisseria gonorrhoeae, and various members of the family Enterobacteriaceae. This should also hold true with respect to other tissues.

Adult↗

Experimental evidence for amide hydrolysis of indomethacin in rabbit skin.

Amide hydrolysis of indomethacin was investigated in rabbit skin using the isolated perfused rabbit ear model. Indomethacin was applied topically on the surface area of 4 rabbit ears using a 1% alcoholic solution (Elmetacin). Indomethacin and its hydrolytic product N-deschloro-benzoyl-indomethacin (DBI) were determined in the venous efflux. The concentrations of indomethacin and DBI increased during the first 160 min and remained constant thereafter, the concentrations amounting from 0.041 +/- 0.001 to 0.497 +/- 0.018 nmol/min/cm2 (indomethacin) and from 0.84 +/- 0.03 to 3.24 +/- 0.31 pmol/min/cm2 (DBI). Thus steady state was reached with both substances, indicating a formation of DBI in the range of 0.65-2.01%. Considering the low hydrolytic turnover rate, the limited efficacy of topically applied indomethacin in the treatment of skin diseases does not seem to be due to extensive metabolic inactivation via amide hydrolysis in this target organ.

Amides↗

Dubowitz syndrome: atopic dermatitis, low birth weight dwarfism and facial dysmorphism.

The association of low birth weight dwarfism, distinct facial dysmorphism and eczematous skin lesions has been described repeatedly since the first description by Dubowitz in 1965. The way of inheritance seems to be in some cases autosomal recessive. Because of the rarity of this entity, another case is reported showing an additional preauricular fistula.

Child, Preschool↗

Soluble interleukin-2 receptors in serum and urine of patients with chancroid and their response to therapy.

To investigate cell-mediated immune response in chancroid, soluble interleukin-2 receptor levels in serum and urine samples of healthy individuals and patients were measured by an enzyme-linked immunosorbent assay. Increased levels both in serum and in urine were observed in cases of Haemophilus ducreyi infection. In patients showing a prolonged incubation period, urine levels exceeded serum values. Therapy led to a reduction of elevated interleukin-2 receptor levels in serum and in urine.

Chancroid↗

Differences in the skin surface pH and bacterial microflora due to the long-term application of synthetic detergent preparations of pH 5.5 and pH 7.0. Results of a crossover trial in healthy volunteers.

Skin cleansing preparations consisting of identical synthetic detergents but differing in pH-value (pH 5.5 and 7.0) were applied twice daily on the forehead and forearm of healthy volunteers in a randomized crossover trial. The skin surface pH was found to be significantly higher when the neutral preparation had been used, as was the propionibacterial count (p less than 0.05). The number of propionibacteria was significantly linked to the skin pH. Hence even minor differences in the pH of skin cleansing preparations seem to be of importance for the integrity of the skin surface. This should be taken into account when planning the formulation of optimal skin care products.

Adult↗

[A clinical trial of desired and unwanted effects of topically applied glucocorticosteroids in the human].

Several methods are available for testing the clinical efficacy of topical glucocorticosteroids, some of which only check single parameters relevant to the inhibition of inflammation. These methods include the vasoconstriction assay, the erythema inhibition assays, the psoriasis-plaque assay and the contact sensitization inhibition assay. The methods of testing side-effects include the Duhring chamber assay, the ammonium hydroxide blister assay and the corticoid stratum corneum assay. Provided the most appropriate of these methods are carefully selected, reliable data on the efficacy of topical glucocorticosteroids can be obtained.

Administration, Topical↗

Plasmid content, serotypes, and antimicrobial susceptibility of Neisseria gonorrhoeae strains isolated in Munich in 1987-88.

Eighty-four strains of Neisseria gonorrhoeae isolated in Munich between January 1987 and June 1988 were characterized in terms of their plasmid content, protein I serovar and susceptibility or resistance to four antimicrobial agents. Eighty two percent of the strains belonged to serogroup 1B, the three most prevalent serovars being 1B-1, 1B-2 and 1B-6. Among the serogroup 1A strains, 1A-2 was the commonest serovar. Fourteen strains (16.7%) lacked the 2.6 Md cryptic plasmid, although two of these strains contained the conjugative gonococcal plasmid. Although some degree of resistance to penicillin and tetracycline was noted, all the strains were sensitive to spectinomycin and cefotiam.

Anti-Bacterial Agents↗

[Multi-step increase in resistance of Neisseria gonorrhoeae isolates after repeated in-vitro subinhibitory concentrations of second-generation quinolones].

Five recent gonococcal isolates were exposed to subinhibitory concentrations of several antibiotics in vitro 25 times. In the presence of rifampicin all strains quickly became resistant. In the presence of penicillin, enoxacin and ciprofloxacin, antimicrobial susceptibility also decreased. Here development of resistance, however, corresponded to the multi- and not to the one-step type. It seems remarkable that even at the end of the experiments no strain grew at concentrations of ciprofloxacin exceeding 0.064 mg/l. In conclusion, quick development of resistance need not be expected after the introduction of newer quinolones into the therapy of gonorrhoea on a large scale.

Anti-Infective Agents↗

Liposome preparations: a step forward in topical drug therapy for skin disease? A review.

The production of liposomes, which was described in 1961, soon was claimed to be a useful technology for drug encapsulation. The first preparation (containing a topical antifungal agent), however, was registered only recently. Additional preparations, including some for topical therapy of skin disease, are under clinical investigation. Moreover, a variety of cosmetic products that contain liposomes is available today. In this article we review the literature on liposomes as it pertains to dermatology, including the basic principles of liposome structures and preparations, pharmacokinetics of liposomes and liposome-encapsulated drugs, and the influence on drug activity. Moreover, future applications of liposome preparations are discussed.

Absorption↗

Skin blister fluid levels of ketoconazole during repetitive administration in healthy man.

Ketoconazole administered orally is used in the treatment of superficial and deep mycoses. To evaluate its active concentrations in skin tissue, serum, suction blister fluid (SBF), and cantharides blister fluid (CBF) levels of total and non-protein bound ketoconazole were determined. In general, only the free drug is considered to be the active one. Six healthy subjects received 200 mg once daily for 5 days. Total ketoconazole concentrations were determined by HPLC. The unbound fractions of ketoconazole in SBF (2.3%) and CBF (1.2%) were calculated from plasma protein binding (99.0%). Before the ultimate dose, levels of unbound ketoconazole in SBF and CBF were 0.64 +/- 0.16 and 0.70 +/- 0.25 ng/ml and were thus in accordance with free ketoconazole serum levels (0.52 +/- 0.24 ng/ml; p greater than 0.05). Furthermore, following the ultimate dose, the areas under the blister fluid level-time curves of unbound ketoconazole did not differ from the respective areas under the serum level time curves, thus distribution equilibrium between serum and skin blister fluid was obtained. Peak concentrations of free ketoconazole were (SBF) 8.6 +/- 2.9 ng/ml and (CBF) 8.9 +/- 2.3 ng/ml. Free concentrations in SBF and CBF were far below the MIC values for dermatophytes and Candida ssp. reported in the literature, leaving the concentration-effect relationship of ketoconazole still open for discussion.

Adult↗

Clinical spectrum of oral candidosis and its role in HIV-infected patients.

Oral candidosis is a very frequent diseased state occurring mainly together with severe underlying disease. Clinical manifestation is variable. One can distinguish between oral thrush, denture stomatitis, angular cheilitis, leukoplakia and midline glossitis. Nowadays oral candidosis is also important in connection with HIV-infection. Here the clinical spectrum does not seem to be totally different. Apart from oral thrush (or pseudomembraneous type) a chronic atrophic type, a chronic hyperplastic type, papillary hyperplasia and angular cheilitis are distinguished. Oral candidosis is the most frequent opportunistic infection in HIV-infected patients. Frequency of overt disease is linked to the T4/T8 ratio. In patients with AIDS-related complex oral candidosis seems to be indicative of rapid progression. Candida albicans is the prevailing microorganism. There is, however, a change of biotypes during the course of HIV-infection. There seems to be a selection of certain phenotypes as can be judged from the increasing resistance to 5-fluorocytosine.

Candidiasis, Oral↗