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Biomedical subjects

K Hoffmann

Publications and source records attributed to K Hoffmann.

447 records · Page 25Linked to original sources
PubMedDate not supplied

Combined treatment with calcipotriol ointment and low-dose ultraviolet A1 phototherapy in childhood morphea.

Various therapies for morphea have been used with limited success, including ones with potentially hazardous side effects. When morphea occurs in childhood it may lead to progressive and long-lasting induration of the skin and subcutaneous tissue, growth retardation, and muscle atrophy. We report an open prospective study in which the efficacy of a combined treatment with calcipotriol ointment and low-dose ultraviolet A1 (UVA1) phototherapy in childhood morphea was investigated. Nineteen children (mean age 8.5 years, range 3-13 years) with morphea were exposed to UVA1 (340-400 nm) phototherapy at a dose of 20 J/cm(2) four times a week for 10 weeks. Forty phototherapy sessions resulted in a cumulative dose of 800 J/cm(2) UVA1. In addition, calcipotriol ointment (0.005%) was applied twice a day. After 10 weeks, palpation and inspection showed a remarkable softening and repigmentation of formerly affected skin resulting in a highly significant (p < 0.001) decrease of the mean clinical score from 7.3 +/- 0.9 at the beginning to 2.4 +/- 0.9 (relative reduction 67.1%) at the end of combined therapy. Our results indicate that a combined therapy with calcipotriol ointment and low-dose UVA1 phototherapy is highly effective in childhood morphea. Further controlled studies are necessary to investigate whether this combined therapy is superior to UVA1 phototherapy alone.

Adolescent↗
PubMedDate not supplied

The German Environmental Survey 1990/92 (GerES II): primary predictors of blood cadmium levels in adults.

As part of the representative Environmental Survey in Germany in 1990-1992, investigators determined cadmium levels in blood provided by 3,965 subjects aged 25-69 yr. The investigators considered approximately 150 variables (i.e., demographics, household and occupational characteristics, environmental exposures, smoking habits, frequency of food consumption, and additional life-style features) as potential predictors in multivariate regression analysis. On the basis of the results of multivariate regression analysis, the authors derived 2 slightly different models for the prediction of blood cadmium levels in populations from West and East Germany. Both models included 3 primary predictors of blood cadmium levels. The 2 models explained 51.3% and 61.2% of the observed variance in blood cadmium levels in West and East Germany, respectively. The most important predictor was a specific indicator for smoking habits, which was determined from a separate mathematical model. In this model, the effect of smoking was considered, and the model accounted for the biological half-life of cadmium in blood.

Adult↗
PubMedDate not supplied

Photoperiodic influence on the morphology and the androgen receptor level of the ventral prostate gland and seminal vesicles of the Djungarian hamster (Phodopus sungorus).

The influence of long (light:darkness LD 16:8) and short (LD 8:16) photoperiods on the morphology of the ventral prostate gland and the seminal vesicles of the Djungarian hamster was investigated. At LD 8:16, the wet weight of the glands was reduced to 15-20% of the values found in animals living in LD 16:8 conditions, the protein content was reduced to 3-4%. The glands showed distinct signs of atrophy and inactivity under short-day conditions. The androgen receptor levels were determined in both accessory sex glands. The receptor levels were comparable in both glands; the absolute values related to the whole glands remained about constant in animals living in long and short photoperiods despite a reduction of the androgen levels in short photoperiods.

Animals↗
PubMedDate not supplied

Plasma levels of 8-methoxypsoralen following PUVA-bath photochemotherapy.

Administration of 8-methoxypsoralen (8-MOP) in a dilute bath water solution is an effective therapeutic alternative to oral PUVA therapy, avoiding systemic side effects, offering better bioavailability of the psoralen and requiring much smaller amounts of UVA for induction of therapeutic effects. To obtain exact data about the percutaneous absorption of 8-MOP during a psoralen bath, the plasma levels of the drug were determined in 26 patients with different skin diseases by a reverse high-performance liquid chromatographic method. Fifteen patients receiving oral PUVA therapy (0.8 mg 8-MOP/kg body weight) served as a positive control group. Bath solutions were prepared by diluting 15 ml of 0.5% stock solution of 8-MOP in 150 l of bath water (0.5 mg/l, 37 degrees C). Blood samples were drawn from patients 5, 30, 60, 120 and 180 min after the bath. In the oral PUVA group, blood samples were obtained 1 1/2 h after administration of the drug. In 23 of 26 patients, 8-MOP levels were undetectable in every blood sample. After 30 min, two patients showed detectable levels of 8-MOP (5 ng/ml, 7 ng/ml), while 60 min after the PUVA bath 8-MOP was detectable in only one volunteer (5 ng/ml). In patients receiving oral 8-MOP therapy, serum levels varied between 45 and 360 ng/ml 1 1/2 h after drug administration. Our data confirm extremely low 8-MOP levels resulting from 8-MOP bath water treatments and provide confirmation of the absence of systemic side effects in patients who are undergoing PUVA-bath therapy.

Administration, Oral↗
PubMedDate not supplied

UV transmission and UV protection factor (UPF) measured on split skin following exposure to UVB radiation--correlation with the minimal erythema dose (MED).

In this study the ultraviolet (UV) transmission of split skin exposed to UVB radiation and of non-exposed skin was compared in the 280-390 nm wavelength range and quantified. In addition, the correlation between the increase in the minimal erythema dose (MED) associated with a defined exposure to UVB and the ultraviolet protection factor (UPF) calculated from the transmission data was investigated. The study population consisted of 12 patients. Two pieces of split skin of the same thickness (0.3 mm) were taken from the right thigh of each patient. One specimen was removed from an area of non-exposed healthy skin and the other from an area which had been exposed to UVB radiation for a period of 12 days in which the initial dose of 1/3 MED was raised by 1/3 MED every 4 days. The split skin specimens were stretched over a special frame; subsequently, the UV transmission was determined with a spectrophotometer. The mean values obtained for UV transmission were all significantly below the initial data for non-exposed split skin. In the UV range of 280--390 nm, the transmission measured in the exposed specimens was 49.1% of the value measured in the non-exposed split skin (P<0.05). The corresponding values for the UVA range (315--390 nm) and the UVB range (280--315 nm) were 50.1% and 29.5%, respectively (P<0.05), based on the initial transmission data obtained from non-exposed skin. The clinical determination of MED after 12 days of exposure to UVB yielded mean values that were 3.2 times the initial values. Moreover, the mean UPFs calculated from the transmission data measured at the end of the 12-day exposure period were also about three times the initial values. The present study has thus established a significant correlation between the clinical MED values and the UPFs calculated from the transmission data measured following exposure to UVB.

Adult↗
PubMedDate not supplied

Differences in the two-dimensionally measured laser Doppler flow at different skin localisations.

The cutaneous microcirculation shows a significant heterogeneity. With high-resolution two-dimensional laser Doppler perfusion imaging (LDPI), spatial and temporal reproducible perfusion measurements can be reached. The objective of this study was the quantification of skin perfusion in 20 defined skin areas with LDPI, in 60 healthy young and old volunteers. The perfusion of the face was significantly higher than that of the trunk and extremities. The highest perfusion values were seen at the lips, 1.47 arbitrary units (AU), followed by the chin (0.99 AU), the nose (0.95 AU), the forehead (0.73 AU) and the cheek (0.72 AU). Mean perfusion, between 0.40 and 0.49 AU, was seen at the extremities and at the trunk. The lowest perfusion was found at the bottom (0.37 AU), on the back of the foot (0.36 AU) and on the soles (0.31 AU). There was a tendency to show higher perfusion values in men than in women (0.60 +/- 0.31 vs. 0.53 +/- 0.26 AU). Age-related differences in perfusion could not be demonstrated. In the evaluation of the perfusion of pathological skin, regional perfusion differences must be considered, whereas moderate age or gender differences between different investigation groups can be tolerated.

Adult↗
PubMedDate not supplied

The effect of the base on the kinetics of action of the capsaicinoid nonivamide: evaluation with a hyperemic test.

Because of their selective receptor-mediated action on cutaneous nociceptive C-fibers, the interest in capsaicinoids as topical analgetic drugs has been constantly growing over the past years. Knowledge of the pharmacokinetics seems particularly important for potential future clinical applications. Therefore, the aim of the present study was to investigate the influence of the type of preparation on the time course of action of the capsaicinoid nonivamide monitored by the axon-reflex-induced hyperemic action and area of erythema. Sixteen healthy subjects were included in the study. The hyperemic responses after application of nonivamide in an oil-in-water (O/W) emulsion and in a water-free ointment were assessed both by laser Doppler perfusion imaging and planimetry after 0, 15, 30, 45, 60, 120 and 240 min. They were compared with the reaction after application of the nicotinic ester nicoboxil and a combination of nonivamide and nicoboxil in the same preparations. Applied as a water-free ointment, nonivamide showed a slow onset of hyperemic action, reaching its maximum 45 min after application. When applied as an O/W emulsion, however, the increase in effect was high, reaching its maximum already after 30 min. Application of the nicoboxil preparations revealed a clearly lesser influence of the base regarding the onset of maximum effect. The combination of both substances showed an additive effect for both bases, and a maximum effect was found already after 15 min with both the water-free ointment and the O/W emulsion base. In conclusion, the results of the present study show that there appears to be a strong influence of the vehicle on the kinetics of action of capsaicinoids, and that the hyperemic test used in this paper is very useful for the quantitative determination of the pharmacokinetic properties of capsaicinoids. Moreover, the C-fiber-stimulating effect of capsaicinoids can, at least in part, be enhanced by combination with a nicotinic ester, even though these substances have no direct effect on the C-fibers.

Adolescent↗
PubMedDate not supplied

Molecular farming of recombinant antibodies in plants.

'Molecular farming' is the production of recombinant proteins in plants. It is intended to harness the power of agriculture to cultivate and harvest transgenic plants producing recombinant therapeutics. Molecular farming has the potential to provide virtually unlimited quantities of recombinant antibodies for use as diagnostic and therapeutic tools in both health care and the life sciences. Importantly, recombinant antibody expression can be used to modify the inherent properties of plants, for example by using expressed antipathogen antibodies to increase disease resistance. Plant transformation is technically straightforward for model plant species and some cereals, and the functional expression of recombinant proteins can be rapidly analyzed using transient expression systems in intact or virally infected plants. Protein production can then be increased using plant suspension cell production in fermenters, or by the propagation of stably transformed plant lines in the field. Transgenic plants can be exploited to produce organs rich in a recombinant protein for its long-term storage. This demonstrates the promise of using transgenic plants as bioreactors for the 'molecular farming' of recombinant therapeutics, blood substitutes and diagnostics, such as recombinant antibodies.

Antibodies↗
PubMedDate not supplied

Antibody production by molecular farming in plants.

"Molecular farming" is the production of pharmaceutical proteins in transgenic plants and has great potential for the production of therapeutic anti-cancer antibodies and recombinant therapeutic proteins. Plants make fully functional recombinant human or animal antibodies. Cultivating transgenic plants on an agricultural scale will produce almost unlimited supplies of recombinant proteins for uses in medicine. Combinatorial library technology is a key tool for the generation and optimisation of therapeutic antibodies ahead of their expression in plants. Optimised antibody expression can be rapidly verified using transient expression assays in plants before creation of transgenic suspension cells or plant lines. Subcellular targeting signals that increase expression levels and optimise protein stability can be identified and exploited using transient expression to create high expresser plant lines. When high expresser lines have been selected, the final step is the development of efficient purification methods to retrieve functional antibody. Antibody production on an industrial scale is then possible using plant suspension cell culture in fermenters, or by the propagation of stably transformed plant lines in the field. Recombinant proteins can be produced either in whole plants or in seeds and tubers, which can be used for the long-term storage of both the protein and its production system. The review will discuss these developments and how we are moving toward the molecular farming of therapeutic antibodies becoming an economic and clinical reality.

Animals↗
PubMedDate not supplied

Re-entrainment of circadian rhythms after phase-shifts of the Zeitgeber.

To describe anabrupt shift of the Zeitgeber sufficiently, it is necessary to indicate whether the phase has been advanced or delayed, for how many hours it has been shifted, and what part of the Zeitgeber has been lengthened or shortened respectively. The entrained circadian system usually follows a shift of the Zeitgeber in the same direction and by an equal amount. However, there can be exceptions to both of these rules: a) an instantaneous 12-h shift of a (symmertric) Zeitgeber always represents a delya (= doubling of one-half of its period). In contrast to this, the gradual re-entrainment of the circadian system can be accompalished by either advances or by delays (Fig. 2), it can occur in both dirctions simultaneously by splitting the rhythmic variable (Fig. 1),or it can represent an apparent advance not distinghushable from a delay ( Fig. 6); b) after complietion of re-entraiment, the phase-angle difference psi between organism and Zeitgeber an differ systematically from the pre-shift psi-value...

Activity Cycles↗
PubMedDate not supplied

The significance of Tenascin-C serum level as tumor marker in squamous cell carcinoma of the head and neck.

BACKGROUND: Tenascin, an extracellular matrix glycoprotein, is transiently present in embryonic tissue, in benign granulation tissue, but also in several highly anaplastic tumors like fibrosarcoma, melanoma and squamous cell carcinoma of the skin. This study was performed to validate elevated Tenascin serum levels as a possible marker for head and neck squamous cell carcinomas (HNSCC). PATIENTS AND METHODS: Tenascin serum levels were evaluated in patients with primary (n = 92) and with recurrent (n = 28) HNSCC. Patients with benign, non inflammatory ear, nose and throat diseases (n = 16) served as the control. The Tenascin serum levels were measured by ELISA (Aventis). RESULTS: Serum Tenascin concentrations of patients with benign ENT diseases ranged between 0.37 and 2.19 micrograms/ml (n = 16, mean +/- SD: 1.23 +/- 0.59 micrograms/ml), of patients with HNSCC (primary diagnosis) between 0.05 and 8.75 micrograms/ml (n = 92, mean +/- SD: 1.81 (1.36 micrograms/ml) and of patients with recurrent HNSCC between 0.53 and 10.0 micrograms/ml (n = 28, mean +/- SD: 2.78 +/- 2.2 micrograms/ml). CONCLUSION: We found a significant elevation of Tenascin serum levels only in patients with higher tumor stages (T4/UICC4) (p < 0.01/p < 0.1) or recurrent disease compared to Tenascin serum levels in healthy controls. Thereby Tenascin serum levels cannot be used clinically as a routine serum marker for the control of head and neck cancer. Further investigations are necessary to evaluate whether the measurement of Tenascin levels as tumor markers could offer additional information to the clinical outcome of patients with HNSCC.

Biomarkers, Tumor↗
PubMedDate not supplied

Immunohistochemical localization of neuropeptide Y in nerves of the male genital tract of the photoperiodically responsive Djungarian hamster, Phodopus sungorus.

Neuropeptide Y (NPY) was demonstrated by immunohistochemistry in nerves of the male genital tract of Phodopus sungorus at long (LD 16:8) und short (LD 8:16) photoperiods. No immunoreactive nerve fibres could be demonstrated in the testis, caput and corpus epididymidis and the ventral prostate gland. Dense networks of NPY-containing nerve fibers were demonstrated in the smooth muscle layer of the sperm-transporting duct, beginning in the cauda epididymidis with increasing density towards the distal part of the ductus deferens, and in the smooth muscle layer of the seminal vesicles. At short photoperiods, the density of the NPY-containing nerve plexus decreased only in the smooth muscle layer of the ductus deferens. A "trophic" influence of the large smooth muscle cells of the ductus deferens on their nerves not only in regard to their noradrenaline, but also on their NPY content is discussed.

Animals↗
PubMedDate not supplied

Influence of long and short photoperiods on the morphology and androgen receptor levels of the epididymis and the ductus deferens of Phodopus sungorus.

The photoperiodic influence (LD 16:8 long photoperiod, LD 8:16 short photoperiod) on the morphology and the androgen receptor level of the epididymis and the ductus deferens of Phodopus sungorus was investigated. Under short day-conditions, the wet weight of the epididymis is reduced to 5-6%, the diameter of the epididymal duct and of its lumen are reduced, the height of the epithelium and the thickness of the smooth muscle layer are increased. Number and size of epithelial and smooth muscle cells are not changed, no atrophy of the smooth muscle cells is found. The loss in wet weight during short photoperiods is discussed in relation to the loss of stored sperm and luminal fluid. The wet weight of the ductus deferens is decreased to about 30% at short photoperiods, the total length of the organ, its diameter and the luminal diameter are decreased. The height of the epithelium is slightly, and the thickness of the smooth muscle layer is strongly, reduced, the latter due to an enormous atrophy of the smooth muscle cells. The androgen receptor content of the epididymis (per pair of organs) is reduced to about 5%, that of the ductus deferens to about 10% of the values found at long photoperiods, indicating a significant loss of androgen receptors with low circulating androgen levels.

Animals↗