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Biomedical subjects

K Hoffmann

Publications and source records attributed to K Hoffmann.

At least 127 records · Page 7Linked to original sources

UV transmission measurements of small skin specimens with special quartz cuvettes.

BACKGROUND: The penetration of different wavelengths of UV radiation through human skin is of major importance, especially for the determination of photoprotective properties of sunscreens and UV-protective clothes. OBJECTIVE: In this study we present a new method for the measurement of UV transmission through small skin specimens. METHODS: The transmission measurements were performed by using a UV spectrophotometer with an integrating sphere operating in the wavelength range of 280-390 nm. For the skin samples, special quartz glass cuvettes were developed which allowed measurements for very thin and small skin specimens. Furthermore, the cuvettes prevented dehydration of the specimens and guaranteed, by using an additional diaphragm, that the transmission data were derived solely from the small skin specimen examined. Specimens measuring 8 x 3 mm(2) with a thickness of 0.3 mm (histometric and sonographic control) were taken from the thighs of 10 subjects via shave biopsy. RESULTS: In the UVA range (315-390 nm) we obtained a mean transmission of 4.6% and for the UVB range (280-315 nm) of 0.9%. No significant (p >0.14) difference of UV transmission was found between the individual skin specimens. CONCLUSION: This new method seems to be well suitable for UV transmission measurements of small skin specimens. As UVA radiation has a much deeper penetration depth and in in vivo situations dermal hemoglobin could have an effect on UV penetration, the present method is better suitable for the investigation of UVB-induced biological adaptation mechanisms and the impact of topical agents on UVB transmission of the epidermis.

Aged↗

First non-radioactive assay for in vitro screening of histone deacetylase inhibitors.

Inhibitors of histone deacetylase (HD) are of great potential as new drugs due to their ability to influence transcriptional regulation and to induce apoptosis or differentiation in cancer cells. So far only radioactive enzyme activity assays or in-vivo assays with subsequent electrophoresis and immunoblotting existed to study the activity of HD and potential inhibitors. To aid in the search of new inhibitors, a non-radioactive screening assay was sought and we have previously succeeded in establishing this for the first time. The assay uses an aminocoumarin derivative of an omega-acetylated lysine as substrate for the enzyme. Here we report full experimental details, the evaluation of other potential substrates, and comparative analysis of various inhibitors. This advantageous method should have an impact on further developments in the field.

Aminocaproic Acid↗

Abnormalities of the photoreceptor-bipolar cell synapse in a substrain of C57BL/10 mice.

PURPOSE: A preferential loss of ERG b-wave was detected in a substrain of C57BL/10 mice. Electroretinographic and histologic techniques were used to investigate this hitherto unknown retinopathy. METHODS: ERGs were obtained from normal and affected C57BL/10. C57BL/6 mice served also as controls. a-Wave and c-wave analyses were performed. Microscopic investigations were done at two different ages. RESULTS: In the scotopic ERG, a severe reduction of the b-wave amplitude could be observed, whereas the a-wave was only moderately attenuated ("negative ERG"). With age, the a-wave amplitude further decreased, but the rate of reduction was comparable to normals. Oscillatory potentials were severely altered, and the photopic ERG was absent. The ERG c-wave was comparable to normal. ERG a-wave analysis also revealed a reduced maximum amplitude, but no significant difference of receptor sensitivity. Light microscopy revealed a thinning of all retinal layers but mostly of the outer plexiform layer. The number of photoreceptor nuclei was reduced by one third. Electron microscopy revealed a profound loss of ribbon-shaped synapses between rod and rod-bipolar cells and severely abnormal ribbons in the case of cones. CONCLUSIONS: The so-called negative ERG was associated with alterations in the synaptic layer between rods and rod bipolars. The absent cone ERG may be due to the altered cone-on-bipolar synapses. The overall thinning of the retina as well as the moderately reduced scotopic a-wave amplitude remain unexplained.

Animals↗

[Quality of life in the course of deinstitutionalisation-- part IV of the Berlin Deinstitutionalisation Study].

As part of the Berlin Deinstitutionalisation Study, quality of life was assessed in 142 patients at two points of time. Discharged patients were reassessed one year after discharge. Patients who stayed in hospital were reinterviewed 1 1/2-2 years after the initial assessment. Discharged patients had more leisure activities, more often a "good friend", and more frequent social contacts. They were less often victim of a crime within the last year. In a cross-sectional comparison, they were significantly more satisfied with their life than patients who were still in hospital. In the latter group, only satisfaction with mental health improved significantly between first and second interview. Discharged patients became significantly more satisfied with their life in general, with leisure activities, with accommodation, and with mental health between initial assessment and follow-up. The findings demonstrate an improvement of quality of life in long-term hospitalised patients after discharge.

Adult↗

A non-isotopic assay for histone deacetylase activity.

Inhibitors of histone deacetylase (HD) bear great potential as new drugs due to their ability to modulate transcription and to induce apoptosis or differentiation in cancer cells. To study the activity of HD and the effect of potential inhibitors in vitro so far only radio-active assays have existed. For the search of new inhibitors and for the use in HD identification and purification we established a simple, non-radioactive assay that allows screening of large numbers of compounds. The assay is based on an aminocoumarin derivative of an Omega-acetylated lysine as enzyme substrate.

Acetylation↗

Adenoviral gene transfer of the human V2 vasopressin receptor improves contractile force of rat cardiomyocytes.

BACKGROUND: In congestive heart failure, high systemic levels of the hormone arginine vasopressin (AVP) result in vasoconstriction and reduced cardiac contractility. These effects are mediated by the V1 vasopressin receptor (V1R) coupled to phospholipase C beta-isoforms. The V2 vasopressin receptor (V2R), which promotes activation of the Gs/adenylyl cyclase system, is physiologically expressed in the kidney but not in the myocardium. Expression of a recombinant V2R (rV2R) in the myocardium could result in a positive inotropic effect via the endogenous high concentrations of AVP in heart failure. METHODS AND RESULTS: A recombinant adenovirus encoding the human V2R (Ad-V2R) was tested for its ability to modulate the cardiac Gs/adenylyl cyclase system and to potentiate contractile force in rat ventricular cardiomyocytes and in H9c2 cardiomyoblasts. Ad-V2R infection resulted in a virus concentration-dependent expression of the transgene and led to a marked increase in cAMP formation in rV2R-expressing cardiomyocytes after exposure to AVP. Single-cell shortening measurements showed a significant agonist-induced contraction amplitude enhancement, which was blocked by the V2R antagonist, SR 121463A. Pretreatment of Ad-V2R-infected cardiomyocytes with AVP led to desensitization of the rV2R after short-term agonist exposure but did not lead to further loss of receptor function or density after long-term agonist incubation, thus demonstrating resistance of the rV2R to downregulation. CONCLUSIONS: Adenoviral gene transfer of the V2R in cardiomyocytes can modulate the endogenous adenylyl cyclase-signal transduction cascade and can potentiate contraction amplitude in cardiomyocytes. Heterologous expression of cAMP-forming receptors in the myocardium could lead to novel strategies in congestive heart failure by bypassing the desensitized beta-adrenergic receptor signaling.

Adenoviridae↗

[Phototherapy in severe atopic dermatitis. Comparison between current UVA1 therapy, UVA1 cold light and combined UVA-UVB therapy].

Severe atopic dermatitis, especially when involving the face, does not respond well to conventional therapy. In the present prospective randomized trial, we compared therapeutic efficiency of medium-dose UVA1, medium-dose cold light UVA1 (15 treatment courses with 50 J/cm2 each) and combined UVA-UVB phototherapy. Four (13.3%) of 30 UVA1 treated patients, one (3.4%) of 30 UVA1 cold light treated patients and three (30%) of 10 patients treated with combined UVA-UVB discontinued therapy course before finishing treatment protocol because skin status did not improve or even deteriorated. In the other patients treated over a period of three weeks, skin status improved significantly or even cleared completely in 80.8% of UVA1 treated and in 89.7% of UVA1 cold light treated patients resulting in a significant decrease of the SCORAD-Score (UVA1 group from 68.6 +/- SD 10.9 to 29.8 +/- SD 7.1 and UVA1 cold light group from 72.5 +/- SD 13.4 to 23.8 +/- SD 11.6; p < 0.05 each). In the UVA-UVB treated group, the SCORAD-Score also decreased (from 71.0 +/- SD 9.4 to 41.6 +/- 10.5), but significantly less than in both UVA1 treated groups (p < 0.05 each). Four weeks after completing therapy UVA1 treated patients showed a prolonged therapy benefit as compared to UVA-UVB treated patients. Plasma levels of eosinophil cationic protein and soluble interleukin-2 receptor significantly decreased under UVA1 phototherapy but not under UVA-UVB therapy. Compared to conventional UVA1 phototherapy, UVA1 cold light phototherapy showed advantages due to the absence of potentially proinflammatory effects based on temperature-induced increase of skin blood flow (quantified by Laser doppler scanning) and increased sweat production (determined by the patient using a visual analog scale).

Adolescent↗

[Depression and suicidal intentions as a side effect of high dosage interferon-alpha therapy--two cases].

Adjuvant therapy with interferon for malignant melanoma causes neurotoxic side effects such as depression. The biochemical mechanisms are unknown. We report two cases with both depression and amnesia. In one case, attempted suicide was accompanied by 7 h of amnesia. The diagnostic classification and possible explanations for the amnesia secondary to interferon therapy are reviewed.

Adjuvants, Immunologic↗

[Prevalence of psychological symptoms in dermatologic patients of an acute clinic].

There is a lot of information in the literature about psychological disturbances in somatic diseases. For dermatological patients such data are not available. In early spring 1998 we studied the psychological changes in 247 hospitalized patients in the dermatological department of the Ruhr University Bochum. We used the German version of the internationally accepted Hospital Anxiety and Depression Scale. We found the prevalence of psychological alterations ranged between 25.9% and 31%. The prevalence of psychological disturbances was a little higher than that seen in oncological, cardiological or neurological patient populations. Surprisingly skin cancer patients were less affected than patients with chronic inflammatory or angiological diseases. These results underline the necessity of improved psychological therapeutical strategies which must be standardized and evaluated.

Adult↗

[Correlation between epiluminescence microscopy characteristics of malignant melanomas and Clark's level of invasion].

Many epiluminescence microscopy (ELM) characteristics of malignant melanoma support the differential diagnosis of pigmented skin tumors. A preinvasive evaluation of level of invasion would be valuable for planning the excision margins. Since sonography for tumor thickness measurement is rarely available in a practice we searched for specific ELM criteria correlating with Clark's level of invasion. In our retrospective study of 120 malignant melanomas of 30 ELM features were studied for their correlation and the association was significant for 15 features.The following criteria were found only in level III-IV melanomas: intralesional horizontally elongated blood vessels, spontaneous microhemorrhages, plaster-of-Paris-like lacunae, grey-blue/yellowish-brown/reddish saccular pattern and eccentric nodes (reddish, livid, blue). 7 characteristics were predominantly found in level III-IV melanomas and seldom in "thin" melanomas (level I-II): deeply localized gray-blue/-brown fragmentary network, whitish-opaque septa, whitish- or bluish-opaque veil, negative pigmented network, areola with evenly arranged capillaries, polymorphic capillaries. Perivascular melanophages, eccentric dark blotches, pseudotrabeculae of melanophages and greyish-blue annular perifollicular pigmentations were the most significant association of ELM criteria in "thin" melanomas (level I-II). Epiluminescence microscopy is not only a tool for the differentiation of melanocytic lesions but also for a preinvasive evaluation of Clark's level of invasion.

Adult↗

[Tazarotene increases the antipsoriatic effect of dithranol in chronic psoriasis].

We examined whether it is possible to increase the antipsoriatic action by combining dithranol with a retinoid (tazarotene). In a randomized, open, prospective study with 50 psoriatic patients (22 females, 28 males, PASI>10) the antipsoriatic effectiveness of dithranol monotherapy to was compared combined therapy with dithranol and retinoid. The combination dithranol/retinoid (collective 2, reduction of the PASI from 17,2 to 2,8) revealed a significantly faster healing than the dithranol monotherapy (collective 1, reduction of the PASI from 18,5 to 4,8). The irritation of the combination therapy as evaluated with clinical score and laser doppler imaging was increased. Anti-psoriatic effectiveness of dithranol can be increased by combining it with tazarotene.

Anthralin↗

Treatment of patients with low-risk myelodysplastic syndromes using a combination of all-trans retinoic acid, interferon alpha, and granulocyte colony-stimulating factor.

Used as single agents, ATRA, G-CSF, and IFN-alpha have shown a moderate benefit in patients with low-risk MDS, with a response rate of 10%. The aim of the present study was to evaluate the efficacy of a combination of these agents. The effect on hemoglobin (Hb), platelets, and absolute neutrophil count (ANC), as well as on transfusion frequency, was examined in 25 patients with MDS (11 RA, four RARS, eight RAEB, two CMML). The median age was 61 years (range 44-81), and the male/female ratio was 14/11. Treatment consisted of ATRA at 25 mg/m2/day p.o. for months 1, 3, 5, 7, 9, and 11, IFN-alpha at 1.5 MIU twice a week s.c. for 52 weeks, and, in patients with initial ANC <500/microl, G-CSF at 100-480 microg daily s.c. according to the degree of ANC. The duration of therapy was scheduled for 12 months. Two patients achieved ongoing CR (+19 months; +16 months), one patient with RA after 3 months and one with CMML after 7 months of treatment. In all patients, the mean ANC increased significantly from 1400+/-200/microl before the start of therapy to 3500+/-600/microl at the end of treatment (p=0.025). In two patients an increase of Hb was observed, and one patient ceased to require transfusions. In an additional patient with RA and 5q-syndrome, the platelet count normalized following administration of ATRA/IFN-alpha, increasing from 89,000/microl to 293,000/microl. The eight RAEB patients were nonresponders. We conclude that therapy with ATRA, IFNalpha, and G-CSF is effective in approximately 35% of low-risk MDS patients (in this study: six of 17) and may induce complete remission in individual cases.

Adult↗

Medium-dose UVA1 cold-light phototherapy in the treatment of severe atopic dermatitis.

BACKGROUND: Recently, conventional high-dose UVA1 phototherapy (340-400 nm) has been shown to be more effective than combined UVA-UVB therapy in the treatment of severe atopic dermatitis (AD). However, there are limitations of this treatment, such as intense sweating caused by the immense heat load during therapy and the high cumulative UVA1 doses that are required. For this reason, lavish UVA1 equipment was developed containing an advanced filtering and cooling system resulting in almost complete absence of heat load and sweating during therapy. OBJECTIVE: In this study we compared the monotherapeutic efficacy of conventional medium-dose UVA1, medium-dose UVA1 cold-light, and combined UVA-UVB phototherapy in the treatment of severe AD. METHOD: The study involved 120 patients with severe AD. Fifty patients each received conventional UVA1 or UVA1 cold-light phototherapy (15 days, 50 J/cm(2)/day), and 20 patients were treated with combined UVA-UVB (15 days, minimal erythema dose dependent). Severity of AD was scored by means of the SCORAD score, and clinical improvement was additionally monitored by serologic cytokine markers. RESULTS: Six (12%) of 50 patients treated with UVA1, 2 (4%) of 50 patients treated with UVA1 cold-light therapy, and 4 (20%) of 20 patients treated with combined UVA-UVB therapy discontinued treatment prematurely because of an unsatisfactory clinical outcome or adverse reactions. Skin status improved or even cleared completely in 77.3% of the patients treated for 3 weeks with conventional UVA1 therapy and in 85.4% of the patients treated for 3 weeks with UVA1 cold-light therapy, resulting in a significant decrease in the SCORAD score in both UVA1 groups (P <.05 each). In the group treated with combined UVA-UVB, the SCORAD score also decreased but significantly less than in both groups treated with UVA1 photo-therapy (P <.05 each). At follow-up after 4 weeks, the patients treated with UVA1 displayed a more prolonged therapeutic benefit than the patients treated with UVA-UVB therapy. Plasma levels of soluble interleukin 2 receptors and soluble interleukin 4 receptors significantly decreased under both UVA1 and UVA1 cold-light phototherapy but not under combined UVA-UVB phototherapy. CONCLUSION: Our study demonstrates that medium-dose UVA1 cold-light phototherapy displays advantages compared with conventional UVA1 phototherapy caused by the almost complete absence of heat load and intense sweating and is more effective than UVA-UVB phototherapy in the treatment of severe AD.

Adolescent↗

Identification of hemifield single trial PVEP on the basis of generalized dynamic neural network classifiers.

This paper is concerned with the application of generalized dynamic neural networks for the identification of hemifield pattern-reversal visual evoked potentials. The identification process is performed by different networks with time-varying weights using signals from different electrode positions as external inputs. Since dynamic neural networks are able to process time-varying signals, the identification of the stimulated hemiretinae is performed without feature extraction. The performance of the method presented is compared with a reference method based on the values of instantaneous frequency at the occipital electrode positions at P100 latency.

Adult↗

Blood flow compared in benign melanocytic naevi, malignant melanomas and basal cell carcinomas.

Histologically, increasing malignancy is reflected by increased tumour vascularization. We therefore assessed whether laser Doppler perfusion imaging might allow differentiation between different types of skin tumour. The perfusion patterns of 27 melanocytic naevi, 16 basal cell carcinomas and six malignant melanomas were examined with a laser Doppler perfusion imager before excision for precise diagnosis. Malignant melanomas were significantly more perfused than basal cell carcinomas and tended also to be more so than melanocytic naevi. Further, for the first time, the perfusion pattern of the entire tumour area was visualized two-dimensionally; it was higher in the centre of the tumours than at the periphery for malignant melanomas and melanocytic naevi but was the same throughout for basal cell carcinomas. Laser Doppler perfusion imaging can thus provide information to assist in the differential diagnosis of skin tumours. In addition, with increases in resolution of the technique such data may well become steadily more useful in the future.

Basal Cell Carcinoma↗

[Ranking of 20 MHz sonography of malignant melanoma and pigmented lesions in routine diagnosis].

PURPOSE: Eleven dermatology clinics from all over Germany took part in our multicenter prospective study with the aim of evaluating 20 MHz sonography in the preoperative diagnosis of malignant melanomas and other pigmented skin tumours. It was to be assessed how effective sonographic measurement of thickness would compare to histology and the clinical palpation of tumour thickness and also the significance of differential diagnosis in sonography of malignant melanomas. METHOD: The prospective multicenter study proceed as follows. To the end of August 1997 264 patients with a primary malignant melanoma and 417 patients with benign skin tumours were examined via 20 MHz sonography. Two different examiners estimated the clinical thickness of the tumour by palpation. The tumour was then excised and examined for postoperative correlation with the histology sections. RESULTS: The final results showed good correlation between the histological and sonographic estimation of tumour thickness (r = 0.97). Estimation of tumour thickness by palpation showed no correlation with the histology (r = 0.59). Most of the benign (44%) and malignant tumours (38.7%) were spindle shaped. There was no significant difference between the benign and malignant tumour groups in relation to the sonographic presented shapes or echo signs. No different diagnosis could be made. CONCLUSION: The technique of high frequency sonography in relation to preoperative diagnosis of malignant melanomas has high priority. In contrast to clinical estimation of tumour thickness, sonography provided a good correlation to histology. The effectiveness of sonography with regard to the valence of the skin tumours is limited and there is no possibility of differentiating between malignant and benign tumours from the morphological face value. Hence, there is a demand for developing a 150 MHz apparatus which will be able to supply evidence regarding the valence of skin tumours.

Diagnostic Tests, Routine↗