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Biomedical subjects

R Milbradt

Publications and source records attributed to R Milbradt.

At least 37 records · Page 2Linked to original sources

Electron paramagnetic resonance (EPR) imaging in skin: biophysical and biochemical microscopy.

Electron paramagnetic resonance (EPR) is a spectroscopic technique that allows detection of paramagnetic compounds, e.g., free radicals, in skin, and is used for measuring skin membrane fluidity and polarity. EPR imaging is concerned with spatially resolved EPR spectroscopy. We studied EPR images at X-band frequency (9 GHz) in the skin biopsies of hairless mice. Our particular imaging technique utilized a modulated field gradient to obtain cross-sectional images perpendicular to the skin surface. Employing nitroxide free radicals, this approach allows analysis of skin biophysical and biochemical features at the micrometer resolution level. By spin labeling drugs, pharmacokinetic properties of the labeled compound can be monitored in skin. We suggest that EPR imaging has a broad application potential in dermatologic research. In comparison to other spatially visualizing techniques, such as nuclear magnetic resonance (NMR) imaging and ultrasound, EPR imaging has significant advantages, such as high spatial resolution and providing specific biochemical and biophysical information that cannot be obtained by other methods in skin.

Animals↗

Oxidative imbalance in HIV infected patients.

We present an outline of the complex interplay of oxidants and antioxidants in infectious diseases in general, and in particular with reference to the HIV infection, and subsequent opportunistic infections. Viral and opportunistic infections may directly or indirectly cause an imbalance in prooxidant/antioxidant mechanisms and result in generation of increased steady state concentrations of reactive oxidants. In HIV patients a prooxidant state could lead to a self-perpetuation of infection via stimulated expression of genes carrying the virus genome, and subsequently to immunosuppression, and promotion of initiated cells to neoplastic growth.

Antioxidants↗

One- and two-dimensional electron paramagnetic resonance imaging in skin.

EPR imaging with modulated field gradients provides the possibility for obtaining an EPR spectrum in a selected volume. We demonstrate the feasibility of X-band (9.5 GHz) electron paramagnetic resonance (EPR) imaging in skin biopsies of hairless mice. One- (1D) and two-dimensional (2D) EPR images of the persistent free radical di-tertiary-butyl-nitroxide are measured. At a microwave frequency of 9.5 GHz (X-band), 2D images are obtained in skin biopsies with an actual point distinction resolution of 25 microns. In a biological model system, 2D images are measured at L-band frequency (2.0 GHz) with a pixel resolution of 61 microns, and a theoretical spatial resolution of 12.5 microns. In combination with the spin labeling and spin trapping technique, EPR imaging is the most direct approach to analyzing spatial distribution of physicochemical properties in skin, such as membrane fluidity and polarity, as well as detection of free radicals.

Animals↗

[Facial kaposi's sarcoma. Palliative treatment with cryotherapy, intralesional chemotherapy, low-dose roentgen therapy and camouflage].

Facial Kaposi's sarcoma is a severe psychological problem for HIV-infected patients if systemic chemotherapy or interferon therapy is not possible. To help these patients, it is important to offer a palliative treatment that is suitable for outpatients and is not complicated by severe side-effects but still yield satisfactory cosmetic results. A total of 65 patients with 216 facial Kaposi's sarcomas were treated with cryosurgery (92 tumours, 29 patients), intralesional chemotherapy with vincristine (28 tumours, 12 patients), radiotherapy (87 tumours, 15 patients) and camouflage (multiple tumours, 9 patients). Cryosurgery is the treatment of choice for small (less than 1 cm) macular or slightly nodular Kaposi's sarcoma. Larger nodular tumours are better treated by intralesional chemotherapy (single doses of 0.01-0.1 mg vincristine per tumour) or low-dose radiotherapy (3-4 x 4 Gy). These palliative treatment methods are not indicated in cases of rapid tumour progression and dissemination; in such cases, camouflage (covering the tumours with water-resistant make-up) is helpful as a local palliative measure.

Adult↗

[The association of skin fibromas and intestinal polyps: an age-related effect].

To test the association between skin tags and colorectal polyps, 157 consecutive patients (60 men and 97 women, mean age 61.2 [17-92] years) who during their hospitalization had a coloscopy for gastro-enterological indications, underwent independently medical and dermatological examinations. 61 patients (38%) had colorectal polyps, 83 (53%) skin tags; 39 had both (24.8%). Thus the probability of having colorectal polyps was significantly higher for a person with than without skin tags (P = 0.033). But this relationship was entirely age-dependent. Discriminant analysis indicated that in addition to age (F = 15.1) the presence of skin tags (F = 1.2) was only a small additional factor in the recognition of those with colorectal polyps. Skin tags are thus of little help in the diagnosis of polyps in elderly patients.

Adenocarcinoma↗

[Colonic neoplasms and skin fibromas: common determinants and their significance].

To find common factors for colonic-neoplasias and skin-tags, 157 inpatients, who consecutively had a coloscopy because of intestinal complaints, were intensively examined dermatologically. Regression-analyses showed that the number of colonic polyps were age- (p = 3 x 10(-8)) and sex-dependent (1.9 x 10(-2)) and skin-tags had no influence on the number of colonic polyps. The size of colonic polyps also showed a clear age dependency (p = 3 x 10(-8)). The number of skin-tags were dependent on weight (p = 9 x 10(-3)) and age (p = 1.3 x 10(-2)), its size on the interaction of sex and triglyceride-levels (p = 3 x 10(-8)). Discriminant-analyses identified the following factors as important: age and triglyceride-concentration to recognize a patient with colonic polyps; age, positive Haemoccult-test and number of skin-tags to recognize a patient with tubulovillous adenomas or colonic carcinomas. The essential common factor of colonic polyps and skin-tags was the age. For the recognition of a patient with colonic polyps the age was the most essential factor, skin-tags, on the contrary, were unimportant. The association between colonic polyps and skin-tags therefore was merely an effect of age.

Age Factors↗

Anti-human immunodeficiency virus (HIV) drug HOE/BAY946 increases membrane hydrophobicity of human lymphocytes and specifically suppresses HIV-protein synthesis.

The polysulfated polyxylan HOE/BAY946, which has been tested in two pilot studies in ARC/AIDS patients and in asymptomatic HIV carries in Germany, was believed to act by inhibiting virus attachment to the cell. However, the drug was also found to reduce the amount of HIV particles released from infected peripheral blood mononuclear cells (PBMC) in vitro. Furthermore, preincubation of PBMC with the drug led to a partial inhibition of a following HIV infection, suggesting that the drug also affects virus entry. Electron Paramagnetic Resonance (EPR) measurements on uninfected human lymphocytes using 5-proxyl-nonane as spin label demonstrated smaller hyperfine coupling constant (aN) values in the presence of HOE/BAY946 or dextran sulfate 5000. Accordingly, h-1p/h-1H ratios were decreased, indicating increased plasma membrane hydrophobicity and a membrane-stabilizing effect of the drugs. Culture of the chronically HIV-infected monocytic cell line U937/HIV-2D194 in the presence of HOE/BAY946 specifically and drastically reduced the release of virions and the intracellular synthesis of viral proteins as determined by radioimmunoprecipitation and reverse transcriptase assays. In conclusion, although the EPR studies showed a physico-chemical effect on membrane polarity, HOE/BAY946 and dextran sulfate clearly affect processes beyond the cell membrane. Thus, in contrast to previous reports suggesting that polysulfated sugars affect HIV only by inhibiting virus binding to uninfected cells, they clearly inhibit HIV in infected cells as well and appear to have a pleiotropic mode of action. Such drugs may be less likely to result in viral resistance after prolonged application than substances acting only on one step in the life cycle of the virus.

Antiviral Agents↗

Multifunctional analysis of the interaction of anthralin and its metabolites anthraquinone and anthralin dimer with the inner mitochondrial membrane.

We studied the interaction of the antipsoriatic compound anthralin (1.8-dihydroxy-9-anthrone), and its metabolites anthraquinone (1.8-dihydroxy-9.10-anthraquinone) and anthralin dimer (1.8.1'.8'.-tetrahydroxy-10.10'-bis-9[10]-dianthrone) with the inner mitochondrial membrane. Mitochondrial membrane functions such as ubiquinone redox equilibria, redox status of iron sulfur clusters, cyanide-sensitive and cyanide-insensitive oxygen consumption, adenosine triphosphate (ATP) synthesis, ATP hydrolysis, and adenine nucleotide content of mitochondria were analyzed. Anthralin is an inhibitor of mitochondrial oxygen uptake in the presence of ADP and substrate (cyanide-sensitive respiration), inhibits ATP synthesis without affecting ATP hydrolysis, and depletes mitochondria of ATP. Anthralin dimer is a much weaker inhibitor of mitochondrial functions and anthraquinone is almost inactive. Anthralin, but not anthraquinone and anthralin dimer, reverses uncoupler stimulated oxygen consumption, stimulates cyanide-insensitive respiration, reduces mitochondrial ubiquinone-9 and -10 to the corresponding ubiquinols and reduces mitochondrial iron sulfur clusters. Anthralin may induce formation of reactive oxygen species by enhancing autoxidation of mitochondrial components and/or by catalyzed oxidation of anthralin. Taken together, anthralin acts as an electron donor to inner mitochondrial membrane associated redox components, inhibits the electron transport chain, and has an oligomycin-like effect. Anthralin dimer and anthraquinone do not function as electron donors and act by a different reaction mechanism. Respiratory measurements in human keratinocytes revealed similar results as obtained with isolated mitochondria. We suggest that modulation of membrane redox status may be a common concept of anthralin action in target cells such as keratinocytes and neutrophils.

Adenine Nucleotides↗

[Increased expression of the OKM5 antigen in blood monocytes in vitiligo].

In 25 patients suffering from vitiligo, we determined the T-cell profile (OKT3, 4 and 8; anti-Leu7) as well as the peripheral monocytes (OKM5) by means of monoclonal antibodies. Comparing the patients with a control group (n = 8), we found no differences regarding the T-cell count, whereas the expression of OKM5 antigens on peripheral monocytes was significantly elevated in patients with vitiligo.

Adolescent↗

Lobomycosis (keloidal blastomycosis): case reports and overview.

Lobomycosis is a deep fungal disease of the skin without involvement of internal organs or mucous membranes. The disease is characterized by skin nodules and plaques resembling keloid involving the earlobes, distal parts of the upper and lower extremities, and buttocks. In severe cases, large skin areas can be covered by disseminated or grouped and confluent nodules. Most cases are reported from South and Central America. The fungus Paracoccidioides (Glenosporella) loboi is abundant in lesions but is extremely difficult to culture. Lobomycosis is resistant to chemotherapy, but in some cases it can successfully be treated by excision. Although the diagnosis is easily established by its typical clinical, histologic, and microbiological features, it is often misdiagnosed by physicians not familiar with the disease. We describe here five patients and present an overview of this rare disease.

Adult↗

[Soft skin fibromas: study of their importance and diagnostic significance for colonic neoplasms].

The aims of this study were (a) to examine the association of skin tags and colonic polyps and (b) to identify factors influencing skin tags. Therefore, a consecutive series of 157 medical ward patients with gastrointestinal symptoms who underwent colonoscopy underwent dermatological examination. Skin tags were found in 52% of these patients regardless of sex. (a) There was a statistically significant association between skin tags and colonic polyps (P = 0.33). This association, however, was based solely on an age effect. (b) Influencing factors were weight and age for the number of skin tags and the interaction between sex and the concentration of triglycerides for their size. At any given triglyceride concentration, men had larger skin tags.

Aged↗

Ceftriaxone for the treatment of primary and secondary syphilis.

In a multicenter, open, randomized, prospective, comparative study, 28 patients with primary (n = 9) or secondary (n = 19) syphilis were treated with either ceftriaxone or penicillin G. 14 patients received ceftriaxone 4 x 1 g i.m. every 2 days. 14 other patients were treated with penicillin G 1 million IU i.m. daily for 15 days (standard therapy of primary and secondary syphilis). To avoid Herxheimer reaction we applied prednisolone 50-100 mg i.m. before specific treatment. Diagnosis was confirmed by clinical symptoms, dark-field microscopy and serological tests (VDRL titer, TPHA test and 19s-IgM-FTA-abs test or SPHA test). Follow-up examinations during therapy were repeated on days 2, 4, 6 (dark-field microscopy, physical examination) and day 14 (VDRL titer). To evaluate therapeutic efficacy, serological controls were repeated 1, 2, 3, 6 and 12 months after therapy (VDRL, SPHA). In all patients, a marked decline (minimum 2-dilution decrease) in VDRL titer and resolution of clinical symptoms were noted. An adverse reaction was seen in 1 patient of the clemizol-penicillin G group (allergic penicillin exanthema). There were no adverse reactions to ceftriaxone. Summing up, there was no detectable difference in clinical and serological response to syphilis treatment either with ceftriaxone or penicillin G. Ceftriaxone, thus can be regarded as an equivalent alternative to penicillin G in the treatment of primary and secondary syphilis.

Benzimidazoles↗

[Therapy of alopecia areata with diphenylcyclopropenone].

With special regard to practical aspects, we discuss the treatment of alopecia areata by topical immunotherapy with diphenylcyclopropenone. Out of 27 patients treated this way, 10 patients showed good and cosmetically acceptable regrowth of terminal hair; 11 patients showed some regrowth, which was not satisfactory, however, for cosmetic reasons; 6 patients developed no hair growth at all. The complete failure of treatment in the latter cases may possibly be due to the long duration of the alopecia.

Administration, Topical↗

[Therapy of oral hairy leukoplakia with acyclovir].

Oral hairy leukoplakia was treated in six patients with (a) acyclovir (i.v. or p.o.), (b) 0.1% vitamin-A acid solution or (c) human beta-interferon-gel (10(5) I.E./g) in a total of 23 therapeutic courses. In 5/6 patients, acyclovir (7.5 mg/kg every 8 h i.v. or 5 x 400 mg p.o. over 5-10 days) led to partial (n = 1) or complete (n = 4) remission. After 1-6 months, however, the leukoplakia recurred in all cases. Vitamin-A acid solution (n = 3) led to remission in one and to improvement in the others. Human beta-interferon gel (n = 3) had no visible effect. The efficacy of acyclovir is further evidence of the concept that the Epstein-Barr virus is a major cause of oral hairy leukoplakia.

AIDS-Related Complex↗

[Pregnancy dermatoses].

Dermatoses of pregnancy are relatively rare. The terminology becomes increasingly confusing, as only few of these skin eruptions are proved entities. Apart from pruritus gravidarum and herpes gestationis (pemphigoid gestationis), the symptoms of dermatoses of pregnancy should be classified according to polymorphic exanthema, which are characterized by urticarial lesions, or according to prurigo gravidarum, predominantly characterized by excoriated papules.

Dermatitis↗