Search PubMed⌕ Search

Biomedical subjects

G Schuler

Publications and source records attributed to G Schuler.

At least 37 records · Page 2Linked to original sources

[Malignant melanoma. Diagnosis and therapy].

In Germany, 6100 women and 5300 men contract a malignant melanoma of the skin every year. The chances of being cured are good in the early stages of the disease, but the average survival following distant metastasis is only 6 to 9 months. Therefore, early diagnosis is crucial, particularly as the skin is, by nature, a readily accessible organ. The introduction of epiluminescence microscopy has increased diagnostic accuracy significantly. In cases of doubt, complete excision of the suspect pigmented lesion is always advisable. A light skin type, presence of numerous naevi, genetic predisposition (familial history) and increased UV exposure are considered as risk factors. As a rule, adjuvant imunotherapy with interferon-alphais recommended in high-risk patients. A multidisciplinary approach consisting of surgery, radiotherapy, chemotherapy and immunotherapy has proved beneficial in advanced stages of metastasis.

Combined Modality Therapy↗

[Physical activity].

There are a total of 30 publications regarding the role physical exercise in primary prevention of coronary artery disease, nearly a quarter of a million patients have participated in these studies. The average observation time reaches 10 years. According to the guidelines of the ACC/AHA Task Force this is the basis for the evidence/recommendation class I. The benefit derived from this treatment considerably exceeds the risk; thus, there is no need for additional studies. A great number of population-based risk factors were evaluated; in several randomized studies and meta-analyses concordant results were achieved with respect to direction and degree of the therapeutic effect (Level B).

Clinical Trials as Topic↗

Estrogen receptor beta (ERbeta) is expressed differently from ERalpha in bovine placentomes.

The functions of placental estrogens in cattle are still poorly understood. In order to investigate a putative role as local regulators of placental growth, differentiation and functions via estrogen receptor beta (ERbeta), the expression of this ER isoform was determined in bovine placentomes obtained from cows at midgestation (days 110-150; n=7), late gestation (days 180-280; n=9), from prepartal cows (sampling immediately after the prepartal decline in maternal progesterone blood levels became obvious; n=3) and from cows at normal term (n=5) on the protein and mRNA level. By means of immunohistochemistry using a monoclonal antibody against human ERbeta (clone PPG5/10), nuclear signals were found in numerous cell types of the fetal (cotyledon) and maternal (caruncle) component of the placentomes with highest intensities in mature trophoblast giant cells (TGC), fetal and maternal vascular cells and caruncular stromal cells, in which the percentage of positive cells increased from 58.9+/-2.3 and 59.1+/-3.3 at mid- and late gestation to 65.1+/-4.9 and 69.4+/-4.2 in prepartal and parturient cows, resp. (p<0.0001). Clear staining of uninucleated trophoblast cells was only observed in prepartal and parturient animals. Conventional RT-PCR confirmed ERbeta expression in caruncles and cotyledons at all phases under investigation. With semi-quantitative real-time RT-PCR higher levels of ERbeta-specific mRNA were measured in cotyledons compared to caruncles (p<0.01). The results show that in contrast to ERalpha, which is only expressed in the caruncle, ERbeta is also extensively expressed in the cotyledon and suggest a role of ERbeta primarily in TGC differentiation and placental angiogenesis and/or vascular functions.

Animals↗

Rapid improvement of recalcitrant disseminated granuloma annulare upon treatment with the tumour necrosis factor-alpha inhibitor, infliximab.

Granuloma annulare (GA) is a chronic inflammatory disorder of unknown aetiology, which is characterized clinically by erythematous plaques preferentially localized to the distal extremities, although disseminated variants exist. In light of the chronic relapsing nature of GA and lack of satisfactory treatment options, we initiated treatment with infliximab in a patient with chronic disseminated GA that was recalcitrant to standard treatment. The 59-year-old female patient with insulin-dependent diabetes had experienced GA lesions for more than 4 years despite various systemic and topical treatments. Systemic glucocorticoids were not a therapeutic option because of the preexisting unstable insulin-dependent diabetes. Infliximab was administered intravenously at 5 mg kg(-1) day(-1) at weeks 0, 2 and 6 and thereafter at a monthly interval for an additional 4 months. Most of the GA plaques resolved within 4-6 weeks, leaving postinflammatory brownish macules. Newly arising plaques disappeared within 2 weeks and new GA lesions were not observed during the entire observation period of more than 16 months. Infliximab may be an additional option in the treatment of recalcitrant forms of GA as well as in other chronic granulomatous skin disorders, such as sarcoidosis and necrobiosis lipoidica.

Antibodies, Monoclonal↗

Expression of oestrogen receptors alpha and beta and of aromatase in the testis of immature and mature boars.

The boar testis secretes high amounts of oestrogens. In order to test for a likely local significance, we investigated the expression of oestrogen receptors (ER) in immature and mature boar testes using immunohistochemistry (IHC), in vitro and in situ reverse transcription-polymerase chain reaction (RT-PCR). Samples were from 25 boars castrated at ages of 50, 100, 150, 200 and 250 days. Mouse monoclonal primary antibodies against porcine ERalpha (clone HT227), human ERbeta1 (clone PPG5/10) and human P450 aromatase (clone SM1671P) were used. Expression of the mRNA was tested utilizing primers specific for the respective porcine mRNA sequences. ER immunoreactivity was exclusively localized to the nuclei. In immature boars, 90.6 +/- 1.2% of prespermatogonia and 71.0 +/- 2.6% of the Leydig cells showed a strong staining for ERalpha; 95.5 +/- 3.5% of the prespermatogonia but none of the Leydig and Sertoli cells were ERbeta-positive. In mature boars a strong staining for the ERbeta was observed in virtually all Sertoli, Leydig and germ cells, except for the elongating/ed spermatids, which were clearly negative; for the ERalpha, strong immunoreaction signals were restricted to spermatogonia and primary spermatocytes with 93.6 +/- 2.7% of these cells being positive; distinctly less intensive signals were observed in 51.4 +/- 0.27% of the secondary spermatocytes, round spermatids and Leydig cells. In vitro RT-PCR was positive for both receptors and results of in situ RT-PCR matched those obtained by IHC. P450 aromatase immunoreaction was restricted to the cytoplasm of Leydig cells. These findings suggest that testicular ER may be important factors contributing to onset and maintenance of spermatogenesis in the boar.

Aging↗

[Therapeutic options in patients with diabetes mellitus type 2 and coronary artery disease: intensified secondary prevention versus percutaneous or surgical revascularization].

Diabetes mellitus is a major risk factor for coronary artery disease and is associated with accelerated disease progression and adverse prognosis. Although relief of symptoms can quickly be obtained by percutaneous intervention or bypass surgery, it does not change patients' prognoses, with the exception of stenoses of the left main stem or left anterior descending artery. A multifactorial intervention, which consists of a low-fat diet, glucose and arterial blood pressure control, smoking cessation and regular physical exercise, emerges as an alternative strategy since it leads to improvement of the modifiable risk factors, exercise tolerance and quality of life.

Angioplasty, Balloon, Coronary↗

[Primary prevention: physical activity].

Traditional risk factors such as smoking, hypertension and being overweight have received considerable attention in recent years, whereas physical activity as a preventive strategy does not enjoy the same public attention. In recent years the level of physical activity has decreased dramatically in children and adolescents in favor of time spent on the internet and in front of the TV. If this trend is allowed to develop along the same direction, a sharp increase in cardiovascular disease can be anticipated. The protective action of physical activity on the cardiovascular system has been well documented in large numbers of patients, and the basic physiological mechanisms have been elucidated. Metabolic changes comprise loss of weight, reduction in triglyceride and LDL levels, as well as an increase in HDL. Insulin sensitivity is enhanced in all tissues postponing the manifestation of diabetes mellitus. Shear forces created by physical activity induce ecNOS within the endothelial lining of the arteries. This enzyme is responsible for controlling vasomotion through the elaboration of NO which causes vasodilation in the smooth muscle within the vessel wall. Utilization of preformed collateral vessels has been postulated repeatedly; so far, however, it only could be documented in animals, not in humans. Nearly all studies concerned with primary prevention have shown a significant negative correlation between energy expenditure during exercise and cardiovascular mortality, even light and moderate exercise will result in a lower incidence. In order to eliminate a sedentary life style in children and adolescents, adequate programs should be initiated in all schools; they should aim for 60 min of physical activity on a daily basis.

Cholesterol, LDL↗

Endoluminal stent-graft placement for acute rupture of the descending thoracic aorta.

AIMS: To investigate the results of endovascular stent-graft placement for the treatment of acute perforating lesions of the descending thoracic aorta. METHODS AND RESULTS: A total of 31 consecutive patients underwent interventional treatment for perforating lesions of the descending aorta. In 21 cases (group A), the aortic perforation was due to rupture of a descending thoracic aneurysm or dissection, whereas 10 patients (group B) were treated for traumatic transection of the descending aorta. A total of 42 endoprostheses were implanted. The implantation procedure was successful in all cases without peri-interventional complications. In one case, implantation of a second endoprosthesis became necessary due to type I endoleak. Overall, the 30-day mortality was 9.7%. As all three deaths occurred in group A, the mortality rate in this group was 14.3% versus 0% in group B. Similarly, postinterventional complications were more prevalent, with 28.6% in group A (renal failure n = 4; stroke n = 2) versus 10.0% in group B (renal failure n = 1). No paraplegia and no further deaths or ruptures occurred during follow-up (mean 17 months). CONCLUSION: Interventional stent-graft placement is an effective treatment option for the emergency repair of descending aortic perforations.

Acute Kidney Injury↗

Melanoma or not? Cancer testis antigens may help.

BACKGROUND: Cancer testis antigens (CTAs) are expressed in a variety of malignant tumours. No CTA expression is found in normal adult tissues, except in male germ cells and occasionally placenta. To date, more than 20 CTAs or antigen families have been identified. OBJECTIVES: Owing to their tumour-associated expression pattern, CTAs may be useful for making a distinction between benign and malignant neoplasms. The present study was done to analyse the value of CTAs for the discrimination of cutaneous melanoma and naevi. PATIENTS AND METHODS: Primary melanomas (38) and 19 naevi were analysed for their expression of CTAs by immunohistochemistry using the following monoclonal antibodies (mAb) to the following antigens (mAb/antigen): MA454/MAGE-A1, 57B/MAGE-A4, ES121/NY-ESO-1. In a subset of melanomas (n = 26), the CTA panel was extended to three additional CTAs (mAb/antigen): CT7-33/MAGE-C1, M3H67/MAGE-A3 and GAGE/GAGE. RESULTS: All 19 naevi were negative for the mAbs MA454, M3H67, 57B, ES121, CT7-33 and GAGE. In melanoma, the immunoreactivity was as follows: MA454: 8/38 (21%), 57B 11/38 (29%), ES121 9/38 (24%). However, 19/38 (50%) were positive for at least one CTA. When 26 melanomas were tested for the expression of six different CTAs 20/26 (77%) were positive for at least one CTA. CONCLUSIONS: CTAs may be useful in the determination of suspected malignancy in cutaneous melanomas. The low incidence of particular CTAs can be overcome by increasing the number of CTAs analysed.

Antibodies, Monoclonal↗

Vaccines for birch pollen allergy based on genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1.

BACKGROUND: We have recently engineered recombinant derivatives of the major birch pollen allergen Bet v 1 (rBet v 1 fragments and trimer) with strongly reduced allergenic activity. OBJECTIVE: The aim of this study was the in vivo characterization of potential allergy vaccines based on Al(OH)3-adsorbed genetically modified rBet v 1 derivatives in mice. METHODS: BALB/c mice were immunized either with courses of nine injections of increasing doses of Al(OH)3-adsorbed rBet v 1 wild-type, rBet v 1 fragments, rBet v 1 trimer or Al(OH)3 alone in weekly intervals or with three high-dose injections applied in intervals of 3 weeks. Humoral immune responses to rBet v 1 wild-type and homologous plant allergens were measured by ELISA and Western blotting, and the ability of mouse antibodies to inhibit the binding of allergic patients IgE to Bet v 1 was studied by ELISA competition experiments. RESULTS: In both schemes, hypoallergenic rBet v 1 derivatives induced low IgE but high IgG1 responses against rBet v 1 wild-type. The IgG1 antibodies induced by genetically modified rBet v 1 derivatives cross-reacted with natural Bet v 1 and its homologues from alder (Aln g 1) as well as hazel (Cor a 1) and strongly inhibited the binding of birch pollen allergic patients' IgE to Bet v 1 wild-type. CONCLUSION: Genetically modified hypoallergenic rBet v 1 derivatives induce blocking antibodies in vivo. Their safety and efficacy for the treatment of birch pollen and associated plant allergies can now be evaluated in clinical immunotherapy studies.

Allergens↗