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1.
Br J Dermatol ; 178(2): 443-451, 2018 02.
Article in English | MEDLINE | ID: mdl-28707317

ABSTRACT

BACKGROUND: Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous melanoma (CM). Although ALM has a poorer prognosis than other CM subtypes, the prognostic factors associated with ALM have only been verified in small-sized cohorts because of the low incidence of ALM worldwide. OBJECTIVES: To investigate the clinical characteristics of ALM and to evaluate their prognostic values based on a large dataset from the Central Malignant Melanoma Registry (CMMR) of the German Dermatologic Society. METHODS: The Kaplan-Meier method was used to estimate the potential influence of clinical and histological parameters on ALM disease-specific survival (DSS) curves, which were compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors for DSS. RESULTS: In total, 2050 patients with ALM were identified from 58 949 patients with CM recorded by the CMMR with follow-up data. In multivariate analyses, age (P = 0·006), ulceration (P = 0·013), tumour thickness (P < 0·001) and tumour spread (P < 0·001) turned out to be significant prognostic factors for DSS in ALM whereas sex, nevus association and level of invasion were not independent factors. CONCLUSIONS: ALM has the same prognostic factors as other subtypes of melanoma. Unfavourable prognosis probably derives from the delay in diagnosis in comparison with other melanoma subtypes.


Subject(s)
Hutchinson's Melanotic Freckle/mortality , Melanoma/mortality , Skin Neoplasms/mortality , Adult , Aged , Austria/epidemiology , Female , Foot Diseases/mortality , Germany/epidemiology , Hand , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Registries , Switzerland/epidemiology , Melanoma, Cutaneous Malignant
2.
Clin Genet ; 91(2): 339-343, 2017 02.
Article in English | MEDLINE | ID: mdl-27452416

ABSTRACT

Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and genitopatellar syndrome (GTPTS) are clinically similar disorders with some overlapping features. Although they are currently considered to be distinct clinical entities, both were found to be caused by de novo truncating sequence variants in the KAT6B (lysine acetyltransferase 6B) gene, strongly suggesting that they are allelic disorders. Herein, we report the clinical and genetic findings in a girl presenting with a serious multiple congenital anomaly syndrome with phenotypic features overlapping both SBBYSS and GTPTS; pointing out that the clinical distinction between these disorders is not exact and there do exist patients, in whom conventional clinical classification is problematic. Genetic analyses revealed a truncating c.4592delA (p.Asn1531Thrfs*18) variant in the last KAT6B exon. Our findings support that phenotypes associated with typical KAT6B disease-causing variants should be referred to as 'KAT6B spectrum disorders' or 'KAT6B related disorders', rather than their current SBBYSS and GTPTS classification.


Subject(s)
Abnormalities, Multiple/diagnosis , Blepharophimosis/diagnosis , Congenital Hypothyroidism/diagnosis , Craniofacial Abnormalities/diagnosis , Heart Defects, Congenital/diagnosis , Histone Acetyltransferases/genetics , Intellectual Disability/diagnosis , Joint Instability/diagnosis , Kidney/abnormalities , Patella/abnormalities , Psychomotor Disorders/diagnosis , Scrotum/abnormalities , Urogenital Abnormalities/diagnosis , Abnormalities, Multiple/genetics , Abnormalities, Multiple/pathology , Blepharophimosis/genetics , Blepharophimosis/pathology , Child, Preschool , Congenital Hypothyroidism/genetics , Congenital Hypothyroidism/pathology , Craniofacial Abnormalities/genetics , Craniofacial Abnormalities/pathology , Exons , Facies , Female , Heart Defects, Congenital/genetics , Heart Defects, Congenital/pathology , Humans , Intellectual Disability/genetics , Intellectual Disability/pathology , Joint Instability/genetics , Joint Instability/pathology , Kidney/pathology , Mutation , Patella/pathology , Phenotype , Psychomotor Disorders/genetics , Psychomotor Disorders/pathology , Scrotum/pathology , Urogenital Abnormalities/genetics , Urogenital Abnormalities/pathology
3.
Article in English | MEDLINE | ID: mdl-25569990

ABSTRACT

In neuroscience optogenetics was established as common research method. However, the devices used for opto-genetical stimulation, so called optrodes, are often made of stiff materials which lead to cell damage. We investigated the suitability of the epoxy based polymers SU-8, EpoClad and EpoCore for the fabrication of bendable thin-film waveguides. With the integration of such waveguides into neural electrodes flexible optrodes could be realized which would allow simultaneous stimulation at different sites. Three different waveguide types were fabricated with SU-8 and EpoClad as cladding and EpoCore as core materials. The optical losses were measured from 12.9 dB (SU-8 and air cladding) over 14.4 dB (SU-8 cladding) to 22.4 dB (EpoClad cladding). Aging in air at 23 °C for a time period of 80 days led to a continuous increase of the losses, which seemed to adapt to an upper limit of over 20 dB. Samples aged in saline solution at 37 °C showed a faster increase in the first 20 days, but a similar upper limit.


Subject(s)
Brain/physiology , Electrodes, Implanted , Epoxy Compounds/chemistry , Optical Phenomena , Polymers/chemistry , Time Factors
7.
Endoscopy ; 43(6): 490-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21618149

ABSTRACT

BACKGROUND AND STUDY AIM: The aim of this study was to develop an algorithm to detect small-bowel metastasis (SBM) of melanoma by sequential laboratory parameters and pan-intestinal endoscopy (PIE) including video capsule endoscopy (VCE). PATIENTS AND METHODS: A total of 390 melanoma patients (AJCC stage I/II/III/IV, 140/80/121/49) were screened for signs of intestinal blood loss (fecal occult blood test [FOBT] or overt bleeding) in an open, multicenter, prospective study, and those who were positive underwent PIE. Independent of the presence of intestinal bleeding, all stage IV patients were offered PIE. Follow-up was obtained in 357 patients (91.5 %) for a median of 16 months. We undertook to identify possible associations between SBM and clinical and laboratory data. Survival data were analyzed with regard to clinical and laboratory data and small-bowel findings. RESULTS: Intestinal blood loss was suspected in 49 of 390 patients (12.6 %), 38 of whom (77.6 %) agreed to undergo endoscopy. In 10 patients, SBM was detected by VCE (intention-to-diagnose, 20.4 %; AJCC III, n = 2; AJCC IV, n = 8). The SBM was resected in five patients. Total detection rates of SBM were 14 of 49 patients in stage IV (28.6 %, intention-to-diagnose), 2 of 121 in stage III (1.7 %), and 0 in stage I/II. In FOBT-positive patients, SBM detection rates were 72.7 %, 14.3 %, and 0 % in tumor stages IV, III, and I/II, respectively. Positive FOBT proved to be an independent negative prognostic factor for total survival in stage III and IV melanoma. CONCLUSIONS: SBMs are frequent in advanced melanoma. In stage III patients, screening for intestinal blood loss by PIE may help to identify SBMs. In stage IV, indication for PIE should depend on the individual consequences of detecting SBM, but not on bleeding symptoms alone.


Subject(s)
Algorithms , Endoscopy, Gastrointestinal , Gastrointestinal Hemorrhage/etiology , Intestinal Neoplasms/secondary , Melanoma/secondary , Occult Blood , Skin Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Female , Humans , Intestinal Neoplasms/complications , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/surgery , Male , Melanoma/pathology , Middle Aged , Prospective Studies , Survival Rate , Young Adult
10.
Dtsch Med Wochenschr ; 134(21): 1106-9, 2009 May.
Article in German | MEDLINE | ID: mdl-19437374

ABSTRACT

HISTORY AND CLINICAL FINDINGS: A 46-year-old man presented with suberythrodermia and an acral-accentuated sclerosis, which had been progressing over the past 6 months, with extensive, painful ulcers within the sclerotic areas of the calf. Due to acute myelotic leukemia (AML), an allogenic peripheral blood stem-cell transplantation with subsequent immunosupression with mycophenolatmofetil (MMF) and ciclosporin A had been performed 8 years previously. The patient had discontinued treatment on his own after about 2 years, having suffered a cerebroischemic insult in the meantime. INVESTIGATIONS: Histological examinations revealed sclerodermatous changes. Titres of antinuclear antibodies were unremarkable. Laser-Doppler-flowmetry also indicated an active inflammatory and sclerosing process. FACS analysis of the peripheral blood did not reveal signs of AML recurrence. DIAGNOSIS, THERAPY AND COURSE: The histological pattern in conjunction with the anamnesis indicated a cutaneous chronic graft-versus-host disease (GvHD). No further organ involvement was observed. The MMF therapy which the patient had discontinued was restarted. In addition, PUVA therapy was initiated. These measures and intensive physiotherapeutic exercises in parallel prevented further progression of the sclerosis and secondary mobility limitations. The ulcers healed completely with pentoxifylline and anti-infective treatment. CONCLUSION: After stem-cell transplantation, early diagnosis of GvHD is especially important due to possible irreversible sclerodermatous changes and other organ manifestations. Also for this reason, strict clinical follow-up is especially important with respect to compliance and efficacy of the immunosuppression.


Subject(s)
Graft vs Host Disease/etiology , Leukemia, Myeloid, Acute/therapy , Peripheral Blood Stem Cell Transplantation/adverse effects , Scleroderma, Localized/etiology , Anti-Infective Agents/therapeutic use , Cyclosporine/therapeutic use , Graft vs Host Disease/diagnosis , Graft vs Host Disease/therapy , Humans , Immunosuppressive Agents/therapeutic use , Laser-Doppler Flowmetry , Leg Ulcer/diagnosis , Leg Ulcer/etiology , Leg Ulcer/therapy , Male , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , PUVA Therapy , Patient Compliance , Pentoxifylline/therapeutic use , Physical Therapy Modalities , Scleroderma, Localized/diagnosis , Scleroderma, Localized/therapy , Transplantation, Homologous , Vasodilator Agents/therapeutic use
11.
Hautarzt ; 60(11): 913-5, 2009 Nov.
Article in German | MEDLINE | ID: mdl-19387593

ABSTRACT

Symptomatic cardiac melanoma metastases are very rare. A 76-year-old woman was admitted because of dyspnea and intrathoracic pain 8 years after surgery of a superficial spreading melanoma and 4 years after resection of in-transit metastases. MRI and echocardiography disclosed an intracavitary right atrial mass. Histologically a cardiac melanoma metastasis was found. Unspecific cardiac symptoms in a patient with elevated risk for distant metastases of melanoma should be further investigated to discover cardiac metastasis early.


Subject(s)
Heart Neoplasms/diagnosis , Heart Neoplasms/secondary , Melanoma/diagnosis , Melanoma/secondary , Skin Neoplasms/diagnosis , Aged , Chest Pain/diagnosis , Chest Pain/etiology , Dyspnea/diagnosis , Dyspnea/etiology , Female , Heart Neoplasms/complications , Humans , Melanoma/complications , Skin Neoplasms/complications
12.
Clin Exp Allergy ; 39(1): 159-66, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19040466

ABSTRACT

BACKGROUND: Pollen-associated food allergy is common. However, systemic reactions or even life-threatening anaphylaxis are rare. OBJECTIVE: The aim of this study was to investigate the clinical impact of native, heat-processed and encapsulated hazelnuts (HN) in patients with proven HN allergy. METHODS: One hundred and thirty-two patients with a positive history of HN allergy were recruited. Sensitization was confirmed by a skin prick test (SPT) and sIgE against HN. After an HN-free diet, double-blind placebo-controlled challenges were performed with increasing amounts of native and roasted HN. A subset of patients were given HN capsules to circumvent the oral mucosa. Basophil activation was measured by flow cytometry before and after provocation but also ex vivo using native and roasted HN extracts. RESULTS: Three groups of HN-allergic patients were identified depending on their clinical reaction pattern. The dosages by which allergic reactions were elicitated varied for native HN from 0.01 to 2.0 g, with a median of 0.1 g, for roasted HN from 0.01 to 10.0 g, with a median of 0.23 g, and for encapsulated HN from 0.1 to 3.0 g, with a median of 0.3 g. Accordingly, the SPT was more frequently positive and resulted in greater weal reactions if native HN was used. This finding was confirmed by ex vivo basophil activation showing that significantly higher allergen extract concentrations (roasted>native) were necessary to induce 50% basophil activation. CONCLUSION: Our data show that heat processing of HN reduces its allergenicity. SPT but also the basophil activation test can be used to determine the reactivity of an allergen extract.


Subject(s)
Allergens , Capsules , Corylus , Hot Temperature , Nut Hypersensitivity/physiopathology , Plant Extracts , Adult , Aged , Allergens/adverse effects , Allergens/immunology , Basophils/immunology , Capsules/adverse effects , Corylus/adverse effects , Corylus/immunology , Double-Blind Method , Humans , Immunoglobulin E/blood , Middle Aged , Nut Hypersensitivity/immunology , Plant Extracts/adverse effects , Plant Extracts/immunology , Severity of Illness Index , Skin Tests , Young Adult
13.
Dtsch Med Wochenschr ; 133(27): 1429-32, 2008 Jul.
Article in German | MEDLINE | ID: mdl-18592451

ABSTRACT

HISTORY: A 57-year-old man was admitted with hemorrhagic papules and necrotising nodules on both elbows and upper legs. Recurrent arthralgia occurred. INVESTIGATIONS: The skin biopsy showed a cutaneous necrotising vasculitis. Positive test results for c-ANCA and proteinase 3 antibodies and a slightly increased WBC and a mild proteinuria were noticeable. DIAGNOSIS, TREATMENT AND COURSE: The diagnosis of an early systemic Wegener's granulomatosis was based on elevated proteinase 3-titres and cutaneous histologic findings as necrotising vasculitis and granulomatous inflammation. Treatment with prednisolone followed by methotrexate resolved the cutaneous symptoms and the arthralgia completely. Three months later the patient developed a progredient methotrexate toxicity caused by a glomerulonephritis. CONCLUSION: Wegener's granulomatosis should be considered if a cutaneous necrotising vasculitis is diagnosed. A cutaneous manifestation could be an early symptom. Methotrexate could be used for treatment of mild courses of Wegener's disease without renal involvement.


Subject(s)
Granulomatosis with Polyangiitis/diagnosis , Leg Dermatoses/diagnosis , Skin Diseases, Vascular/diagnosis , Antibodies, Antineutrophil Cytoplasmic/blood , Biopsy , Drug Therapy, Combination , Glomerulonephritis/chemically induced , Granulomatosis with Polyangiitis/immunology , Humans , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/toxicity , Leg Dermatoses/immunology , Leukocyte Count , Male , Methotrexate/therapeutic use , Methotrexate/toxicity , Middle Aged , Myeloblastin/immunology , Necrosis , Prednisolone/therapeutic use , Prednisolone/toxicity , Skin/pathology , Skin Diseases, Vascular/immunology
16.
Dtsch Med Wochenschr ; 132(49): 2624-6, 2007 Dec.
Article in German | MEDLINE | ID: mdl-18050026

ABSTRACT

HISTORY: A 60-year-old man with diabetes mellitus and chronic renal insufficiency needing hemodialysis was admitted with a 3 months history of multiple hyperkeratotic papules on the trunk and extremities partly ulcerated with a keratotic central plug. INVESTIGATIONS: Laboratory tests revealed elevated levels of blood urea nitrogen, creatinine, and HbA (1c). Histopathology showed vertical strands of collagen perforating from the ulcerated lesions. COURSE, DIAGNOSIS AND TREATMENT: The biopsy specimen was consistent with acquired reactive perforating collagenosis. The progression was stopped and secondary wound healing was initiated after two weeks of therapy with allopurinol and PUVA. CONCLUSION: Acquired reactive perforating collagenosis should be considered when ulcera with oystershell-like keratotic plugs are found especially in patients with predisposing diseases like diabetes and renal insufficiency. A good interdisciplinary cooperation between internist and dermatologist is crucial for the early recognition by histopathology and the immediate treatment.


Subject(s)
Collagen Diseases/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Kidney Failure, Chronic/epidemiology , Skin Diseases/epidemiology , Allopurinol/therapeutic use , Antimetabolites/therapeutic use , Blood Urea Nitrogen , Collagen Diseases/drug therapy , Collagen Diseases/pathology , Creatinine/blood , Diabetes Mellitus, Type 2/complications , Glycated Hemoglobin/analysis , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Middle Aged , PUVA Therapy , Skin/pathology , Skin Diseases/drug therapy , Skin Diseases/pathology , Skin Ulcer/drug therapy , Skin Ulcer/epidemiology , Skin Ulcer/pathology , Treatment Outcome
17.
Histol Histopathol ; 22(9): 1005-15, 2007 09.
Article in English | MEDLINE | ID: mdl-17523078

ABSTRACT

To investigate intra-tumoural coexistence and heterogeneity of aberrant promoter hypermethylation of different tumour suppressor genes in melanoma, we analyzed the intra-tumoural distribution of promoter methylation of RASSF1A, p16, DAPK, MGMT, and Rb in 339 assays of 34 tumours (15 melanoma primaries, 19 metastases) by methylation-specific PCR, correlation to histopathology and RASSF1A expression. We detected promoter hypermethylation of at least one gene in 74% of tumours (30%, 52%, 33%, 20%, and 40% for RASSF1A, p16, DAPK, MGMT and Rb, respectively). 70% of the cases exhibited an inhomogeneous methylation pattern (17%, 45%, 33%, 20%, and 40% for RASSF1A, p16, DAPK, MGMT and Rb, respectively). Samples from the core of the tumours represented the methylation state of the whole tumours more accurately than the periphery. Local intra-tumoural correlation was found between the promoter hypermethylation state of p16 and Rb or p16 and DAPK, or epitheloid tumour cell type and RASSF1A or p16 methylation. Mitosis rate and sex was correlated with methylation of RASSF1A. Histological results confirmed that promoter hypermethylation of RASSF1A led to aberrant expression patterns. We conclude that intra-tumoural inhomogeneity of promoter hypermethylation is frequent in melanoma and this supports the hypothesis of clonal instability during progression of melanomas. In prognosis studies, missing the intra-tumoural sample representativeness may result in a reduction of the sensitivities or specificities.


Subject(s)
DNA Methylation , Genes, p16 , Genetic Heterogeneity , Melanoma/genetics , Melanoma/metabolism , Promoter Regions, Genetic , Adult , Aged , Aged, 80 and over , Apoptosis Regulatory Proteins/genetics , Calcium-Calmodulin-Dependent Protein Kinases/genetics , DNA/genetics , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Death-Associated Protein Kinases , Female , Genes, Tumor Suppressor , Humans , Immunohistochemistry , Male , Melanoma/pathology , Middle Aged , Neoplasm Metastasis , Polymerase Chain Reaction , Retinoblastoma Protein/genetics , Tumor Suppressor Proteins/genetics
18.
Hautarzt ; 58(2): 142-5, 2007 Feb.
Article in German | MEDLINE | ID: mdl-16525742

ABSTRACT

High-dose steroids in combination with other immunosuppressant substances, usually azathioprine, are the therapy of choice in pemphigus vulgaris. Complete remission can be difficult to achieve, with mucosal lesions often recalcitrant. We describe two patients in whom gold in the form of sodium aurothiomalate was effective in resolving mucosal lesions. Initially both patients were treated with high-dose corticosteroids, one in combination with mycophenolate mofetil. Their oral lesions proved to be stubborn but responded well to intramuscular gold, which also showed a steroid-sparing effect, so that the dosage of corticosteroids could be reduced to a minimum. Sodium aurothiomalate was continued until both patients were in remission without any side effects.


Subject(s)
Antirheumatic Agents/therapeutic use , Gold Sodium Thiomalate/therapeutic use , Pemphigus/drug therapy , Stomatitis/drug therapy , Adult , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Resistance , Female , Humans , Injections, Intramuscular , Male , Middle Aged , Pemphigus/diagnosis , Stomatitis/diagnosis
19.
Cytogenet Genome Res ; 115(1): 23-9, 2006.
Article in English | MEDLINE | ID: mdl-16974080

ABSTRACT

Scapinin has been found to bind to cytoplasmic actin and is also a putative regulatory subunit of protein phosphatase-1 (PP1). It is found attached to the nuclear matrix-intermediate filament (NM-IF) and is down-regulated by differentiation of tumor cells. We have analyzed the genomic structure and tissue-specific expression pattern of both the human scapinin gene (PHACTR3) and the orthologous mouse gene. Both genes showed a highly conserved complex genomic organization with four different leader exons. Alternative splicing of exon 5 was found to be limited to human and variable polyadenylation in mouse transcripts only. In both species expression seems to occur predominantly in the brain. By Northern blot analysis two major transcripts in human and three transcripts in mouse were detected. Expression analysis in the mouse revealed a tissue-specific complex transcription pattern in the brain and a specific pattern was observed during prenatal development. Based on the transcriptional data we therefore assume scapinin to have a distinct biological function in the mammalian brain.


Subject(s)
Gene Components , Gene Expression Regulation , Nuclear Proteins/genetics , Alternative Splicing , Animals , Brain/metabolism , Exons , Fetal Development/genetics , Humans , Mice , RNA, Messenger/analysis , Species Specificity , Tissue Distribution
20.
Nuklearmedizin ; 45(2): 88-95, 2006.
Article in English | MEDLINE | ID: mdl-16547570

ABSTRACT

AIM: This study investigates whether interactive rigid fusion of routine PET and CT data improves localization, detection and characterization of lesions compared to separate reading. For this purpose, routine PET and CT scans of patients with metastases from malignant melanoma were used. PATIENTS, METHODS: In 34 patients with histologically confirmed malignant melanoma, FDG-PET and spiral CT were performed using clinical standard protocols. For all of these patients, gold standard was available. Clinical and radiological follow-up identified 82 lesions as definitely pathological. Two board-certified nuclear medicine physicians and two board-certified radiologists analyzed PET and CT images independently from each other. For each patient up to 32 anatomical regions (24 lymph node regions, 8 extranodular regions) were systematically classified. Discordant areas were interactively analyzed in manually and rigidly registered images using a commercially available fusion tool. No side-by-side reading was performed. RESULTS: Image fusion disclosed that the evaluation of the PET images alone led to a mislocalization in 26 of 91 focally FDG enhancing lesions. The overall sensitivities of PET, CT, and image fusion were 85, 88, and 94%, respectively; the overall specificities of PET, CT and image fusion were 98, 95 and 100%, respectively. Image fusion exhibited statistically significant higher specificity values as compared with CT. Ten definitely malignant sites were false-negative in CT, but could be detected by PET. On the other hand, twelve metastases were false-negative in PET, but could be detected by CT. These included two lesions, which had a clear correlate on the PET image when the fused images were evaluated. On the whole, registration of the PET and CT images yielded additional diagnostic information in 44% of the definitely malignant lesions. CONCLUSION: Retrospective image fusion of independently obtained PET and CT data is particularly valuable in exactly localizing foci of abnormal FDG uptake and improves the detection of metastases of malignant melanoma.


Subject(s)
Fluorodeoxyglucose F18 , Melanoma/diagnostic imaging , Positron-Emission Tomography/methods , Tomography, X-Ray Computed/methods , Adult , Aged , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Radiopharmaceuticals , Reproducibility of Results , Retrospective Studies
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