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P Helmbold

Publications and source records attributed to P Helmbold.

At least 19 recordsLinked to original sources
PubMed2007

[Primary nasal natural killer/T-cell lymphomas: classification and clinicopathological features].

BACKGROUND: Nasal NK/T-cell lymphomas are rare malignancies in Europe or North America. Histological diagnosis is difficult, because tumors imbedded in large necrotic areas and neoplastic infiltrates may be admixed with small lymphocytes, plasma cells, eosinophils, and histiocytes, and thus the process could be misdiagnosed as chronic inflammation. Progression of the disease leads to septal perforation and may also result in destruction of the hard palate, and if left untreated it ends fatally. This introduced the term "lethal midline granuloma", a term which should not be used any more. MATERIAL AND METHODS: Clinical features, pathohistology, and current classification of primary nasal NK/T-cell lymphomas are described against the background of the recent literature and a case report. RESULTS: Immunophenotyping is essential for the diagnosis. Tumor cells are uniformly infected by Epstein-Barr virus, which could be verified by EBER in situ hybridization. Immunohistochemically, tumor cells are positive for CD56, cytoplasmic CD3epsilon, and CD2 and they express cytotoxic molecules like granzyme B, TIA-1, GMP17, and perforin. Therapeutic options are radio- or radiochemotherapy. On average, 2- and 5-year survival rates of 50% are obtained in stages I and II. The prognosis of advanced tumor stages is very poor. CONCLUSIONS: Immunohistochemical and molecular genetic early diagnosis is of crucial prognostic relevance.

Adolescent↗
PubMed2006

Concomitant traumas influence prognosis in melanomas of the nail apparatus.

BACKGROUND: In nail apparatus melanomas (NAM), the role of standard melanoma prognostic factors is under discussion. The prognostic influence of traumas to the clinically apparent tumour has not been sufficiently examined. OBJECTIVES: To estimate the influence of traumas against the background of standard prognostic factors on the course of NAM. METHODS: In 33 patients (20 women, 13 men, median age 65.0 years) with NAM (median tumour thickness 3.5 mm), we retrospectively examined a detailed history of trauma to the affected extremity at first presentation. Histological or other standard prognostic factors and follow-up were studied prospectively using a standardized protocol. RESULTS: Of 33 patients, 21 had suffered injury to the clinically apparent melanoma primary between 4 and 72 months prior to definitive surgical treatment (diagnostic biopsy up to 3 months ahead of excision of the melanoma was not considered). Eight of these patients had undergone inadequate therapy procedures. In Kaplan-Meier analysis, trauma to the clinically apparent tumour and tumour thickness were found to be significant prognostic factors for recurrence-free survival, and trauma to the clinically apparent tumour, Clark level and tumour thickness were significant prognosis predictors for overall survival. In Cox's proportional hazards model, trauma to the clinically apparent tumour was found to be a significant and independent risk factor with regard to overall survival (hazard ratio 5.39; P = 0.029). An influence of trauma on the primary pathogenesis of NAM could not be confirmed. Only three patients reported trauma prior to the onset of tumour. CONCLUSIONS: From our data, trauma to the clinically apparent tumour might be a considerable risk factor in NAM. The diagnosis of NAM should be considered in lesions of the nail apparatus and further deterioration of the prognosis due to inadequate therapeutic attempts or injury to the NAM should be avoided.

Aged↗
PubMed2006

Epigenetic silencing contributes to frequent loss of the fragile histidine triad tumour suppressor in basal cell carcinomas.

BACKGROUND: Extensive exposure to ultraviolet radiation is associated with genetic alterations in basal cell carcinomas (BCCs), which represent some 75% of skin cancers. OBJECTIVES: As recent data suggested the fragile histidine triad (FHIT) gene product to participate in DNA damage responses we wished to address whether functional deletion of this tumour suppressor participates in the development of BCC. Our study focused on epigenetic inactivation of the FHIT gene. METHODS: Paraffin-embedded specimens from 17 patients with BCC were available for methylation-specific polymerase chain reaction (MSP), combined bisulphite-dependent restriction analysis (COBRA) of the FHIT gene and immunohistochemistry of its product. RESULTS: We report for the first time that 100% of BCCs are negative for FHIT by immunostaining. Aberrant methylation of the FHIT promoter occurred in a significant portion of BCCs. MSP detected hypermethylation of the FHIT/FRA3B locus in nine of nine (100%) periocular BCCs and in six of eight (75%) BCCs from other body regions. COBRA yielded similar results, confirming that some 88% of the 17 BCCs analysed harbour epigenetic silencing of the FHIT gene. Loss of FHIT protein was demonstrated immunohistochemically, confirming that promoter hypermethylation correlated with loss of gene expression. CONCLUSIONS: We have identified epigenetic silencing of the FHIT tumour suppressor gene as a frequent inactivation mechanism which is likely to contribute to functional deficiencies in DNA damage response of BCCs.

Acid Anhydride Hydrolases↗
PubMed2005

[Angioedema in hereditary deficiency of complement factor 1 esterase inhibitor and alpha 1-antitrypsin].

HISTORY AND CLINICAL FINDINGS: A 15-year-old girl had suffered from episodic, sometimes threatening angioedema of the face, nasopharyngeal space and distal extremities beginning at age 13. EXAMINATIONS: A C1-esterase inhibitor (C1-INH) deficiency was revealed protein-chemically and functionally. There was also an alpha (1)-antitrypsin (AAT) deficiency with heterocygotic phenotype PiMZ. The combination of C1-INH and AAT deficiency was also found in the patient's mother and brother. THERAPY AND COURSE: Under 8-month therapy with 200 mg/d danazol per os (reduction of the dosis in the last month to 100 mg/d), there was no further edema, the C1-INH concentration normalized and there was also an increase in C1-INH function. During the observation period, use of the emergency set with C1-INH concentrate was not required. CONCLUSIONS: This is the first reported case of angioedema in combination of two hereditary enzyme defects C1-INH deficiency (autosomal-dominant genetics) and AAT deficiency (autosomal-recessive). In addition to a survey of current literature, the current state of diagnostics and therapy of the hereditary angioedema is presented.

Administration, Oral↗
PubMed2005

[Long-term locally-recurrent melanoma].

Malignant melanoma is a highly malignant skin tumor with a widely variable individual course. Currently, approximately 75% of German patients can be cured of malignant melanoma by early diagnosis and excision, while more than 20% die of distant metastases of the melanoma. In contrast, there are single cases of long-term locally recurrent melanomas with neither complete cure nor development of distant metastases. We report on a female patient with a nevus-associated melanoma who was treated in 1968 with X-ray radiation (Dermopan, 100 Gy) with curative intent. In the following 31 years, the patient developed four phases of in-transit and satellite metastases in a zosteriform pattern as well as ilioinguinal lymph node metastasis. Since 1999, the patient has been free of recurrence. Besides the unusual biological features of this case, this report reflects the changes of paradigms in the therapy of melanoma over the last forty years.

Female↗
PubMed2002

[Merkel cell carcinoma].

Merkel cell carcinoma (cutaneous neuroendocrine carcinoma) is an uncommon, highly malignant, neuroendocrine skin tumour. Typically, the primary is a fast-growing tough dermal nodule that is characterized histologically by uniform round cells with a small cytoplasmic rim. The tumour cells express the cytokeratins 8, 18, 19, 20, neurofilament, synaptophysin, chromogranin, and neuron-specific enolase. A high frequency of local recurrences (25-77%) and lymph-node metastases (50%) are characteristic features of Merkel cell carcinoma. The 5-year survival rate is 30-74%. Merkel cell carcinomas are highly radiosensitive. Thus, besides surgical methods, radiation should be included into the treatment concept in every stage. We present four cases of Merkel cell carcinoma with different courses for a review-like discussion of this disease giving instructions for rapid diagnosis and effective therapy.

Aged↗
PubMed2002

[Long-term results of adjuvant chemotherapy after therapeutic lymph node dissection in patients with cutaneous malignant melanoma].

BACKGROUND AND OBJECTIVE: 224 patients with malignant melanoma and palpable axillary or inguinal lymphadenopathy underwent therapeutic lymph node dissection at the Martin-Luther-University in Halle, Germany. between 1983 and 1994. 120 received adjuvant chemotherapy; we evaluated the effects of various regimens in this group. PATIENTS/METHODS: Surgical treatment alone was performed in 104 patients. This group's results were compared to those of 94 patients who additionally received an adjuvant polychemotherapy [dacarbazine (DTIC), vincristine, 5-fluorouracil and hydroxyurea] and 26 patients who received either DTIC monotherapy or DTIC plus interferon-alfa. RESULTS: The median follow-up was 88 months. The 5-year survival rates were 31.0+/-5% after surgery alone, 26.4+/-4% after adjuvant polychemotherapy and 27.0+/-9% after DTIC based chemotherapy. The three survival curves did not differ significantly. In a multifactorial analysis, the number of metastatic lymph nodes was the single significant predictor of survival after therapeutic lymph node dissection, whereas Breslow thickness, ulceration, site of the primary melanoma, age, sex and adjuvant therapy were not significant. CONCLUSION: No beneficial effect of adjuvant chemotherapies could be demonstrated.

Adult↗
PubMed2001

Isolation and in vitro characterization of human dermal microvascular pericytes.

Pericytes cover the abluminal surface of capillaries and venules and are thought to play an important role in microvascular regulation and pathology. The purpose of this study was to isolate and characterize human dermal microvascular pericytes (HDMPC), a minor cell type in the skin but a relatively easily obtainable human source of tissue. We developed and compared two procedures that differed in the preselection method. Isolation of dermal microvessel fragments from neonatal foreskins by trypsin digestion was followed by mechanical release of subepidermal tissue, collagenase treatment, and sieving through 100- and 30-microm meshes. After subcultivation, pericytes were preselected either by isolation of outgrowing capillary fragments or by 3G5-coupled magnetic beads. Pericytes were selected finally by cultivation of single cells in endothelial cell-conditioned media. Cultured HDMPC were seen to be large and well spread with irregular edges and prominent stress fibers. They lack contact inhibition, are positive for 3G5 antigen, alpha-smooth muscle actin, and vimentin, and are negative for the endothelial cell marker CD31, diI-acetylated low-density lipoprotein uptake, cytokeratin 5, 6, and 18, and S100 protein. Using both preselection methods, we could establish purified cell cultures of HDMPC. The results of these studies represent the first report of HDMPC isolation.

Cell Separation↗
PubMed2001

[Merkel cell carcinoma: a diagnostic and therapeutic challenge].

Merkel cell carcinoma (cutaneous neuroendocrine carcinoma) is a highly malignant, neuroendocrine skin tumor. It mostly occurs in elderly patients in the sun-exposed skin of the head and neck and the extremities. Merkel cell carcinomas develop as fast-growing dermal tumors. They are characterized by a high frequency of lymph-node metastases (50%) and local recurrences (25-77%). The 5-year survival rate is 30-74%. Histology reveals uniform, round cells with a small cytoplasmic rim expressing cytokeratin 20, neurofilament, synaptophysin, chromogranin, and neuron-specific enolase. Ultrastructurally, 100-200 nm electron dense granules are typical findings. Wide surgical excision, followed by radiotherapy, is the treatment of choice. Regional lymph-node metastases should be treated by radical lymph-node excision and radiotherapy. In advanced metastatic Merkel cell carcinoma, a remission can be achieved by different chemotherapy schedules or the somatostatin analogue octreotide. However, the prognosis remains poor. The current knowledge about this disease and guidelines for effective diagnosis and treatment are given.

Biomarkers, Tumor↗
PubMed2001

[Recurrent chancriform mucous membrane ulcer in plasmacytoma with secondary IgA deficiency. Pyoderma chancriforme of the tongue].

A 66 year old patient presented with a nine month history of recurrent oral ulcerations involving the tongue. We diagnosed chancriform pyoderma and a previously not identified multiple myeloma with secondary immunoglobulin deficiency. Clinically and histologically we excluded a necrotizing ulcerative stomatitis as found in individuals with cellular immunodeficiency as in late-stage HIV-infection. On culture only Neisseria catarrhalis was found. Chancriform pyoderma is often associated with local bacterial infections, especially Staphylococcus aureus. The most common sites are the genitalia and periorbital region; involvement of the oral mucosa is uncommon. To the best of our knowledge, this is the fourth reported case with tongue lesions. The multiple myeloma-associated immunoglobulin deficiency might have facilitated the oral manifestations of chancriform pyoderma.

Aged↗
PubMed2001

Human dermal pericytes express 3G5 ganglioside--a new approach for microvessel histology in the skin.

BACKGROUND: Pericytes cover the abluminal surface of microvessels and play an important role in capillary regulation and pathology. Studies on pericytes have been hindered by the lack of specific markers with which to facilitate microscopic identification of this cell type. Expression of the cell surface 3G5 ganglioside antigen has been reported in cultured retinal and cardiac pericytes. The objective of this study was to determine the usefulness of monoclonal antibody 3G5 as a pericyte marker in human skin. METHODS: Cryosections of 21 skin biopsies were examined by direct fluorescence technique with anti-3G5, anti-von Willebrand factor, anti-alpha-smooth muscle actin or DNA fluorochrome. RESULTS: In human dermis, 3G5 expression is limited to pericytes discriminating this cell type from all other cells including smooth muscle cells, myofibroblasts and myoepithelial cells. We found a pericyte: endothelial cell ratio of 1:12.4 (+/-7.1), and a difference of alpha-smooth muscle actin expression between the subpapillary plexus and the microvessels of the Stratum reticulare. CONCLUSIONS: 3G5 mAB is an excellent and so far the only reported tool for identification of dermal pericytes by fluorescent light microscopy. Moreover, this is the first report of the application of 3G5 technique to the microvasculature in tissue sections at the light microscopic level.

Adolescent↗
PubMed2001

The NO release test as a functional reference standard for laser Doppler fluxmetry in cutaneous microangiology.

BACKGROUND/AIMS: The application of one-dimensional laser Doppler fluxmetry (LDF) to clinical research is widespread. Large intra- and interindividual fluctuations in perfusion impede the objective evaluation of studies and hinder a standardised reproducibility. Attempts are made to minimise these biological fluctuations of the measured values by means of functional tests, standardised measuring conditions and large study populations. An intraindividual fixed standard that also facilitates interindividual comparability as a reference parameter would be desirable. METHODS: By applying a nitric oxide (NO) release cream, a maximal vasodilatation is produced in a circumscribed skin area and optically registered by means of LDF. An LDF quotient is defined as a measure of the reproducibility. A total of 123 test subjects with dermatological diseases were measured at intervals of 60 min on the volar underarm on clinically normal skin with and without NO release cream. RESULTS: The LDF quotient of the NO release test represents a stable, readily reproducible individual parameter and is appropriate as a reference standard for resting flux measurements. Therefore, we define an LDF factor that includes the maximal vasodilatation as a specific assessment characteristic and thus allows a more powerful, functionally oriented assessment of the individual measurements. CONCLUSION: The NO release test is appropriate as a reference standard for laser Doppler fluxmetry and realises a high reproducibility of individual measurements.

Humans↗
PubMed1999

[Congenital melanocytic nevi].

Congenital melanocytic nevi are benign skin tumours with a population-based prevalence of 1-6%. They run an increased life-time risk of transformation into malignant melanoma. Additionally, they can be associated with an involvement of the leptomeninges (neurocutaneous melanosis), and may cause considerable cosmetic and psychic problems. In contrast to the past, the risk of congenital melanocytic nevi developing into melanoma is now regarded as well-established. Thus, excision is recommended whenever possible. Large lesions which do not allow complete excision should be treated by dermabrasion within the first weeks of life.

Adolescent↗
PubMed1998

Low-dose oral etoposide monotherapy in adult Langerhans cell histiocytosis.

BACKGROUND: The purpose of this study was to test the disease-controlling effect of low-dose oral etoposide monotherapy in adult-onset multisystem Langerhans cell histiocytosis. There are no previous reports of low-dose etoposide monotherapy for this condition. OBSERVATIONS: A 27-year-old man with a 7-year history of multifocal chronic Langerhans cell histiocytosis presented with severe disabling ulcers in intertriginous areas. He had previously been treated with 2 different regimens of antitumoral chemotherapy; one had to be discontinued due to myelosuppression and the other had proved ineffective. We treated with oral etoposide monotherapy at 50 mg/d (22 mg/m2 per day) for 21 days. The treatment was repeated at 28-day intervals for a total of 6 cycles. A rapid initial response with subtotal diminution of the involved skin area was found. No adverse effects were observed. The clinical picture has remained stable during the 7 months following cessation of therapy. CONCLUSION: Low-dose oral etoposide treatment is an adequate therapeutic measure for prolonged disease control in adult-type Langerhans cell histiocytosis.

Administration, Oral↗
PubMed1993

Induction of type IV hypersensitivity to contact allergens in guinea pigs by in vitro haptenized allogenic peritoneal exudate cells.

The induction of type IV hypersensitivity to contact allergens in guinea pigs has been studied by using allogenic peritoneal exudate cells (> 90% macrophages), which had been incubated primarily in vitro with dinitrochlorobenzene, formaldehyde, potassium dichromate, nickel II sulphate or para-aminobenzoic acid. In these guinea pig sensitization experiments Freund's complete adjuvant was used. In all haptens investigated the sensitization rates of the presented method were parallel to the known contact allergenicity in humans and, apart from the potassium dichromate results, comparable with those of the guinea pig maximization test. Because of its alternative immunization procedure, in which only few or no allergen molecules escape the effective presentation pathway, the authors conclude that this method could be developed into a predictive test assay for the evaluation of the contact allergenicity of water-soluble substances.

Allergens↗