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Biomedical subjects

Peter Altmeyer

Publications and source records attributed to Peter Altmeyer.

At least 37 records · Page 2Linked to original sources

Modulation of endothelial dysfunction and apoptosis: UVA1-mediated skin improvement in systemic sclerosis.

UVA1-mediated effects regarding vascular dysregulation as a primary pathogenetic factor of systemic sclerosis skin lesions have so far not been investigated. Pre- and posttherapy skin biopsies of four patients were evaluated immunohistochemically for angiostatic, angiogenic and angioapoptotic features. Immunohistochemistry revealed a partial pretherapy loss of endothelial CD31 and CD34 expression accompanied by a posttherapy increase of CD34(+) cells. Simultaneously, VEGF and M30 CytoDEATH immunolabeling demonstrated UVA1-induced neovascularization and decreased endothelial apoptosis. Our results suggest that UVA1 irradiation exerts its positive effects by a modulation of endothelial regulation/transformation beside the proposed induction of T cell apoptosis and collagenases.

Antibodies, Monoclonal↗

Immunohistochemical investigations and introduction of new therapeutic strategies in scleromyxoedema: case report.

BACKGROUND: Scleromyxoedema is a rare chronic skin disease of obscure origin, which may often be associated with severe internal co-morbidity. Even though different casuistic treatment modalities have been described, to date, curing still seems to be impossible. CASE PRESENTATION: We report a 44-year-old Caucasian female presenting with remarkable circumscribed, erythematous to skin-coloured, indurated skin eruptions at the forehead, arms, shoulders, legs and the gluteal region. Routine histology and Alcian blue labelling confirmed a massive deposition of acid mucopolysaccharides. Immunohistochemical investigations revealed proliferating fibroblasts and a discrete lymphocytic infiltration as well as increased dermal expression of MIB-1+ and anti-mastcell-tryptase+ cells. Bone marrow biopsies confirmed a monoclonal gammopathy of undetermined significance without morphological characteristics of plasmocytoma; immunofixation unveiled the presence of IgG-kappa paraproteins. CONCLUSIONS: Taking all data into account, our patient exhibited a complex form of lichen mxyoedematosus, which could most likely be linked a variant of scleromyxoedema. Experimental treatment with methotrexate resulted in a stabilisation of clinical symptoms but no improvement after five months of therapy. A subsequent therapeutic attempt by the use of medium-dose ultraviolet A1 cold-light photomonotherapy led to a further stabilisation of clinical symptoms, but could not induce a sustained amelioration of skin condition.

Adult↗

UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review.

BACKGROUND: Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. METHODS: Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. RESULTS: Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. CONCLUSIONS: Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications.

Adult↗

UVA1-induced decrease in dermal neuron-specific enolase (NSE) in acrosclerosis.

Besides its role in small-cell carcinoma of the lung, elevated serum levels of neuron-specific enolase (NSE) have recently been reported to be associated with autoimmune rheumatic disorders such as systemic sclerosis. Serum NSE seems to correlate with disease activity as well as Rodnan skin score. The aim of the study was to assess the neuromodulatory effects of conventional UVA1 phototherapy on acrosclerosis as an additional mechanism besides an assumed T cell apoptosis, collagenase induction and angiogenesis. Punch skin biopsies of acrosclerotic skin lesions taken before and after treatment from four patients were evaluated immunohistochemically for the presence of NSE, S100 and neurofilament. Immunolabeling revealed a UVA-induced decrease in dermal NSE expression. In contrast, no alteration in neurofilament+ cells could be detected. In line with the findings of a previous investigation, a high number of S100+ cells were detected in most specimens. We demonstrated a UVA1-induced reduction in dermal NSE levels correlating with a softening of former sclerotic lesions. Even though the origin and the functional mechanisms remain obscure, NSE might be relevant directly within sclerotic skin lesions and may possibly be used as a diagnostic marker at least in SSc-associated acrosclerotic skin.

Humans↗

Low-dose UVA1 phototherapy in systemic sclerosis: effects on acrosclerosis.

BACKGROUND: Increased collagen synthesis, vascular damage, and T-lymphocytic infiltration contribute to the development of systemic sclerosis. Preliminary studies revealed the effectiveness of low-dose UVA1 phototherapy in acrosclerosis. OBJECTIVE: We sought to confirm data of a pilot study revealing the efficacy of low-dose UVA1 irradiation in acrosclerosis in a larger number of patients. METHODS: Symptoms of 18 patients receiving low-dose UVA1 phototherapy were evaluated clinically and biometrically in an open, nonrandomized study. A number of pretherapeutic and posttherapeutic biopsy specimens were tested immunohistochemically for matrix-metalloproteinase-1. RESULTS: UVA1 irradiation led to softening of former stiffness reflected by a significant decrease of the hand score, increase of total skin distension, and reduction of skin thickness. Posttherapeutically, matrix-metalloproteinase-1 immunolabeling revealed a significant dermal elevation of collagenase. CONCLUSION: Low-dose UVA1 phototherapy is a capable treatment option for acrosclerosis. Its beneficial effect may be mediated by the induction of collagenases and a reduction of collagen deposition and cellular infiltration.

Adult↗

Pimecrolimus 1% cream for cutaneous lupus erythematosus.

Topical treatment of cutaneous lupus erythematosus usually includes potent glucocorticosteroids. However, prolonged use causes adverse side effects including skin atrophy as the foremost concern. In contrast to glucocorticosteroids, the anti-inflammatory and immunosuppressive macrolactam pimecrolimus has no atrophogenic potential. Affected areas of 11 patients with different forms of lupus erythematosus were treated with pimecrolimus 1% cream under semiocclusive conditions twice daily for 3 weeks. Skin involvement before and after therapy was assessed by means of a clinical score. In all patients, significant regression of skin lesions was observed after therapy (P <.001). This was an open and uncontrolled study on a limited number of cases. We suggest that pimecrolimus 1% cream could be an efficacious and safe treatment option for cutaneous lupus erythematosus.

Administration, Cutaneous↗

Pulsed intravenous immunoglobulin therapy in livedoid vasculitis: an open trial evaluating 9 consecutive patients.

BACKGROUND: Livedoid vasculitis (LV) usually presents with painful, slowly healing ulcerations of the lower limbs. The precise pathophysiology of this relatively rare disease remains obscure. Therapeutic strategies usually include rheologic, anti-inflammatory, or immunosuppressive agents. However, no continuing benefit has been reported in any of these modalities. Recently, encouraging case reports about the successful use of intravenous immunoglobulin (IVIg) in LV have been published. METHODS: We initiated an open single center trial to investigate the efficacy and safety of IVIg in LV. Nine patients with LV, 7 of whom were refractory to other treatment modalities, were included. Therapy with IVIg at a dose of 0.5 g/kg body weight per day over 2 or 3 consecutive days was performed monthly. Skin involvement before and after therapy was assessed by means of a clinical score. RESULTS: In all patients, significant regression of skin lesions was observed after therapy resulting in a decrease of the clinical score (including differential semiquantitative assessment of erythema, ulceration, and pain) from 6.5 +/- 1.7 at the beginning to 1.3 +/- 1.2 after therapy (P <.001). IVIg was well tolerated and therapy was finished in all patients. CONCLUSION: In all patients clinical evaluation revealed a marked improvement of erythema, pain, and healing of areas of active ulceration. Although this was an open non-controlled study, we propose that IVIg is a promising therapeutic option in LV refractory to other treatment modalities.

Adult↗

Histomorphologic classification of recurrent saphenofemoral reflux.

OBJECTIVE: The purpose of this study was to determine the apparent mechanisms of recurrent saphenofemoral junction (SFJ) reflux on the basis of the histologic features of intentionally sampled specimens from repeat operations in groins with symptomatic reflux after SFJ ligation and great saphenous vein (GSV) stripping. PATIENTS AND METHODS: Ninety-one samples obtained at repeat operation in patients with symptomatic recurrent groin reflux were evaluated histologically, including the number of venous lumens, the structure of the venous wall, and the surrounding tissue. All repeat operation specimens were obtained in our Department of Vascular Surgery; the original operations in our patients (age 56 +/- 11 years) had been performed in different centers and private practices 12.1 +/- 8.1 years previously. RESULTS: Single-channel recurrence was observed in 63 groins. In 62 the vein wall structure was complex; and 18 demonstrated venous valves. These vessels could be classified as residual stumps of the GSV. Just one single-channel recurrent vessel lined with endothelium and surrounded by scar tissue was detected, and was judged to be neovascular. Multichannel recurrent vessels were found in 28 groins. Twenty-three of these were thin-walled tortuous vessels embedded in scar tissue, and were interpreted as neovascular; 4 were multiple vessels surrounded by fatty tissue and were classified as venule hypertrophy; and 1 was a lymph node that contained numerous channels, and was attributed to lymphovenous connections. CONCLUSION: Original misidentification of the SFJ, as evidenced by an identifiable GSV stump with appropriate histologic features, characterized 68% (62 of 91) of these symptomatic groins. Neovascularity, marked by multiple irregular channels with an incomplete wall structure, was observed in 26% of the groins (24 of 91), accounting for 94% of the recurrent vessels. The findings at repeat operation, supported by analysis of histologic tissue sections, imply that better supervision and training or case concentration in centers of excellence should be more effective in decreasing the incidence of recurrent SFJ reflux after SFJ ligation and GSV stripping than putative operative maneuvers directed at reducing neovascularization.

Adult↗

Unilateral angiokeratoma scroti: a rare manifestation of a vascular tumor.

A 21-year-old patient with a six-year history of asymptomatic papular lesions on his scrotum is reported. The lesions were limited to one half of the scrotum and associated with subclinical varicocele on the same side. The clinical and histopathological findings were consistent with a diagnosis of angiokeratoma scroti. Increased venous pressure caused by the varicocele may have been responsible for the unilateral development of angiokeratoma in this patient.

Adult↗

Morbihan's disease: treatment with CO2 laser blepharoplasty.

Morbihan's disease is a rare condition characterized by chronic persistent erythema and edema of the upper half of the face. Therapeutic regimens such as X-ray irradiation, lymphatic massage, interferon gamma injections, antihistamines, and high-dose antibiotics are often unsatisfactory. Promising results in some patients have been achieved by a systemic combination therapy of isotretinoin with ketotifen or clofazimine. Excision of redundant edematous tissue may be an alternative. We present a 67-year-old Caucasian patient with a two-year history of right lower and upper eyelid swelling and erythema. Systemic therapies with corticocosteroids and antibiotics were not successful, but CO2 laser blepharoplasty led to good cosmetic results with marked improvement of visual impairment and no recurrence during the six-month follow-up period.

Aged↗

Bicentre experience in the treatment of severe generalised atopic dermatitis with extracorporeal photochemotherapy.

Pilot studies have shown an improvement of atopic dermatitis in approximately 65% of patients during extracorporeal photopheresis (ExP) therapy. The purpose of the present clinical trial was to investigate the response to ExP by controlling clinical and laboratory parameters during short term ExP therapy in patients with severe generalised atopic dermatitis. Thirty-five patients with severe, therapy-resistant atopic dermatitis were treated with ExP in an open clinical trial at two week intervals over a period of 6 to 10 cycles. Disease activity was measured before each cycle by SCORAD index together with a standardized protocol for blood samples. ExP led to a significant decrease (p < 0.05) in SCORAD from 74.4 +/- 15.5 before to 36.8 +/- 16.8 after ExP therapy (mean 10 cycles). Approximately 70% (24/33 patients = responder) of patients had a favourable response to ExP requiring at least 6 cycles. The decrease in SCORAD was accompanied by a significant decrease of eosinophil cationic protein (27%), sE-selectin (37%) and sIL-2R (53%) levels in serum (p < 0.05). No significant correlation between a decrease in these levels and values of blood eosinophils or lymphocytes was found (p > 0.05). In comparison to responders, most non-responders were characterised by very high levels of total IgE before and during therapy (p < 0.05). The present clinical trial confirms that short term ExP is an effective treatment for certain patients with severe atopic dermatitis based on anti-inflammatory mechanisms. Total IgE could be a predictor of outcome in ExP treatment.

Administration, Oral↗

Efficacy of different concentrations of ciclopirox shampoo for the treatment of seborrheic dermatitis of the scalp: results of a randomized, double-blind, vehicle-controlled trial.

BACKGROUND: Seborrheic dermatitis is a common inflammatory skin disorder affecting 1-3% of the population. It is thought to be linked to dandruff via a common etiology, yeasts of the genus Malassezia. Ciclopirox is a broad-spectrum, hydroxypyridone-derived, synthetic antifungal agent with anti-inflammatory properties. METHODS: A total of 203 patients were enrolled in this vehicle-controlled, double-blind, randomized study designed to compare vehicle with three different concentrations of ciclopirox shampoo: 0.1%, 0.3% and 1%, with each applied twice a week. The main efficacy parameters were based on 6-point ordinal scales describing the disease's signs and symptoms (scaling, inflammation and itching), global status of disease, and global change in disease. RESULTS: A tendency towards improvement of the sum score from baseline was found in all ciclopirox treatment groups. The most pronounced improvement was found in the ciclopirox 1% group, which changed from a baseline sum score of 8.3 to 4.4 at the end of the 4-week study period (P-value vs. vehicle 0.0372). In addition, the therapeutic index showed increasing efficacy with the use of increased concentrations of ciclopirox. CONCLUSIONS: The study supports the use of 1% ciclopirox shampoo in the treatment of seborrheic dermatitis of the scalp. Furthermore, ciclopirox shampoo at each concentration was found to be safe and well tolerated.

Administration, Cutaneous↗

Capillary blood cell velocity in periulcerous regions of the lower leg measured by laser Doppler anemometry.

BACKGROUND: The capillary blood flow of the nailfold can be measured by means of modern non-invasive techniques like the videocapillary microscope in vivo. To quantify the capillary blood cell velocity, apart from the nailfold capillaries, we used a new technique, the so-called laser Doppler anemometry (LDA). OBJECTIVE: The present study investigated how far laser Doppler fluxmetry (LDF), transcutaneous partial pressure of oxygen (tcpO2), and LDA are capable of quantifying differences of cutaneous microcirculation between patients with leg ulcera and a healthy control group. The effects of intravenous prostaglandin E1 and pentoxifylline were also investigated. PATIENTS AND METHODS: Ten patients with venous leg ulcers and 10 patients with mixed venous/arterial ulcers were investigated with LDF, tcpO2, and LDA before and after injection of prostaglandin E1 and pentoxifylline. We measured the resting capillary blood cell velocity (rCBV), the maximum hyperemia, and the time to peak capillary blood cell velocity (tpCBV) during hyperemia after 4 min of suprasystolic occlusion and compared them with the results of a contol group of 20 patients. RESULTS: Laser Doppler flow was increased in all patients during resting period, whereas the tcpO2 was significantly decreased. LDF did not show an extension of tpCBV during reactive hyperemia after suprasystolic occlusion compared to the control group (73.6+/-31.1 vs. 164.1+/-52.5 s, P=0.003). TcpO2 revealed significantly decreased tpCBV in patients with venous and mixed venous/arterial ulcers (90.1+/-61.7 vs. 162.7+/-65.5 s, P< or =0.0001). LDA showed no significant differences between patients and control group (P>0.8). After application of prostaglandin E1, LDA revealed a significant increase of erythrocyte velocity (0.5+/-0.18 to 0.74+/-0.28 mm/s [P=0,01]), whereas pentoxifylline had no significant effect. Capillary density increased significantly after application of prostaglandin E1 (5,1+/-2.7/mm2 to 8.9+/-3/mm2 [P=0.001]) and pentoxifylline (5.3+/- 1.8/mm2 to 8+/-2.1/mm2 [P=0.006]). CONCLUSION: The LDA is an important additional investigation tool for cutaneous microcirculation.

Aged↗

Premature keratinocyte death and expression of marker proteins of apoptosis in human skin after UVB exposure.

Epidermal keratinocytes undergo a process of terminal differentiation or cornification that in many aspects resembles apoptosis. It is characterized by the elimination of cell nuclei within the granular layer, whereas the cytoplasm is transformed into horn cells. Premature death of keratinocytes can be induced by extrinsic factors such as UV irradiation. We investigated the time-dependent expression of apoptotic marker proteins in the skin of one healthy human volunteer after irradiation with a fourfold minimal erythema dose (MED) of UVB. The data were supplemented by including healthy skin areas of biopsies from patients UVB-irradiated for therapeutic reasons. Punch biopsies were analysed by in situ end-labelling (ISEL) for DNA strand breaks and by immunohistochemistry for expression of p53, bcl-2, active caspase-3 and its proform, and deoxyribonuclease I (DNase I). Keratinocytes with pyknotic nuclei were first detected 6 h after UVB exposure, and apoptotic keratinocytes (sunburn cells) 12 h after exposure. These aggregated to sunburn bodies after 24 h. In control skin, nuclei with DNA strand breaks were only occasionally detected in the granular layer but 6 h after UVB irradiation in the spinous layer. After 12 h, many sunburn cells were ISEL-positive and positively stained for active caspase-3, P53, and DNase I. Morphometric evaluation of the immunohistochemical data demonstrated that maximal upregulation of P53, DNase I and activation of caspase-3 occurred 12 h after irradiation and in advance of the peak of apoptotic cell death reached after 24 h as verified by ISEL. In contrast, strong Bcl-2 immunostaining appeared restricted to presumed melanocytes and basal cells but was not increased after UVB irradiation.

Adult↗