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Biomedical subjects

M Kaatz

Publications and source records attributed to M Kaatz.

At least 19 recordsLinked to original sources

Microtubules regulate expression of ICAM-1 in epidermoid cells (KB cells).

The intercellular adhesion molecule-1/CD54 (ICAM-1) functions as a counterreceptor for other adhesion molecules (e.g. the lymphocyte function-associated antigen-1/CD11a/CD18) required for the interaction of a large variety of cells with leucocytes. Constitutive expression of ICAM-1 in human epidermoid cells (KB cells) is low, but inducible by interferon-gamma (IFN-gamma). Treatment of KB cells with microtubule-disrupting agents, like colchicine, nocodazole and vinblastine, potentiated the constitutive and cytokine-induced ICAM-1 expression on the cell surface. Actinomycin D inhibited microtubule-disrupting agent-induced ICAM-1 surface expression. Increased steady-state levels of ICAM-1 transcripts were found after treatment of KB cells with microtubule-disrupting agents. However, microtubule-disrupting agents neither altered the glyceraldehyde-3-phosphate dehydrogenase mRNA levels nor the amount of expressed alpha(2)-, alpha(3)-and beta(1)-integrins at the cell surface. In addition, they did not change the ICAM-1 mRNA half-life. These studies indicate a control function of the microtubule network on the expression of ICAM-1.

Antineoplastic Agents↗

Cutaneous Langerhans cell histiocytosis with subsequent development of haematological malignancies. Report of two cases.

Adult cutaneous Langerhans cell histiocytosis (LCH) is a rare disease. We report two cases illustrating the variability of the clinical presentation and the response to treatment. In both cases a remission was achieved: in one case a partial remission with psoralen plus UVA irradiation (PUVA) and methotrexate plus topical corticosteroid ointment; in the other case by treatment with thalidomide. Despite a therapeutic response, both patients later developed haematological malignancies: a chronic myelo-monocytic leukaemia and an acute lymphatic leukaemia. In conclusion, patients with adult cutaneous LCH should be monitored carefully so that a secondary malignancy is not overlooked.

Adult↗

Vulvar dermatoses--irritant and allergic contact dermatitis of the vulva.

Irritant and allergic contact dermatitis are commonly seen in patients complaining about itching, burning and irritation in the vulvar area. Irritation often precedes allergic sensitization. Clinically, irritant and allergic contact dermatitis can be difficult to distinguish. Diagnosis is made by history, clinical investigation and patch testing. Recommended patch test series are the standard series, a medicament series, the patient's own topical medicaments, popular remedies and other suspected products. A skin biopsy may be useful to establish the diagnosis of contact dermatitis, but it is usually not helpful for the differential diagnosis between irritant and allergic dermatitis.

Allergens↗

Successful treatment of cutaneous langerhans cell histiocytosis with thalidomide.

Langerhans cell histiocytosis (LCH) represents a group of rare histiocytic syndromes characterized by tissue infiltration with dendritic cells. The management of LCH is difficult as these disorders respond inconsistently to immunosuppressive and chemotherapeutic strategies. Thalidomide (N-phtalimidoglutarimide), initially used as a tranquilizer, has recently been used in the management of several inflammatory skin diseases. We describe the case of a 38-year-old male with mucocutaneous LCH. A treatment course with 6 cycles of 2-chlorodeoxyadenosin (cladribine) was initiated. This was well tolerated but withdrawn after 6 months to prevent secondary malignancy. A partial remission was seen. Subsequently, a treatment course with thalidomide 200 mg daily was started. This therapy resulted in a significant improvement of the mucocutaneous lesions within 4 weeks and complete healing was achieved after 3 months. Treatment was then successfully continued with daily doses of 100 mg to prevent relapse. In conclusion, thalidomide monotherapy represents an effective, safe and well-tolerated treatment option that should be considered as first-line therapy for mucocutaneous LCH.

Administration, Oral↗

Clinical phase II study of pegylated liposomal doxorubicin as second-line treatment in disseminated melanoma.

BACKGROUND: Stage IV melanoma has a poor prognosis with a median survival of 3-11 months from diagnosis of distant metastases. Response rates in first-line regimens range around 15-20%. Non-responders have a median survival around 6 months. Currently, no second-line treatment in advanced melanoma has been established. PATIENTS AND METHODS: In a clinical phase II study we evaluated the efficacy of liposomal doxorubicin (Caelyx) in 30 patients (17 m, 13 f) with progressing metastatic melanoma who had failed a previous chemotherapy. Liposomal doxorubicin was given in an outpatient setting at a dose of 50 mg/m2 i.v. on d1, d22, d43 and d64, subsequently at 40 mg/m2 at d85 before first staging and in 4-week intervals thereafter. Treatment was very well tolerated with 100 cycles given in total. Response rate, survival time, time-to-progression and toxicity were assessed. RESULTS: Erythrodysesthesia was the most severe toxicity in 6% at CTC grade 3. Liposomal doxorubicin was of limited clinical efficacy with 21 patients progressing within the first 12 weeks. However, 7 patients were treated 3-9 months and were stable for >90 days, achieving 5 SD, 1 PR and 1 CR. Median survival after initiation of second-line treatment was 214 days (95% CI: 151-304 days) with 7 patients surviving >300 and 5 patients >400 days. CONCLUSIONS: Liposomal doxorubin as monotherapy is well tolerated but of limited clinical efficacy. Whether the survival benefit of a significant proportion of patients (20%) holds true in larger cohorts and whether the efficacy of liposomal doxorubicin can be improved by combinations without compromising the low toxicity profile needs further studies.

Adult↗

Erythema induratum of Bazin and Poncet's disease -- successful treatment with antitubercular drugs.

Erythema induratum of Bazin (EIB) is considered a tuberculide reaction and consists of recurrent painful nodules predominantly on the calves. Clinically it has common features with diseases like nodular vasculitis, perniosis, polyarteritis nodosa and erythema nodosum. Poncet's disease is a reactive arthritis that may accompany tuberculosis. We report a case of a young woman in which the simultaneous occurrence of erythema induratum of Bazin and Poncet's disease led to a clinical picture very similar to Löfgren's syndrome. The final diagnosis was obtained by polymerase chain reaction detection of mycobacterial DNA in a skin biopsy. A systemic therapy with tuberculostatic drugs led to the disappearance of symptoms. The presented case shows the usefulness of polymerase chain reaction diagnostics in EIB patients without other clinical signs of tuberculosis and a confusing combination of symptoms, and further confirms the presence of mycobacterial DNA in EIB lesions.

Adult↗

[Subungual chondroma, a case report].

Subungual chondroma is a rare occurrence of periosteal chondroma, which mainly affects short tubular bones of the hands and feet. Transformation towards malignancy has been described in a small number of cases; however histologic diagnosis can prove to be difficult, especially with regard to well differentiated chondrosarcoma. We report the case of a 14 year old girl with a one year history of subungual chondroma of the fourth toe with good clinical response to surgical removal.

Adolescent↗

[Circumscribed hypertrichosis lanuginosa in acute myeloid leukemia].

HISTORY AND CLINICAL FINDINGS: The case of a 70 year old male is presented. Past medical history revealed the following diagnoses: liver cirrhosis, splenomegaly, thrombocytopenia, macrocytic anaemia, chronic obstructive pulmonary disease, type IIa diabetes mellitus and peripheral vascular disease of the lower limbs with chronic leg ulcers. Within 6 weeks the patient developed an increasing number of pigmented lanugo type hair over both cheeks, zygomatic arches and temples. The diagnosis of circumscribed acquired hypertrichosis lanuginosa (AHL) was established. Bone marrow biopsy revealed presence of acute myeloid leukemia. THERAPY AND CLINICAL COURSE: Chemotherapy with hydroxycarbamide (Syrea) was started without effect on haematologic parameters. The patient was transferred to the oncology unit where he died soon afterwards. CONCLUSION: Acquired hypertrichosis lanuginosa (AHL) is a paraneoplastic syndrome. It is mainly associated with adenocarcinoma of lung and bowel, however other histologic types of tumours and localisations have been described. About 50 cases have been reported in the literature until 1998. To our knowledge this is the first case of AHL described in association with acute myeloid leukemia.

Acute Disease↗

Pegylated doxorubicin for primary cutaneous T-cell lymphoma: a report on ten patients with follow-up.

PURPOSE: Pegylated liposomal doxorubicin (PEG-DOXO) was found to be effective in primary cutaneous T-cell lymphomas (CTCL). The present observation reports on follow-up and relapse-free interval in patients with CTCL. METHODS: Ten patients (one female, nine male) aged 50-78 years (mean 66.7 years) with relapsing or recalcitrant CTCL, stage I b (n = 3), II a (2), II b (3), IV a (1), and IV b (1) were treated with PEG-DOXO 20 mg m(-2) once a month with an upper limit of 400 mg or eight infusions to induce a clinical response. There was one drop out after a single infusion because of a capillary leak syndrome. RESULTS: In nine patients with PEG-DOXO the best response was a complete response (CR) in five patients and a partial response (PR) in four patients. The final outcome was CR in six, PR in two, stable disease (SD) in one, and progressive disease (PD) in another patient. The overall response rate (CR + PR) was 80% (of ten patients). The follow-up was 2-22 months (mean 12.8+/-7.1 months). The overall survival was calculated as 19.8+/-7.4 months with eight out of ten patients still alive. Response duration was 15.2+/-3.9 months, disease-free survival 13.3+/-6.1 months, event-free survival 16.7+/-9.0 months, and progression-free survival 18.2+/-6.5 months. Four patients (stage I b and II b) achieved 12-19 months of disease-free survival. The follow-up after the first course with PEG- DOXO was 2-22 months (mean 12.8+/-7.1 months). The survival rate after 12 months of follow-up was 80% (n = 5). One patient free of relapse died after 12 months because of pulmonary embolism not related to disease or treatment. Another patient died 1 month after a second course of PEG-DOXO in an advanced tumor stage of CTCL. The most frequent side effects of treatment were anemia and lymphopenia without the need of supportive treatment or dose-reduction. Only one patient developed toxicity of grade 4 (anemia). CONCLUSIONS: These results indicate that patients with relapsing or recalcitrant CTCL can achieve an 80% response rate with PEG-DOXO and long-term remissions.

Adult↗

Angiosarcoma of the scalp: treatment with liposomal doxorubicin and radiotherapy.

PURPOSE: Angiosarcoma of the scalp and face is a rare malignant endothelial tumor arising mainly in elderly people. The prognosis is poor. Effective and safe treatments are warranted. METHODS: A 79-year-old woman with an angiosarcoma of the scalp larger than 5 cm in diameter was treated with intravenous liposomal doxorubicin, 20 mg per square meter body surface (i.e., 30 mg) once per month followed by radiotherapy. RESULTS: After 12 infusions of liposomal doxorubicin, we observed a partial remission with a > 50% decrease of affected area and disappearance of ulceration. After 21 infusions, however, there was no further improvement. We decided to discontinue chemotherapy but move on with radiotherapy with an electron beam using fractionated doses of 2 Gy five times per week for up to a total of 40 Gy. To ensure a maximum dose in the upper layer of the dermis a bolus technique was used. Radiotherapy was terminated due to a temporary circumscribed epidermolysis. At the end of treatment a remarkable regression of the cutaneous lesion was noted. During the subsequent 24 months she has not developed any metastatic spread. CONCLUSION: Sequential therapy of bad prognosis angiosarcoma with liposomal doxorubicin followed by radiotherapy showed a marked clinical improvement and prolonged relapse-free survival in this patient.

Aged↗

Serum matrix metalloproteinase-2 in patients with malignant melanoma.

PURPOSE: Matrix metalloproteinases (MMPs) are a family of structurally related zinc-dependent endopeptidases that are able to degrade extracellular matrix components. MMPs play a role in tumor invasion and tumor metastasis. MMP-2 (also known as gelatinase A) is expressed in human melanoma cells. METHODS: In this study, we measured MMP-2 in 337 serum probes of 166 melanoma patients with a recently developed enzyme immunoassay and compared these data with the tumor stage, presence of metastases, and the levels of S100beta and soluble intracellular adhesion molecule-1 (sICAM-1) in serum. RESULTS: The mean levels were (189.2 +/- 50.8) ng/ml for MMP-2, (263.2 +/- 74.1) ng/ml for sICAM-1, and (0.424 +/- 1.568) U/ml for S100beta. There was a statistical significant correlation of MMP-2 with sICAM-1 (P=0.05) and Sl00beta (P=0.01). The mean MMP-2 levels (in ng/ml) in patients with metastatic melanoma were 196.4 +/- 54.0 versus 182.6 +/- 46.9 in non-metastasizing melanoma (P=0.037). However, there was no significant difference in MMP-2 levels between the different tumor stages. CONCLUSION: Determination of MMP-2 serum levels is of limited value as a tumor marker in melanoma, though there are higher levels in the more advanced disease.

Adult↗

[Late manifestation of a fatal Behçet's disease with cardiac involvement and lethal outcome].

HISTORY AND CLINICAL FINDINGS: One year before admission a 67-year-old man of German origin developed extensive ulcerations of the limbs, later also of the trunk and neck. In addition to recurrent oral aphthous ulcers it was associated with erythema nodosum and intermittent arthritis of the elbow knee and ankle joints. During the last month he also had dyspnoea. Echocardiography revealed a dilated cardiomyopathy (DCM). He was admitted because of the progressive skin disorder. Physical examination showed a disoriented man with dyspnoea, cyanosis of the lips and pretibial oedema. He had aphthous ulcers in the mouth and on the genitals. Adamant Behçet disease was suspected. INVESTIGATIONS: Erythrocyte sedimentation rate was raised to 21/48 mm/h, white cell count to 15,800/microliter. Tests for HLA B5 and B27 were negative, skin biopsy revealed superficial necrotizing vasculitis of postcapillary venules. TREATMENT AND COURSE: Initially high doses of prednisolone, 100 mg/d intravenously) and azathioprine (100 mg/d orally) were administered, and within a few days both the skin and cardiac changes had regressed. Prednisolone dosage was reduced and cyclosporin (350 mg/d) substituted for azathioprine. He was discharged in a markedly improved general condition and with only a few tibial ulcerations. 4 months later he had a severe recurrence with dramatic mucocutaneous involvement and rapidly deteriorating DCM, together with radiological signs of pneumonia. He died 4 months later. INTERPRETATION: Although very rare, Behçet disease should even in the elderly patients be considered in the differential diagnosis: in the presence of appropriate symptoms cardiac involvement should be looked for.

Aged↗