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Biomedical subjects

T M Proebstle

Publications and source records attributed to T M Proebstle.

26 records · Page 2Linked to original sources
PubMed1997

Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.

PURPOSE: The combination of interferon alfa-2a (IFN alpha) and high-dose interleukin-2 (IL-2) is active in metastatic melanoma. The addition of cisplatin (CDDP) has resulted in response rates greater than 50%. This study was performed to determine whether the addition of CDDP to a cytokine treatment regimen with IFN alpha and high-dose IL-2 influences survival of patients with metastatic melanoma. PATIENTS AND METHODS: Patients with advanced metastatic melanoma were randomly assigned to receive treatment with IFN alpha 10 x 10(6) U/m2 subcutaneously on days 1 through 5 and a high-dose intravenous decrescendo regimen of IL-2 on days 3 through 8 (18 mIU/ m2/6 hours, 18 mIU/m2/12 hours, 18 mIU/m2/24 hours, and 4.5 mIU/m2/24 hours x 3) without (arm A) or with (arm B) CDDP 100 mg/m2 on day 1. Treatment cycles were repeated every 28 days to a maximum of four cycles. RESULTS: One hundred thirty-eight patients with advanced metastatic melanoma, of whom 87% had visceral metastases, were accrued for the trial. Both regimens were feasible in a multicenter setting. The objective response rate was 18% without and 33% with CDDP (P = .04). The progression-free survival was 53 days without and 92 days with CDDP (P = .02, Wilcoxon; P = .09, log-rank). There was no statistically significant difference in survival between treatment arms, with a median overall survival duration for all patients of 9 months. CONCLUSION: The addition of CDDP to cytokine treatment with IFN alpha and IL-2 does not influence survival of patients with advanced metastatic melanoma, despite a significant increase in response rate and progression-free survival.

Antineoplastic Agents↗
PubMed1996

[Behçet disease with primary involvement of the cerebral vessels].

HISTORY AND CLINICAL FINDINGS: Two months after the onset of mainly frontal headaches a 25-year-old man of Turkish descent additionally developed double vision. Fundoscopy revealed bilateral choked discs and right trochlear paralysis. Computed tomography and digital subtraction angiography demonstrated thrombosis of the superior sagittal sinus. On admission to hospital the patient was fully conscious but had marked meningism, bilaterally positive Lasègue's sign (painful straight leg raising) at a 50 degree angle, and multiple oral aphthous ulcers. The sinus thrombosis suggested a chronic inflammatory process, while the oral ulcers pointed to Behçet's syndrome. INVESTIGATIONS: Inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein and white blood cell count) were increased and the HLA-B27 test was positive. Other laboratory tests, cerebrospinal fluid, chest radiogram and ECG were unremarkable. TREATMENT AND COURSE: Despite intravenous administration of heparin nad cefuroxim for one week the sagittal sinus thrombosis spread to the straight sinus. In the third week scrotal ulcerations were noted and taken to confirm Behçet's syndrome. Immunosuppressive treatment with methylprednisolone (initially 80 mg daily) and 2 weeks later together with chlorambucil (0.1 mg/kg daily) was started. Four weeks later the patient was free of symptoms and discharged. CONCLUSION: Neurological signs are not adequately stressed by the International Study Group for Behçet's Disease among its listed diagnostic criteria.

Adult↗
PubMed1996

Identification of lymph node metastases by use of polymerase chain reaction (PCR) in melanoma patients.

Diagnosis of clinically suspected lymph node metastases in melanoma patients can be confirmed with high sensitivity and specificity by fine needle aspiration (FNA) cytology. However, small lymph nodes or haemorrhagic metastases may yield negative or unevaluable cytology. We tested whether the sensitivity and specificity of presurgical diagnosis could be improved by a polymerase chain reaction (PCR) method, identifying tyrosine-mRNA in samples obtained by fine needle aspiration (FNA-PCR). PCR was positive in 17 of 18 histopathologically proven melanoma metastases, while conventional cytopathology detected 16 of 18. 4 of 9 disease-free melanoma patients with negative FNA cytology had positive PCR results, but controls gave negative results. FNA-PCR analysis cannot be recommended as superior to conventional FNA cytological examination. Whether the positive FNA-PCR in four of the nine clinically unsuspicious regional lymph nodes correlates with earlier disease progression or indicates lower specificity of the method will need further investigation.

Base Sequence↗
PubMed1996

Detection of early micrometastases in subcutaneous fat of primary malignant melanoma patients by identification of tyrosinase-mRNA.

To improve survival following melanoma excision, wide margin resection including subcutaneous fat, is indicated. Subcutaneous fat, resected with primary melanomas, was investigated using the tyrosinase PCR method originally described for detection of melanoma cells in peripheral blood. Identification of tyrosinase transcripts was possible in 4 melanoma patients (3 Clark level IV, 1 level III), while negative results were obtained from 6 other patients (2 level IV, 3 level III and 1 level I). In control experiments, after infiltration of the reference cell line SkMel into normal fat tissue, the PCR was positive in 33% (3/9) with 10(2) infiltrated cells, 69% (9/13) with 10(4) cells and in 100% (7/7) with 10(6) cells. We conclude that detection of melanoma cells in subcutaneous fat tissue is possible by tyrosinase PCR. Follow-up studies should show whether such positive tyrosinase PCR can define patients at very high risk of tumour relapse.

Adipose Tissue↗
PubMed1996

A phase II study of dacarbazine, cisplatin, interferon-alpha and high-dose interleukin-2 in 'poor-risk' metastatic melanoma.

Melanoma patients with very advanced disease have usually not been included in chemo-immunotherapy trials. We report on 22 melanoma patients, including 5 with reduced performance status (Karnofsky PS < 70), 8 with metastatic ocular melanoma, 6 with brain metastases, and 4 who had pretreatment with interleukin-2. These were treated with a combination regimen of dacarbazine (250 mg/m2, days 1-3), cisplatin (30 mg/m2, days 1-3), interferon-alpha 2a (IFN-alpha, 10 Mio IU/m2 s.c., days 1-5) and IL-2 (i.v., 18 Mio IU/m2 for 6, 12, 24 h, followed by 13.5 Mio IU/m2 in 72 h). In the case of brain metastases radiotherapy was added. No grade IV toxicity occurred and no dose reductions were necessary. 21 patients were evaluable for response. 6 (29%) had disease progression, 5 (24%) had partial response and 10 (48%), had stable disease. Sites of response included skin, lymph nodes, muscle, lung, pleura, liver, pancreas, adrenal gland and brain. The described treatment schedule is safe and active even in patients with metastatic melanoma and poor prognosis.

Adult↗
PubMed1995

[Calciphylaxis].

HISTORY AND CLINICAL FINDINGS: Acute, zigzag-shaped livid skin markings developed on both thighs of a 55-year-old woman who had been on dialysis for 6 years. Within 7 days these areas increased in size to about 10 cm in diameter and contained central dry and painful necroses. On legs, lower arms and hands hard subcutaneous nodules were palpable with a diameter up to 3 mm. For many years the phosphate and parathormone levels, as well as alkaline phosphatase activity had been raised. The patient had often failed to follow treatment recommendations. TESTS: There were increased serum concentrations of calcium (2.8 mmol/l) and phosphate (1.78 mmol/l). The calcium phosphate ion product was 4.98 (mmol/l)2. Furthermore, there were raised levels of alkaline phosphatase (315 U/l) and parathormone (1076 ng/l, normal: 10-65). X-ray film of the hands showed soft tissue and arterial calcifications, while histological examination of a deep skin biopsy revealed calcium phosphate emboli of the main vessels. TREATMENT AND COURSE: Excision of the cutaneous necroses was followed by parathyroidectomy at which only three parathyroid glands were identified and removed. The parathormone level fell postoperatively, but rose again after 4 weeks. The fourth parathyroid gland was then found and removed, after which the parathormone level fell below measurable levels. The skin ulcers healed completely 4 weeks after the second operation.

Calciphylaxis↗