PubMed Health⌕ Search

Biomedical subjects

S Hosch

Publications and source records attributed to S Hosch.

7 recordsLinked to original sources

Better late than never? Experience with intravenous pamidronate treatment in patients with low bone mass or fractures following cardiac or liver transplantation.

Organ transplantation is associated with a high turnover of bone metabolism, and an increased loss of bone mass and incidence of osteoporotic fractures. Established therapies for osteoporosis after organ transplantation are still lacking, however. We report on an intravenous bisphosphonate therapy initiated in transplant patients because of a high rate of bone loss or incident osteoporotic fractures. Twenty-one patients after liver transplantation and 13 patients after heart transplantation received 30 mg pamidronate intravenously every 3 months, combined with 1000 mg calcium and 1000 IU vitamin D per day. The median time interval between transplantation and start of pamidronate treatment was 1.9 years in cardiac patients and 2.3 years in liver patients. Lumbar spine bone mineral density (LS BMD) and femoral neck BMD (FN BMD) were measured before and every 6 months after pamidronate therapy was initiated. Spinal radiographs were performed annually. Biochemical markers of bone metabolism were determined every 3 months, immediately before pamidronate administration. From a previous observational study, 58 patients treated only with calcium and vitamin D were matched for age, sex, pretransplantation LS BMD and time interval between transplantation and the first pamidronate treatment. In the pamidronate-treated patients, the mean increase in LS BMD adjusted for baseline values amounted to 0.080 +/- 0.038 g/cm(2) (8.6 +/- 4.0 %) after 1 year and 0.091 +/- 0.058 g/cm(2) (10.4 +/- 6.1%) after 2 years compared with 0.001 +/- 0.037 g/cm(2) (0.26 +/- 4.0%) after 1 year and 0.015 +/- 0.057 g/cm(2) (1.8 +/- 6.0%) after 2 years in the historical control group (absolute LS BMD changes pamidronate group vs historical group p < 0.0001 after 1 and 2 years). The changes of FN BMD were 0.024 +/- 0.043 g/cm(2) (3.2 +/- 6.1%) after 1 year and 0.046 +/- 0.052 g/cm(2) (7.0 +/- 6.1%) after 2 years in the pamidronate group compared with -0.012 +/- 0.043 g/cm(2) (-1.6 +/- 6.1%) after 1 year and -0.013 +/- 0.052 g/cm(2) (-1.1 +/- 6.1%) after 2 years in the historical control group (absolute FN BMD changes pamidronate group vs historical group p = 0.003 after 1 year and p = 0.001 after 2 years). From a total of 287 application cycles of pamidronate treatment, no severe side effects were observed and non-severe side effects were seen in only 39 cycles (13.6%). We conclude that cyclic intravenous pamidronate treatment is beneficial to patients with low bone mass or osteoporotic fractures following transplant, even when not immediately initiated.

Adult↗

Expression of HER2/neu does not correlate with survival in soft tissue sarcoma.

BACKGROUND: The expression of HER2/neu has been identified as a prognostic factor in several malignant diseases. However, only sparse data exist correlating HER2/neu expression in soft tissue sarcoma with subsequent tumor progression or recurrence. The purpose of this study was to investigate the clinical significance of HER2/neu in adult soft tissue sarcoma (STS). METHODS: Tumor specimens of patients with STS were evaluated regarding HER2/neu expression using immunohistochemistry. The significance of the proposed prognostic indicators was evaluated in relation to survival and local recurrence. RESULTS: Of 62 analyzed specimens, 43 tumors were HER2/neu negative compared to 19 HER2/neu positive tumors. Kaplan-Meier analysis indicated no difference in survival according to HER2/neu expression (p = 0.31, log-rank test = 1.10). Variables that were predictive of longer survival included better resection quality (R0, p < 0.01) and smaller tumor size (T1, p = 0.02). CONCLUSION: HER2/neu expression does not correlate with prognosis of soft tissue sarcomas. Its evaluation for tumor prognosis as well as for the identification for adjuvant therapeutic strategies does not appear warranted at this point.

Adult↗

[The Internet as a source for information retrieval. Example: soft tissue sarcoma].

INTRODUCTION: Due to increasing availability, easier access, and rapid growth of information, the Internet has become an important source of medical information. We analyzed the value of Internet sites and the content of their medical information for physicians and patients using the example "soft tissue sarcoma." METHODS: Sixteen German and English Internet search engines were used to evaluate the retrieved internet sites regarding their target group, publisher, contents, and topicality. RESULTS: The majority of retrieved websites were in English compared to significantly fewer in German. The content of information was more valuable for patients and physicians on the English websites compared to the German ones. Even if many of the evaluated websites originated from medical organizations or universities, the amount of information was limited and often not up to date. CONCLUSION: Information on the web is widespread, but for special queries too limited and difficult to identify. An improvement of available websites is needed, especially those maintained by universities and nonprofit medical organizations. The retrieval software should be optimized to ease identification of information, which should be validated by a recognized standard.

Humans↗

Frequency and predictors of osteoporotic fractures after cardiac or liver transplantation: a follow-up study.

BACKGROUND: Osteoporosis and related fractures are a major complication after organ transplantation. The aim of this study was to find out the frequency and predictors of osteoporotic fractures after cardiac or liver transplantation. METHODS: 235 consecutive patients who had a cardiac transplant (n=105; 88 men, 17 women) or a liver transplant (130; 75 men, 55 women) were followed. Vertebral fractures were assessed by a standardised analysis of spinal radiographs before and annually after transplantation. Clinical and non-vertebral fracture data were noted from hospital records. FINDINGS: In the first and second years after transplantation, the proportion of patients (Kaplan-Meier estimates) who had at least one vertebral fracture was slightly higher in the cardiac group (first year 21%, second year 27%) than in the liver group (first year 14%, second year 21%). In the third and fourth years, one third of patients from both groups had had one or more vertebral fractures. Non-vertebral fractures occurred in nine patients (7%) after liver transplantation and avascular necrosis of the hip head in three patients (3%) after cardiac transplantation. In both groups, no dose-dependent effect of immunosuppressive therapy on fracture development could be identified. Independent predictors assessed by multivariate analysis were age (hazard ratio [95% CI] increase of 5 years, 1.71 [1.1-2.7]) and lumbar bone-mineral density (decrease of 1 SD t score, 1.97 [1.2-3.2]) in cardiac transplantation patients, and vertebral fractures before transplantation (6.07 [1.7-21.7]) in the liver group. INTERPRETATION: The high frequency of osteoporotic fractures in the 2 years after transplantation and the limitations of reliable fracture-risk predictions, show the need to investigate preventive therapies.

Adult↗

Malignant potential and cytogenetic characteristics of occult disseminated tumor cells in esophageal cancer.

Although micrometastatic cancer cells in lymph nodes can be detected by monoclonal antibodies against epithelial or tumor-associated antigens, it remains unclear whether these cells are precursors of overt metastases or shedded tumor cells with a limited life span. Here we used esophageal cancer as a model to evaluate the prognostic significance and biological characteristics of such micrometastases. In lymph nodes classified as tumor free by conventional histopathological staging, tumor cells were identified with monoclonal antibody Ber-EP4 in 89 of 126 patients (71%) with completely resected (R0) esophageal carcinomas. Multivariate survival analysis underlined the strong and independent prognostic significance of Ber-EP4-positive cells in "node-negative" (pN0) patients. To assess the biology of Ber-EP4-positive cells, we established tumor cell lines from an immunohistochemically positive lymph node and the autologous primary tumor. p53 mutational analysis and multiplex-fluorescence in situ hybridization revealed common aberrations shared between both cell lines, whereas an insertion of chromosome 13 material in the short arm of chromosome 1 was only observed in micrometastatic cells. The tumorigenicity and metastatic potential of both cell lines were demonstrated in severe combined immunodeficient mice. In conclusion, our data provide first direct evidence for the malignant potential of micrometastatic cancer cells.

Adenocarcinoma↗

Specificity of reverse transcriptase polymerase chain reaction assays designed for the detection of circulating cancer cells is influenced by cytokines in vivo and in vitro.

Several reverse transcriptase polymerase chain reaction (RT-PCR) assays have been described for the detection of circulating tumour cells in blood and bone marrow. Target mRNA sequences for this purpose are the cytokeratins (CK) 19 and 20, the carcinoembryonic antigen (CEA), and the prostate-specific antigen messages. In this study, we investigated biological factors influencing the specificity of the CK19 and CEA RT-PCR assays. Bone marrow, granulocyte colony-stimulating factor (G-CSF)-mobilized blood stem cells and peripheral blood samples obtained from healthy volunteers (n = 15; CEA n = 7), from patients with epithelial (n = 29) and haematological (n = 23) cancer and from patients with chronic inflammatory diseases (n = 16) were examined. Neither CEA nor cytokeratin 19 messages could be amplified from bone marrow samples from healthy subjects and from patients with haematological malignancies. In contrast, specimens from patients with inflammatory diseases scored positive up to 60%. To investigate the influence of inflammation on target mRNA expression, haemopoietic cells were cultured with and without cytokine stimulation in vitro. CK19 messages could be easily detected in cultured marrow cells without further stimulation, CEA messages only after gamma-interferon (gamma-INF) stimulation. In contrast, G-CSF-mobilized peripheral blood stem cells were positive for CK19 messages only after stem cell factor (SCF) or interleukin stimulation. We conclude that transcription of so-called tissue-specific genes is inductible in haemopoietic tissues under certain conditions. These factors have to be considered in future applications of RT-PCR for the detection of minimal residual disease.

Abdominal Neoplasms↗

[Expression of plakoglobin in bronchial carcinomas: incidence and significance for disease outcome].

Loss of homotypic cell adhesion is an important prerequisite for invasion and metastasis of epithelial tumor cells. The function of E-cadherin, which mediates epithelial cell-cell adhesion, is regulated by a complex of proteins bound to its cytoplasmic tail, including a-, b-, g-catenins and plakoglobin (PG). The present study was designed to assess whether downregulation of plakoglobin expression occurs in human non-small cell lung carcinomas (NSCLC) and whether this change is associated with an unfavorable prognosis. Using immunohistochemistry with monoclonal antibody (mAb) PG 5.1 to PG, absence or severely reduced expression of PG (i.e., less than 30% of positive tumor cells) was observed in 39 of 97 patients (40.2%) with completely resected primary NSCLC (stages T1-3, N1-2, M0). There was no significant correlation to any of the analyzed clinicopathologic factors such as histologic type, grade or size of the primary tumor, and lymph node involvement. After a median observation period of 39 months (12-56 mo.), univariate Kaplan-Meier analysis showed that patients with PG-deficient primaries tended to have a shortened disease-free survival (p = 0.06). This correlation was statistically significant in patients with adenocarcinomas (p = 0.010), locally restricted primary tumors (pT1/2, p = 0.017), and negative lymph nodes (pN0, p = 0.036). Analysis of the overall survival in these subgroups also revealed significant associations between deficient PG expression and poor outcome (p < or = 0.036). Multivariate analysis was performed for the largest subgroup of patients with pT1/2 tumors (n = 66), demonstrating that PG expression was a strong, independent predictor of tumor relapse (p = 0.002). Thus, deficient expression of PG is a frequent, early event in the progression of NSCLC, which appears to predict an unfavorable prognosis in patients at earlier stages of their disease.

Adult↗