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Biomedical subjects

C Neumann

Publications and source records attributed to C Neumann.

At least 55 records · Page 3Linked to original sources

Superficial inguinal and radical ilioinguinal lymph node dissection in patients with palpable melanoma metastases to the groin--an analysis of survival and local recurrence.

The present study addresses the question whether an extended ilioinguinal dissection as compared to an only superficial inguinal dissection improves survival and/or local tumour control after the appearance of palpable melanoma metastases to the groin. We retrospectively analysed the data of 104 patients with 69 ilioinguinal and 35 superficial inguinal dissections (median follow up 127 months). Prognostic factors of survival and groin recurrence were assessed using Kaplan-Meier estimation and Cox proportional hazards model. By multifactorial analysis, metastatic involvement of two lymph nodes or less was associated with a significantly better survival rate than involvement of > 2 or pelvic nodes (p = 0.0002). After radical ilioinguinal dissection, patients with extremity-located primaries had a better prognosis than patients with truncal primaries (p = 0.03). Tumour infiltration of the ilio-obturator compartment was found to be an independent factor of poor prognosis (p = 0.0009). The probability of recurrence in the dissected groin paralleled the number of positive nodes and significantly increased if intransits were observed (p = 0.0002). The extent of surgery, Breslow thickness, epidermal ulceration, sex, age and adjuvant chemotherapy neither significantly influenced survival nor local control rates. In summary, when metastatic inguinal nodes become palpable, the presence of pelvic metastases indicates systemic disease. After therapeutic groin dissection, local recurrence and survival depend rather on regional tumour burden than on the extent of surgery.

Female↗

Spinal metastases from renal cell carcinoma: effect of preoperative particle embolization on intraoperative blood loss.

BACKGROUND AND PURPOSE: Surgical repair of spinal metastases from renal origin is often complicated by excessive bleeding. The purpose of this study was to assess the effect of preoperative particulate embolization on intraoperative blood loss. METHODS: Twenty spinal metastases from renal origin (17 patients) treated by preoperative embolization with polyvinyl alcohol particles were analyzed retrospectively. Surgical decompression was performed within 2 days after embolization. A control group of 10 patients with 11 spinal metastases of renal origin underwent surgery without embolization. The effect of preoperative embolization, of completeness of embolization, and of particle size on the estimated intraoperative blood loss was analyzed using nonparametric statistical tests. RESULTS: Complete embolization was achieved in 10 cases and partial embolization in the other 10. The estimated blood loss of 19 embolized and 11 control cases was available from the surgical report. Median intraoperative blood loss in 19 embolized lesions was 1500 mL (range, 300-8000 mL), compared with 5000 mL (range, 1440-15000 mL) in the control group. Even after partial embolization, blood loss (median, 2000 mL) was significantly lower than in the control group. No significant differences in estimated blood loss were noted between the use of particles smaller than 250 microm and those larger than 250 microm. No embolization-related permanent neurologic deficit or skin or muscle necrosis occurred. CONCLUSION: Preoperative embolization of spinal metastases of renal origin with polyvinyl alcohol particles is safe and might reduce intraoperative blood loss significantly. Even partial embolization seems to be effective.

Aged↗

In vitro and in vivo antitumor effect of the anti-CD26 monoclonal antibody 1F7 on human CD30+ anaplastic large cell T-cell lymphoma Karpas 299.

CD26 is a M(r) 110,000 surface glycoprotein with diverse functional properties, including having a potentially significant role in tumor development, and antibodies to CD26 mediate pleomorphic cellular functions. In this report, we show that binding of soluble anti-CD26 monoclonal Ab 1F7 inhibits the growth of the human CD30+ anaplastic large cell T-cell lymphoma cell line Karpas 299 in both in vitro and in vivo experiments. In vitro experiments show that 1F7 induces cell cycle arrest at the G1-S checkpoint, associated with enhanced p21 expression that is dependent on de novo protein synthesis. Furthermore, experiments with a severe combined immunodeficient mouse tumor model demonstrate that 1F7 treatment significantly enhances survival of tumor-bearing mice by inhibiting tumor formation. Our data therefore suggest that anti-CD26 treatment may have potential clinical use for CD26+ hematological malignancies.

Animals↗

Rapid quantitation of proinflammatory and chemoattractant cytokine expression in small tissue samples and monocyte-derived dendritic cells: validation of a new real-time RT-PCR technology.

The analysis of cytokine profiles plays a central part in the characterization of disease-related inflammatory pathways and the identification of functional properties of immune cell subpopulations. Because tissue biopsy samples are too small to allow the detection of cytokine protein, the detection of mRNA by RT-PCR analysis is often used to investigate the cytokine milieu in inflammatory lesions. RT-PCR itself is a qualitative method, indicating the presence or absence of specific transcripts. With the use of internal or external standards it may also serve as a quantitative method. The most widely accepted method is quantitative competitive RT-PCR, based on internal shortened standards. Recently, online real-time PCR has been introduced (LightCycler), which allows quantitation in less than 30 min. Here, we have tested its use for the analysis of cytokine gene expression in different experimental in vitro and ex vivo settings. First, we compared quantitative competitive RT-PCR with real-time RT-PCR in the quantitation of transcription levels of the CD4(+) cell-specific chemoattractant Interleukin-16 during the maturation of monocyte-derived dendritic cells, and found a good correlation between both methods. Second, differences in the amounts of IL-16 mRNA in synovial tissue from patients with rheumatoid arthritis and osteoarthritis as assessed by real-time RT-PCR paralleled differences in the level of IL-16 protein in the synovial fluid. Finally, we employed real-time RT-PCR to study the cutaneous expression of several cytokines during experimental immunomodulatory therapy of psoriasis by Interleukin-10, and demonstrate that the technique is suitable for pharmacogenomic monitoring. In summary, real-time RT-PCR is a sensitive and rapid tool for quantifying mRNA expression even with small quantities of tissue. The results obtained do not differ from those generated by quantitative competitive RT-PCR.

Arthritis, Rheumatoid↗

[The compartment syndrome--still a threat in traumatology].

Paper presents current opinions on the definition, causes, classification, diagnosis and treatment of the compartment syndrome (CS). The development of CS after the long-bone fractures of the lower extremity and also after the limb operations or trauma without fracture is discussed. The importance of early and correct diagnostics and treatment is also revealed. Authors present several case reports and they stress the importance of early fasciotomy when necessary.

Adult↗

NOAH--A mobile emergency care system.

Experiencing communication problems in our emergency services, we developed an innovative communication network and system the NOAH-system (NOAH, which stands for Notfall -, Organisations - und Arbeitshilfe or Emergency-Organisation Active Aide System). In contrast with the currently established emergency services communication in Germany by radio wave, data is transferred from the scene in the form of an electronic record on a mobile computer by means of the wireless data communication network Modacom (Mobile Data Communication), which is provided by German Telekom. It is received at the dispatch-centre in mentioned format and transferred to the admitting hospital without any loss of data. - In a prospective study, the technical and conceptual suitability of this system was investigated. It was shown that an admitting hospital was informed more than 20 minutes in advance about the admittance of a patient. To assure the quality of transferred data, information was ranked by different criteria. This further demonstrated that much more precise information about a patient's condition was already available upon admittance in the hospital.

Emergency Medical Services↗

T-cell clones from early-stage cutaneous T-cell lymphoma show no polarized Th-1 or Th-2 cytokine profile.

Recent studies of the cytokine pattern in skin lesions of patients with cutaneous T-cell lymphoma (CTCL) have shown that interleukin-4 (IL-4) and Il-10, both cytokines produced by T-helper type 2 cells, dominate in these lesions. Also, in single studies, interferon-gamma (IFN-gamma), a major cytokine of Th-1-cells, has been found to be absent. Consequently, it has been hypothesized that immune-suppressive Th-2 cytokines may promote local growth of the malignant lymphocyte clone. However, there is so far no evidence for T-cells as the source of the Th-2 cytokines in CTCL skin lesions nor have these cytokines been investigated at a clonal T-cell level. We established a total of 120 T-cell clones (TCCs) from lesional skin and 54 TCCs from the blood of four patients with mycosis fungoides. Epidermal TCCs (mostly CD8-positive) and dermal TCCs (mostly CD4-positive) were stimulated by the mitogen concanavalin A and, seeking a polarized cytokine pattern, the supernatants were assessed by ELISA. We showed that the vast majority of TCCs were able to secrete IFN-gamma and IL-4. IFN-gamma-deficient TCCs occurred only in the epidermis. Some (18) TCCs were found to be either negative for IL-10 production or to produce low levels only. No significant differences were observed between blood- and skin-derived TCCs. Thus a polarized Th-2 cytokine pattern was not detectable among cultured skin-infiltrating nonmalignant T-cells (TILs) isolated from early mycosis fungoides. It therefore appears unlikely that Th-2-mediated immune suppression is a major mechanism operating in early CTCL. However, this does not exclude its role in late-stage disease.

Aged↗

[Congenital manifestations of juvenile xanthogranuloma (large nodular form)].

An infant girl presented at birth with multiple, large nodular xanthogranulomas. Her monozygotic twin sister was not affected. The congenital tumors were up to 1.5 cm in diameter, done-shaped and mainly located on the head and the upper half of the body. Histologically the cells were characterized as CD68+ non-Langerhans histiocytes. Follow-up for 18 months showed no new tumors and regression of the existing ones. No extra-cutaneous manifestations were observed. Knowledge of the differential diagnosis, especially the group of Langerhans cell histiocytosis, is essential for prognosis estimation.

Biopsy↗

[Actinic prurigo].

The non-Native American type of actinic prurigo belongs to the group of rare idiopathic photodermatoses and therefore is often diagnosed with delay. The typical clinical and epidemiological features of actinic prurigo are described in a 10 year old girl. Detailed phototesting showed urticarial early onset and prurigo-like late onset reactions towards long-wave UVA. Repetitive photoprovocation with UVB induced delayed development of papules. HLA typing showed the typical association with HLA-DR4, in particular DRB1*0407. Treatment is usually extremely difficult and unrewarding. In this patient, the course was considerably improved by more intense physical photoprotection.

Antibodies, Antinuclear↗

Butyltins in shellfish, finfish, water and sediment from the Coos Bay estuary (Oregon, USA).

Butyltin was measured in tissue, water and sediment samples collected throughout Coos Bay estuary between 1986 and 1997. Butyltin-induced shell deformation in commercial oysters prompted this assessment. Butyltins are released from tributyltin oxide (TBTO)-containing boat paint. Clams from three sites contained tributyltin (TBT) levels ranging from 168 to 457 microg/kg in 1992-1994. Consequently, Oregon Health Division (OHD) issued a shellfish consumption advisory in 1995; it was rescinded in 1997 after US Environmental Protection Agency (EPA) revised the TBTO oral reference dose (RfD). The revised RfD changed the tissue screening level from 112 to 1120 microg TBT/kg. Fifty percent of sediment samples collected during 1991-1997 and analyzed for total butyltins (TotBT) exceeded the Puget Sound Dredge Disposal Analysis Screening Level (PSDDA SL) of 73 microg TBT/kg dw. TotBT at three shipyards selected for site assessment by EPA ranged from 24 to 68,613 microg/kg dw. Sediment and tissue butyltins have been decreasing in all but one area of the estuary.

Animals↗

A double-blind, crossover study of controlled-release metoclopramide and placebo for the chronic nausea and dyspepsia of advanced cancer.

To compare a novel controlled-release formulation of metoclopramide with placebo in patients with cancer-associated dyspepsia syndrome, 26 adult patients with a >/=1 month history of cancer-associated dyspepsia syndrome were randomized to receive either controlled-release metoclopramide 40 mg every 12 hours or matching placebo for a period of 4 days. On day 5, patients crossed over to the alternate treatment for a further period of 4 days. Dose adjustments and rescue antiemetics were permitted during both phases. Nausea, anorexia, bloating, vomiting/retching, and drowsiness were assessed on a 100-mm VAS scale in a daily diary. On the last day of treatment of each phase, nausea was significantly lower in the controlled-release metoclopramide group compared to placebo (17 +/- 12 mm versus 12 +/- 10 mm). Nausea scores tended to increase across days during the placebo phase and to decrease during the controlled-release metoclopramide phase. There was a trend for improvement in the intensity of all symptoms on controlled-release metoclopramide with the exception of appetite, but this trend only reached statistical significance for nausea. The frequency and severity of elicited adverse events did not differ significantly between treatments, although drowsiness, dizziness, and poor sleep were somewhat higher in the placebo group. In no case was it necessary to discontinue controlled-release metoclopramide because of toxicity. These results indicate that controlled-release metoclopramide reduces gastrointestinal symptoms in this population of advanced cancer patients.

Aged↗

Differences in immunoreactivity of estrogen receptor (ER) in tamoxifen-sensitive and -resistant breast carcinomas: preclinical and first clinical investigations.

Inherited or acquired tamoxifen resistance is a major constraint in the endocrinological treatment of breast carcinomas. We developed an enzyme-immunoassay that discriminates between tamoxifen-sensitive and -resistant tumors. The procedure was established and standardized using two xenografted breast carcinomas--3366 (highly sensitive to tamoxifen) and 3366/TAM (acquired tamoxifen resistance). The latter model was developed by treatment of 3366 tumor-bearing nude mice during serial passaging over 3 years with tamoxifen. Both lines were estrogen receptor (ER) positive (101 or 82 fmol/mg protein), and revealed no differences in the nucleotide sequences of the hormone binding domain of the ER protein. However, while in the sensitive tumors an upregulation of ER levels was registered after estradiol treatment of tumor bearing nude mice, the ER expression in the resistant line remained unchanged. The tamoxifen sensitive and -resistant breast carcinoma 3366 differed, additionally, in their immunoreactivity of ER to mAB H222. While an incubation with estradiol or tamoxifen of immobilized ER prepared from cytosols of the sensitive tumors 3366 led to a significant increase in immunoreactivity, samples of resistant tumors failed in the exposition of additional immunologically reactive epitopes. These results were the basis for the development of an assay for determination of the tamoxifen response in patients. Our retrospective results with 38 breast tumors from a tumor bank indicated that patients with an increase of immunoreactivity of ER more rarely had a recurrence while under going tamoxifen therapy compared with patients expecting no increase. However, the data indicate interesting changes occurring with the ER of tam-resistant tumors that are to be explained by further mutational or protein-chemical analysis.

Animals↗

N-acetyltransferase 1 and 2 polymorphisms in para-substituted arylamine-induced contact allergy.

Sensitization to arylamines such as p-phenylenediamine is frequently diagnosed in patients with allergic contact dermatitis. Reactive metabolites of p-phenylenediamine might be produced in the skin by O-acetylation of N-hydroxylamines catalysed by local N-acetyltransferases (NATs). In this study, we tested whether genetic polymorphisms of NATs, which are known to affect enzyme activity, may influence the susceptibility to para-substituted arylamine-induced contact eczema. Using polymerase chain reaction and restriction enzyme analysis, the distribution of polymorphisms of NAT1 and NAT2 was investigated in 88 patients sensitized to para-substituted aryl compounds and 123 healthy controls. NAT2 rapid acetylators, i.e. carriers of the NAT2*4 wild-type allele, were more common in the contact allergy (44%) than in the healthy control group [30%; P = 0.042, odds ratio 1.9 (95% confidence interval, CI 1. 05-3.27)]. Slow acetylators carrying the NAT2*5b/2*6a genotype were significantly less frequent among patients [13% vs. 38% in controls; P = 0.009, odds ratio 0.39 (95% CI 0.19-0.78)]. The carriage rate of the NAT1*10 allele, which is supposed to encode for a rapid NAT1 phenotype, was not significantly different between patients and controls [43% vs. 36%; odds ratio 1.5 (95% CI 0.88-2.68)]. Interactions between NAT2*4 and NAT1*10 were suggested by the increased frequency of the NAT2*4/NAT1*10 haplotype in patients (27%) compared with controls [15%; P = 0.039, odds ratio 2.1 (95% CI 1.04-4.04)]. As the NAT1 and NAT2 encoding genes are located in close proximity on chromosome 8p22, the latter finding could at least partly be due to genetic linkage. In fact, a linkage disequilibrium between NAT2*4 and NAT1*10 was observed in the contact allergy (P = 0.0025) and in the control group (P = 0.042). Our data indicate an association between the NAT2*4/NAT1*10 haplotype and contact sensitization to para-substituted aryl compounds. Therefore, acetylation may either enhance contact sensitization or NAT2*4 and NAT1*10 might be linked to an unknown susceptibility factor.

Adolescent↗

Impaired cutaneous permeability barrier function, skin hydration, and sphingomyelinase activity in keratin 10 deficient mice.

Point mutations in the suprabasal cytokeratins 1 (K1) or 10 (K10) in humans have been shown to be the cause of the congenital ichthyosis epidermolytic hyperkeratosis. Recently, a K10 deficient mouse model was established serving as a model for epidermolytic hyperkeratosis. Homozygotes suffered from severe skin fragility and died shortly after birth. Heterozygotes developed hyperkeratosis with age. To see whether phenotypic abnormalities in the mouse model were associated with changes in skin barrier function and skin water content we studied basal transepidermal water loss and capacity for barrier repair after experimental barrier disruption as well as stratum corneum hydration. Also, we determined the activities of acid and neutral sphingomyelinase key enzymes of the tumor necrosis factor and interleukin-1 signal transduction pathways generating the ceramides most important for epidermal permeability barrier homeostasis. Neonatal homozygotes showed an 8-fold increase in basal transepidermal water loss compared with wild type controls. Adult heterozygotes exhibited delayed barrier repair after experimental barrier disruption. Stratum corneum hydration was reduced in homozygous and heterozygous mice. Acid sphingomyelinase activity, which is localized in the epidermal lamellar bodies and generates ceramides for extracellular lipid lamellae in the stratum corneum permeability barrier, was reduced in homozygous as well as heterozygous animals. Neutral sphingomyelinase activity, which has a different location and generates ceramides involved in cell signaling, was increased. The reduction in acid sphingomyelinase activity may explain the recently described decreased ratio of ceramides to total lipids in K10 deficient mice. In summary, our results demonstrate the crucial role of the keratin filament for permeability barrier function and stratum corneum hydration.

Animals↗

Development and characterization of a tamoxifen-resistant breast carcinoma xenograft.

A human tamoxifen-resistant mammary carcinoma, MaCa 3366/TAM, originating from a sensitive parental xenograft 3366 was successfully established by treatment of tumour-bearing nude mice with 1-50 mg kg(-1) tamoxifen for 3 years during routine passaging. Both tumours did not differ significantly in OR- and PR-positivity, however, when compared with the sensitive tumour line, the mean OR content of the TAM-resistant subline is slightly lower. An OR-upregulation following withdrawal of oestradiol treatment was observed in the parental tumours but not in the resistant xenografts. Following long-term treatment with tamoxifen, the histological pattern of the breast carcinoma changed. The more differentiated structures being apparent after treatment with 17beta-oestradiol in the original 3366 tumour were not induced in the resistant line. Tamoxifen failed to induce a tumour growth inhibition in comparison to the tamoxifen-sensitive line. The pure anti-oestrogen, ICI 182 780, revealed cross-resistance. Sequence analysis of the hormone-binding domain of the OR of both lines showed no differences, suggesting that either mutations in other regions of the OR are involved in the TAM-resistance phenotype or that mechanisms outside of this protein induced this phenotype. Oestrogen and anti-oestrogen regulate pS2 and cathepsin D expression in 3366 tumours as in the human breast cancer cell line MCF-7. The resistant 3366/TAM tumours have lost this regulation. The established breast cancer xenografts 3366 and 3366/TAM offer the possibility of investigating mechanisms of anti-oestrogen resistance in an in vivo situation. They can be used to test novel approaches to prevent, or to overcome, this resistance in a clinically related manner.

Animals↗

Prognostic factors of overall survival in patients with delayed lymph node dissection for cutaneous malignant melanoma.

To date, no study of melanoma patients who have undergone delayed lymph node dissection (DLND) has focused on the independent prognostic factors of overall survival, as calculated from surgery on the primary. Using Kaplan-Meier estimates and Cox's proportional hazard model, the significance of prognostic factors was evaluated in 173 patients who developed clinically apparent regional lymph node metastases. When calculated from excision of the primary tumour (median Breslow thickness 3.0 mm), the median survival was 38 months. When calculated from DLND, the median survival was 19 months. Multifactorial analysis revealed that the number of nodes involved at the time of DLND significantly affected both survival calculated from primary tumour excision (P = 0.0002) and survival calculated from DLND (P < 0.0001). In contrast, the well-known risk factors of primary melanoma did not significantly influence overall survival or survival after DLND. However, the remission duration between surgery on the primary and DLND clearly depended on epidermal ulceration (P = 0.001), Breslow thickness (P = 0.009) and the site of the primary melanoma (P = 0.048). Thus, in patients submitted to DLND, the risk factors of primary melanoma influence the early period of the disease, until metastatic lymph nodes become palpable. With regard to overall survival, only the extent of nodal disease determines the prognosis of these patients.

Antineoplastic Combined Chemotherapy Protocols↗