Biophysicochemical Interaction of a Clinical Pulmonary Surfactant with Nanoalumina.

We report on the interaction of pulmonary surfactant composed of phospholipids and proteins with nanometric alumina (Al2O3) in the context of lung exposure and nanotoxicity. We study the bulk properties of phospholipid/nanoparticle dispersions and determine the nature of their interactions. The clinical surfactant Curosurf, both native and extruded, and a protein-free surfactant are investigated. The phase behavior of mixed surfactant/particle dispersions was determined by optical and electron microscopy, light scattering, and zeta potential measurements. It exhibits broad similarities with that of strongly interacting nanosystems such as polymers, proteins or particles, and supports the hypothesis of electrostatic complexation. At a critical stoichiometry, micron-sized aggregates arising from the association between oppositely charged vesicles and nanoparticles are formed. Contrary to the models of lipoprotein corona or of particle wrapping, our work shows that vesicles maintain their structural integrity and trap the particles at their surfaces. The agglomeration of particles in surfactant phase is a phenomenon of importance that could change the interactions of the particles with lung cells.

Frequency of comorbid illnesses in cancer patients in Turkey.

PURPOSE: Comorbidities in cancer patients can adversely affect the management and outcome of their primary illnesses at all levels from diagnosis to therapy. We sought to examine comorbid conditions of cancer patients, treated at 4 university hospitals, each representing a different geographic location in Turkey. METHODS: A total of 769 consecutive cancer patients presenting to outpatient clinics were recruited between November 2007 and May 2008. The patients filled in a questionnaire on comorbidities. Based on the questionnaire, Charlson Comorbidity Index (CCI( was calculated. RESULTS: The patient median age was 55 years (range 21-87) and 456 (59.3%) were female. Breast (36.5%), colorectal (21.4%) and lung cancers (13.9%) were the 3 most frequent malignancies. Of the patients, 59.3% had at least one comorbid disease and 46.3% were using at least one medication daily. The most frequent comorbidities were hypertension (25.3%), diabetes mellitus (13.1%) and peptic ulcer (7.7%). Increasing age positively correlated with the extent of comorbidities (r=0.30, p<0.001), number of medications (r=0.32, p<0.001) and the CCI (r=0.20, p<0.001). CONCLUSION: It is crucial to remember that comorbid illnesses are not rare and many patients are treated for conditions unrelated to their cancer, which potentially may affect various stages of their clinical management.

Signet ring cell carcinoma of the breast as a source of pelvic floor metastatic mass. A case report.

Primary signet ring cell carcinoma of the breast is a very rare tumour. We present a case with pure signet ring cell carcinoma of the breast, which was recognized as metastasis on the pelvic floor, before developing breast symptoms and signs. A 40-year old woman was admitted with abdominal pain. First diagnostic effort revealed a cystic mass on the pelvic floor, compressing the colon and other neighbouring organs. A biopsy of the pelvic mass was performed. The histopathological examination revealed metastatic signet-ring cell carcinoma. At the time of the first operation, the mammary glands were not suspicious. No other sources of primary tumour were evidenced. An inflammatory sign developed in right breast two months after biopsy of the pelvic metastasis. The histopathology of the breast incisional biopsy revealed primary pure signet ring cell carcinoma of the breast. Because the oestrogen and progesterone receptor were negative in the tumoral tissue, the patient underwent chemotherapy followed by modified radical mastectomy, chemotherapy, and palliative resection of the metastatic mass. The patient was followed up for eight months. To our knowledge, in English literature, we believe that this case is the first report of signet ring cell carcinoma of the breast presenting with pelvic floor metastasis without breast sign.

Prognostic value of matrix metalloproteinases (MMP-2 and MMP-9) in Hodgkin's and non-Hodgkin's lymphoma.

Matrix metalloproteinases (MMPs) are responsible for the degradation of extracellular matrix and have an important role in tumour metastases. We investigated the role of MMP-2 and MMP-9 in Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). The serum samples of patients with HD (n = 12), NHL (n = 30) and healthy control (n = 22) were analysed for MMP-2 and MMP-9. An immunoassay method was used for the determination of MMP-2 and MMP-9 levels. No statistical significance was found between HD and NHL groups for levels of MMP-2. There were no relation between MMP-2, MMP-9 levels and clinical characteristics of patients. The mean MMP-9 levels were found to be 555.6 +/- 140 ng/ml, 446.6 +/- 53.6 ng/ml and 111.2 +/- 10.3 ng/ml in HD, NHL and control groups, respectively. Our results suggest that MMP-9 levels are substantially increased in HD and NHL when compared with controls and may probably be used for distinguishing the benign diseases from malign lymphomas.

High-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous stem cell transplantation in patients with advanced breast cancer: a retrospective evaluation.

This study was conducted to evaluate the efficacy of high-dose thiotepa, melphalan and carboplatin (TMCb) regimen in 27 patients undergoing autologous stem cell transplantation (ASCT) for metastatic breast cancer. A total of 27 patients with stage IV breast cancer underwent ASCT following thiotepa (500 mg/m(2)), melphalan (100 mg/m(2)) and carboplatin (1200-1350 mg/m(2)). Of 27 patients, 17 had refractory relapse, eight had responding relapse, and two had no evidence of disease (NED) at the time of transplant. In all, 11 patients had only bone disease, nine had bone plus visceral disease, three had only visceral disease, and two had locoregional recurrent disease. The median time from diagnosis to transplant was 1081 days (range 180-2341). Staging for evaluation of response was performed 4-6 months after transplantation. Five patients were not evaluable (NE) for response because of NED at transplant (n=2) or early death due to transplant-related complications (n=3) (two of viral pneumonia and one of regimen-related toxicity) occurring at a median of 4 days (range 11-46) post-transplant. One of the two patients who was NED at the time of transplant is still NED on day 760 post-transplant. Seven of 15 refractory (47%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft-tissue disease with at least improvement in bone lesions. Of 27 patients (37%),(10) are alive and progression-free, a median of 582 days (range 410-1380) after treatment, 6/17 (35%) with refractory disease and 4/10 (40%) with responsive disease. The probability of progression-free survival (PFS) for all patients was 0.50. The probabilities of PFS at 2 years for patients with refractory (n=17) and responsive (n=10) disease were 0.42 and 0.60, respectively. PFS at 2 years for the 14 patients who were NED or achieved CR/PR(*) following-HDC was 0.67. PFS at 2 years for patients who did not achieve CR/PR(*) following-DHC was 0.33. These preliminary data suggest that high-dose TMCb followed by autologous stem cell transplantation is an effective regimen for patients with advanced breast cancer and may be comparable to some previously used regimens.

A randomized trial of assessment of efficacy of leukapheresis volumes, 8 liters vs 12 liters.

It is logical to expect that large-volume leukapheresis may be able to collect adequate numbers of PBSC with fewer procedures. To date, there is no agreement on the optimal volume of leukapheresis. Therefore, in this study we compared 8 l volume with 12 l and assessed whether a 50% increase in the blood volume processed would decrease the number of leukaphereses each patient needed to collect > or =2.5 x 10(6) CD34(+) cells/kg in normal mobilizers. PBSC mobilization was done with cyclophosphamide etoposide followed by rhG-CSF in all patients. Forty patients were randomized to undergo 8 l leukaphereses (n = 20 patients) or 12 l leukaphereses (n = 20). The median numbers of leukaphereses required in order to collect > or =2.5 x 10(6) CD34(+) cells/kg in patients processed with 8 l and 12 l were 1 (range 1-5) and 1 (1-4), respectively (P = 0.50). The median number of total nucleated cells (TNC) collected per patient was greater for the 12 l group (7.47 x 10(8)/kg vs 3.90 x 10(8)/kg, P < 0.001), as was the median number of total mononuclear cells (TMNC) (4.26 x 10(8)/kg vs 2.16 x 10(8)/kg, P < 0.001), whereas there was no difference between the two groups for the median number of CD34(+)cells collected per patient (8.94 x 10(6)/kg vs 8.60 x 10(6)/kg, P = 0.85). The TNCs and TMNCs collected per leukapheresis were again greater for the 12 l group (3.64 x 10(8)/kg vs 1.91 x 10(8)/kg, P = 0.001 and 2.17 x 10(8)/kg vs 0.88 x 10(8)/kg, P < 0.001), whereas there was no difference between the two groups for the median number of CD34(+) cells collected per leukapheresis (3.98 x 10(6)/kg vs 3.26 x 10(6)/kg, P = 0.90). This study showed that there is no difference between 8 l and 12 l volumes in regard to collected CD34(+) cells/kg and also the use of a 12 l leukapheresis volume did not decrease the number of leukaphereses performed compared with a 8 l leukapheresis volume. In fact, the use of the larger leukapheresis volume had the disadvantage of adding 60 min to the time the patient was on the machine.

Binding of bovine serum albumin to heparin determined by turbidimetric titration and frontal analysis continuous capillary electrophoresis.

The association of proteins with glycosaminoglycans is a subject of growing interest, but few techniques exist for elucidating this interaction quantitatively. Here we demonstrate the application of capillary electrophoresis to the system of serum albumin (SA) and heparin (Hp). These two species form soluble complexes, the interaction increasing with reduction in pH and/or ionic strength (I). The acid-base property of Hp was characterized by potentiometric titration of ion-exchanged Hp. Conditions for complex formation with SA were qualitatively determined by turbidimetry, which revealed points of incipient binding (pH(c)) and phase separation (pH(phi)), both of which depend on I. At pH > pH(phi), i.e., prior to phase separation, frontal analysis continuous capillary electrophoresis was used to measure the concentration of free protein and to determine the protein-HP binding isotherm. The binding isotherms were well fit by the McGhee-von Hippel model to yield quantitative binding information in the form of intrinsic binding constants (K(obs)) and binding site size (n). The strong increase in K(obs) with decrease of pH or I could be explained on the basis of electrostatic interactions, considering the effects of protein charge heterogeneity. The value of n, independent of pH, was rationalized on the basis of size considerations. The implications of these findings for clinical applications of Hp and for its physiological behavior are discussed.

Refractory breast cancer: a comparison of two different chemotherapy regimens.

Sixty metastatic and recurrent breast cancer patients who had been given cyclophosphamide, methotrexate and fluorouracil (CMF) therapy previously and were treated at the Oncology Departments of Cukurova and Ege University Medical Schools between March 1992-94, were randomized into 2 groups for the chemotherapy program. The 30 patients in the 1st group were given etoposide: 200 mg x day x 5 days orally every 3 weeks. The 30 patients of the 2nd group were given fluorouracil: 500 mg x m2, doxorubicin: 5O mg/m2, cyclophosphamide: 500 mg/m2 intravenously every 3 weeks. The response rates were 21/30 in group 1 and 17/30 in group 2. The median duration of responses was 11 months (8-21) in the 1st and 9 months (4-18) in the 2nd group. Severe myelotoxicity was observed in 2 of the patients in the 1st group and in 5 of the patients in the 2nd group.

The use of recombinant human granulocyte colony-stimulating factor in combination with single or fractionated doses of ifosfamide and doxorubicin in patients with advanced soft tissue sarcoma.

Sixty patients with stage III-B and IV soft tissue sarcomas were randomized to receive either ifosfamide 5 g/m2xdx1 and doxorubicin 60 mg/m2xdx1 given every 3 weeks (arm A) or ifosfamide 1.8 g/m2xdx5 and doxorubicin 60 mg/m2xdx1 given every 4 weeks (arm B). Recombinant human granulocyte colony-stimulating factor (r-met Hu G-CSF: 250 micrograms/m2xd) was applied with a prophylactic intent to patients in arm A only. The response rate was higher in arm A patients (56% versus 33%, p = 0.03). In stage III patients, the complete response rate was significantly higher (53% versus, 13.3%, p = 0.01) and the duration of response was significantly longer in arm A (20 +/- 8.2 months versus, 13.4 +/- 7 months, p = 0.05). Chemotherapy related myelotoxicity and mucositis were also less frequent in this arm as a result of prophylactic r-met Hu G-CSF administration (p = 0.04, p = 0.003). It was concluded that single dose ifosfamide and doxorubicin combinations deserve further investigation under the cover of hematopoietic growth factors, particularly in patients with stage III soft tissue sarcomas.

Intracellular glutathione content in leukemias.

The intracellular glutathione (GSH) content was measured in 73 patients with leukemia and compared with controls. GSH content was between 1.16 and 5.55 mumol/g protein (mean 2.96 +/- 0.86) in the study group and between 0.5 and 1.48 mumol/g protein (mean 1.31 +/- 0.27) in the control group, statistically significant difference (p = 0.0000). There was no significant difference between acute and chronic leukemias, lymphoid and myeloid leukemias and, more importantly, newly diagnosed and relapsed patients. GSH content did not change significantly with clinical and hematologic parameters such as age, sex, and initial hematologic findings. In addition, variable changes were detected over 24 h in 9 patients. It can be concluded that GSH content in leukemic cells was higher than in controls and showed a wide range. The absence of a relationship between GSH content and clinical and laboratory parameters suggested that GSH is not the sole determinant of response to cytotoxic drugs. GSH variation over a 24-hour period may be important in the timing and success of chemotherapy for leukemias.

Serum levels of tumor necrosis factor in squamous cell carcinoma of the head and neck.

PURPOSE: Tumor necrosis factor (TNF)-alpha is a multifunctional cytokine that influences the clinical outcome in a number of diseases. This study was undertaken to evaluate its role in the differential diagnosis of malignant and benign tumors and in the follow-up of patients. We also studied the correlation of TNF-alpha levels with the stage and differentiation of the diseases. METHODS: In this study, serum levels of TNF-alpha are determined by the immunoradiometric assay method in 26 patients with head and neck cancer, and results are compared with 8 control patients with benign diseases. In both groups, serum samples were taken before and after the therapy. After centrifugation, the sera was stored at -70 degrees C until analyzed. TNF-alpha levels were measured by TNF-alpha immunoradiometric assay (IRMA) kit (Medgenix, Diagnostics SA, Belgium). RESULTS: The pretreatment mean value of TNF-alpha in the study group (814.1 pg/mL) was almost 100 times higher than in the control group (8.6 pg/mL) (P = .001). It was also noted that posttreatment mean value (94 pg/mL) was significantly lower than pretreatment mean value in the study group (P = .001). No statistically significant difference was found between serum TNF-alpha levels and the stage and differentiation of the tumor. CONCLUSION: The serum levels of TNF-alpha may be an efficient tumor marker in the diagnosis of patients with head and neck cancer.

Sweet's syndrome associated with G-CSF.

Sweet's syndrome (SS) developed in two patients with acute myeloid leukaemia (AML) treated with granulocyte colony stimulating factor (G-CSF) for febrile neutropenia due to AML chemotherapy. Fever, painful skin and conjunctival lesions developed and neutrophilic infiltration was detected at biopsy specimens. Neutrophilia was not detected. Skin lesions regressed within 1-2 weeks and conjunctival lesions within 4 weeks following the cessation of G-CSF. We conclude that SS may be a complication of G-CSF therapy and tender skin and/or conjunctival lesions developing during G-CSF therapy should suggest the possibility of SS.

Is there any relationship between pica and liver failure?

Pica is defined as the compulsive eating of anything and has been known for more than a hundred years. It is a worldwide problem which can be seen in every race, age, sex and geographic region. Its true incidence is not known and may be greater than expected. Although it is a widespread phenomenon, the causes and risk factors of pica are not well established. Clinical signs and symptoms of pica syndrome are numerous but liver disorder associated with this syndrome is not widely reported. We reported here liver disorder possibly related with pica.