Isolation of human monocytes by ficoll density gradient centrifugation

Summary The separation of human blood monocytes by a two step density gradient centrifugation using Ficoll is reported. From 10 ml venous blood 0.5×10⁶ monocytes could be harvested with a purity of 72 ± 11%. Cells characteristics typical of monocytes (positive -naphthylesterase staining, phagocytosis of polyacrylic acid beads, antigen presenting, adherence on plastic surfaces) confirmed the identity and the intact function of these cells.Supported by the Stiftung Volkswagenwerk (Az I 35 229)     

Transformation of MALT lymphoma to pure plasma cell histology following treatment with the anti-CD20 antibody rituximab

Mucosa associated lymphoid tissue (MALT) lymphoma is a relatively common lymphoma arising from marginal-zone B-cells which are closely related to plasma cells. As opposed to the large majority of plasma cells, MALT lymphoma cells express CD20, and the anti-CD20 antibody rituximab has been reported as active treatment in patients with MALT lymphoma. We present a patient with MALT lymphoma involving stomach and lung which transformed to a pure plasma cell tumor after therapy with rituximab. This observation again supports the close association between the cell of origin of MALT lymphoma and plasma cells, suggesting that “plasmacytoma of the GI-tract” as anecdotally reported may in fact be a MALT lymphoma with extreme plasmacytic differentiation. In addition, our findings suggest that MALT lymphomas with plasmacytic differentiation might have a different 18F-FDG uptake as compared to classical MALT lymphoma.     

Morphology of tumor cell nuclei is significantly related with survival time of patients with glioblastomas.

PURPOSE: To investigate whether histomorphology of tumor cell nuclei has a significant and independent relation to survival time of patients with glioblastomas. EXPERIMENTAL DESIGN: Seventy-two tumors from 72 patients were investigated by means of digital image analysis. Proliferating and nonproliferating nuclei were separately measured and parameters of nuclear size, shape, texture, and spatial relationships (topometric parameters) were detected. Survival analysis was done regarding morphometric data together with the patients' age, the amount of resection (total or subtotal), and the classification of the tumor as a "primary" (de novo) or "secondary" glioblastoma. RESULTS: The overall relation of all morphometric data to the time of survival was highly significant (Cox analysis, P < 0.0001). Apart from the extent of surgical resection, parameters of nuclear shape and topometric variables, such as the distance between two nuclei lying nearest to each other, showed an independent and significant relation to survival time. The patients' age had also a significant but comparably slight relation to survival time. CONCLUSIONS: The morphology of tumor cell nuclei, as represented by morphometric data, shows a significant relation to survival time of patients with glioblastomas. This relation is statistically independent from the amount of surgical resection, from the patients' age and from the classification of the glioblastoma as being primary or secondary. The results support the view that histomorphometry of tumor cell nuclei is a valuable prognostic marker for patients with glioblastomas. We believe that such a marker ought to be incorporated into the formation of individual therapeutic decisions.     

Microarray versus conventional prediction of lymph node metastasis in colorectal carcinoma

BACKGROUND: The authors investigated whether microarray-based gene expression analysis of primary tumor biopsy material could be used to predict lymph node status in patients with colorectal carcinoma (CRC). Lymphatic metastasis strongly determines treatment algorithms in CRC. Currently, postoperative histology results are needed to determine lymph node status. Reliable preoperative information would be useful to advance treatment strategies. METHODS: In specimens from 66 patients with CRC from the Erlangen Registry of Colorectal Cancer, 41 shock-frozen samples of International Union Against Cancer (UICC) Stage I-II CRC and 25 samples of UICC Stage III CRC were microdissected manually, RNA was isolated, and gene chips (HG-U133A; Affymetrix) were hybridized. Prediction rates for lymphatic metastasis were calculated using conventional clinicopathologic parameters, gene expression data, and a combination of both. Prediction error, specificity, and sensitivity were analyzed using six different statistical classifiers. RESULTS: Analysis of conventional parameters produced a positive prediction rate that ranged between 53% and 61%, sensitivity of 42%, and specificity of 72%. Microarray prediction rates were between 62% and 67% for lymphatic metastasis. Specificity was between 76% and 83%, and sensitivity was between 38% and 48%, depending on the statistical procedure. The conventional estimates were improved by 9-12% when array data were added. CONCLUSIONS: Current data show that the prediction of lymphatic metastasis can be improved by gene expression profiling of the primary tumor biopsy, alone or in combination with conventional parameters. Gene expression profiling may become valuable increasingly in planning treatment for patients with CRC.     

Neuroendocrine stress response and heart rate variability: a comparison of total intravenous versus balanced anesthesia

Attenuating intraoperative stress is a key factor in improving outcome. We compared neuroendocrine changes and heart rate variability (HRV) during balanced anesthesia (BAL) versus total IV anesthesia (TIVA). Forty-three patients randomly received either BAL (sevoflurane/remifentanil) or TIVA (propofol/remifentanil). Depth of anesthesia was monitored by bispectral index. Stress hormones were measured at 7 time points (P1 = baseline; P2 = tracheal intubation; P3 = skin incision; P4 = maximum operative trauma; P5 = end of surgery; P6 = tracheal extubation; P7 = 15 min after tracheal extubation). HRV was analyzed by power spectrum analysis: very low frequency (VLF), low frequency (LF), high frequency (HF), LF/HF ratio, and total power (TP). LF/HF was higher in TIVA at P6 and TP was higher in TIVA at P3-7 (P3: 412.6 versus 94.2; P4: 266.7 versus 114.6; P5: 290.3 versus 111.9; P6: 1523.7 versus 658.1; P7: 1225.6 versus 342.6 ms2)). BAL showed higher levels of epinephrine (P7: 100.5 versus 54 pg/mL), norepinephrine (P3: 221 versus 119.5; P4: 194 versus 130.5 pg/mL), adrenocorticotropic hormone (P2 10.5 versus 7.7; P5: 5.3 versus 3.6; P6: 10.9 versus 5.3; P7: 20.5 versus 7.1 pg/mL) and cortisol (P7: 6.9 versus 3.9 microg/dL). This indicates a higher sympathetic outflow using BAL versus TIVA during ear-nose-throat surgery.     

Immunosuppressive therapy with everolimus can be associated with potentially life-threatening lingual angioedema

Everolimus has recently received approval for immunosuppressive therapy in heart transplant recipients in Austria and Germany. At our heart center we have treated 114 patients with everolimus since January 2004. Here we describe 6 cases of lingual angioedema (corresponding to 5.3% of the patients). Symptoms occurred within 2 to 41 days after initiation of therapy. In 5 out of the 6 patients, lingual angioedema disappeared with anti-allergic treatment alone. However, in one patient, two severe recurrent episodes of lingual angioedema occurred so that therapy had to be discontinued. We conclude that the potentially life-threatening condition of lingual angioedema should be considered a severe drug reaction after initiation of everolimus therapy in heart transplant recipients.     

Disaster-related posttraumatic stress symptoms and sustained attention: evaluation of depressive symptomatology and sleep disturbances as mediators

Research about attentional functioning following trauma has almost exclusively been performed in patient populations with combat-related posttraumatic stress disorder (PTSD). In this study the relationship between sustained attention and PTSD symptoms was examined in a community sample of survivors of a major disaster using the Paced Auditory Serial Addition Task (PASAT) and the Self-Rating Scale for PTSD (SRS-PTSD) 2-3 years postdisaster. Analyses revealed low but significant partial correlations between PTSD symptoms and the least difficult subtests, ruling out the effects of age, education, depressive symptomatology, and sleep disturbances. These results demonstrate that PTSD symptoms link to attentional dysfunction 2-3 years postdisaster.     

Mental health of Cambodian refugees 2 decades after resettlement in the United States

Context  Little is known about the long-term mental health of trauma-exposed refugees years after permanent resettlement in host countries. Objective  To assess the prevalence, comorbidity, and correlates of psychiatric disorders in the US Cambodian refugee community. Design, Setting, and Participants  A cross-sectional, face-to-face interview conducted in Khmer language on a random sample of households from the Cambodian community in Long Beach, Calif, the largest such community in the United States, between October 2003 and February 2005. A total of 586 adults aged 35 to 75 years who lived in Cambodia during the Khmer Rouge reign and immigrated to the United States prior to 1993 were selected. One eligible individual was randomly sampled from each household, with an overall response rate (eligibility screening and interview) of 87% (n = 490). Main Outcome Measures  Exposure to trauma and violence before and after immigration (using the Harvard Trauma Questionnaire and Survey of Exposure to Community Violence); weighted past-year prevalence rates of posttraumatic stress disorder (PTSD) and major depression (using the Composite International Diagnostic Interview version 2.1); and alcohol use disorder (by the Alcohol Use Disorders Identification Test). Results  All participants had been exposed to trauma before immigration. Ninety-nine percent (n = 483) experienced near-death due to starvation and 90% (n = 437) had a family member or friend murdered. Seventy percent (n = 338) reported exposure to violence after settlement in the United States. High rates of PTSD (62%, weighted), major depression (51%, weighted), and low rates of alcohol use disorder were found (4%, weighted). PTSD and major depression were highly comorbid in this population (n = 209; 42%, weighted) and each showed a strong dose-response relationship with measures of traumatic exposure. In bivariate analyses, older age, having poor English-speaking proficiency, unemployment, being retired or disabled, and living in poverty were also associated with higher rates of PTSD and major depression. Following multivariate analyses, premigration trauma remained associated with PTSD (odds ratio [OR], 2.08; 95% CI, 1.37-3.16) and major depression (OR, 1.56; 95% CI, 1.24-1.97); postmigration trauma with PTSD (OR, 1.65; 95% CI, 1.21-2.26) and major depression (OR, 1.45; 95% CI, 1.12-1.86); and older age with PTSD (OR, 1.76; 95% CI, 1.46-2.13) and major depression (OR, 1.47; 95% CI, 1.15-1.89). Conclusion  More than 2 decades have passed since the end of the Cambodian civil war and the subsequent resettlement of refugees in the United States; however, this population continues to have high rates of psychiatric disorders associated with trauma.      

Overlapping induction of anesthesia: an analysis of benefits and costs

BACKGROUND: Overlapping induction (OI), i.e., induction of anesthesia with an additional team while the previous patient is still in the operating room (OR), was investigated. METHODS: The study period was 60 days in two followed by three ORs during surgical Block Time (7:30 am until 3:00 pm). Patients were admitted the day before surgery and were thus available and did not have surgery that day unless there was a time reduction. Facilities were already constructed. Number of cases, Nonsurgical Time (Skin Suture Finish until next Procedure Start Time), Turnover Time, and Anesthesia Control Time plus Turnover Time were studied. In addition, economic benefit was calculated. RESULTS: Three hundred thirty-five cases were studied. Using OI, the time of care of regularly scheduled cases was shortened, and the number of cases performed within OR Block Time increased (151 to 184 cases; P < 0.05). Nonsurgical Time (in h:min) decreased (1:08 +/- 0:26 to 0:57 +/- 0:18; P < 0.001), Turnover Time decreased (0:38 +/- 0:24 to 0:25 +/- 0:15; P < 0.05), and Anesthesia Control Time plus Turnover Time decreased (0:43 +/- 0:23 to 0:28 +/- 0:18; P < 0.001). Subgroup analysis showed a significant benefit of OI only in three ORs. In three ORs, economic benefit can be gained at a case mix index greater than 0.3 besides additional costs. CONCLUSIONS: Overlapping induction increased productivity and profit despite the expense of additional staff. Subgroup analysis emphasizes the importance of the number of ORs involved in OI.