Intra-arterial chemotherapy with mitomycin C in gallbladder cancer: a follow-up study

BACKGROUND AND OBJECTIVES: There is only limited and somewhat controversial information available on hepatic artery infusion of cytotoxic agents in gallbladder cancer. We report the results of 5-year follow-up of all gallbladder cancer patients treated with surgery and intra-arterial mitomycin C or mitomycin C alone in our hospital during 15 years. METHODS: Thirty-five patients with gallbladder cancer were treated with superselective intra-arterial chemotherapy (SIAC) with mitomycin C during 1981-1996. Survival was measured from diagnosis, and all patients were followed up until death or the end of January 2002. Cumulative survival rates and median survival times were calculated for all patients, according to response to treatment and staging. The data are presented as 5-year survival. RESULTS: Median survival times after SIAC for all patients, responders, and non-responders were 48, 60+, and 8.5 months, respectively. Overall response rate was 60%. Survival was significantly better for tumors limited to the gallbladder wall, as expected. Drug toxicity occurred in half of the patients, requiring cessation of chemotherapy in 25% of the cases. CONCLUSIONS: The median survival of gallbladder cancer patients treated with surgery and SIAC seems to be significantly better compared to the previously reported outcome of surgical treatment alone. Drug toxicity limits the use of i.a. chemotherapy and requires careful monitoring for early side-effects.     

Pharmacological characterization of ligand-receptor interactions at the zebrafish bradykinin receptor

Ligand interactions of a piscine bradykinin (BK) receptor expressed in vitro have been characterized for the first time by measuring inositol phosphate accumulation.The ligands were analogues of zebrafish BK with serial substitutions by D-amino acids or alanine. Substitutions at residues Arg(1), Gly(4), Ser(6), Pro(7), Leu(8) and Arg(9) caused greatly reduced potency and maximum response. The Pro(3) --> Ala analogue had higher potency but lower maximum response.The peptide HOE140 was a weak partial agonist although it is an antagonist at the human B2 receptor and a potent agonist at chicken B2.Thus, cloned zebrafish BK receptor reveals a ligand-interaction profile that is distinct from mammalian B1 and B2 receptors and from the previously characterized BK receptor in trout stomach, but similar to the receptor in cod intestine. These results increase our understanding of the evolution of BK receptors and the functions of the kallikrein-kinin system.     

Long-term results of surgery for lumbar spinal stenosis: a randomised controlled trial

We randomised a total of 94 patients with long-standing moderate lumbar spinal stenosis (LSS) into a surgical group and a non-operative group, with 50 and 44 patients, respectively. The operative treatment comprised undercutting laminectomy of stenotic segments, augmented with transpedicular-instrumented fusion in suspected lumbar instability. The primary outcome was the Oswestry disability index (ODI), and the other main outcomes included assessments of leg and back pain and self-reported walking ability, all based on questionnaire data from 85 patients at the 6-year follow-up. At the 6-year follow-up, the mean difference in ODI in favour of surgery was 9.5 (95% confidence interval 0.9–18.1, P-value for global difference 0.006), whereas the intensity of leg or back pain did not differ between the two treatment groups any longer. Walking ability did not differ between the treatment groups at any time. Decompressive surgery of LSS provided modest but consistent improvement in functional ability, surpassing that obtained after non-operative measures.     

Quantification of vesicles in differentiating human SH-SY5Y neuroblastoma cells by automated image analysis

A new automated image analysis method for quantification of fluorescent dots is presented. This method facilitates counting the number of fluorescent puncta in specific locations of individual cells and also enables estimation of the number of cells by detecting the labeled nuclei. The method is here used for counting the AM1-43 labeled fluorescent puncta in human SH-SY5Y neuroblastoma cells induced to differentiate with all-trans retinoic acid (RA), and further stimulated with high potassium (K+) containing solution. The automated quantification results correlate well with the results obtained manually through visual inspection. The manual method has the disadvantage of being slow, labor-intensive, and subjective, and the results may not be reproducible even in the intra-observer case. The automated method, however, has the advantage of allowing fast quantification with explicitly defined methods, with no user intervention. This ensures objectivity of the quantification. In addition to the number of fluorescent dots, further development of the method allows its use for quantification of several other parameters, such as intensity, size, and shape of the puncta, that are difficult to quantify manually.     

EEG/(f)MRI measurements at 7 Tesla using a new EEG cap ("InkCap")

We aimed at improving the signal-to-noise ratio (SNR) of electroencephalography (EEG) during magnetic resonance imaging (MRI) by introducing a new EEG cap ("InkCap") based on conductive ink technology. The InkCap was tested with temperature measurements on an electrically conductive phantom head and during structural and functional MRI (fMRI) recordings in 11 healthy human volunteers at 7 T. Combined EEG/fMRI measurements were conducted to study the interaction between the two modalities. The EEG recordings with the InkCap demonstrated up to a five-fold average decrease in signal variance during echo-planar imaging, with respect to a cap made of standard carbon fiber leads. During concurrent EEG/fMRI measurements in human volunteers, alpha oscillations were clearly detected at 7 T. Minimal artifacts were present in the T2* and high-resolution structural MR images of the brain parenchyma. Our results show that the InkCap technology considerably improves the quality of both EEG and (f)MRI during concurrent measurements even at 7 T.     

SuPAR and PAI-1 in critically ill, mechanically ventilated patients

Purpose

SuPAR (soluble urokinase plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1) are active in the coagulation-fibrinolysis pathway. Both have been suggested as biomarkers for disease severity. We evaluated them in prediction of mortality, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sepsis and renal replacement therapy (RRT) in operative and non-operative ventilated patients.

Methods

We conducted a prospective, multicenter, observational study. Blood samples and data of intensive care were collected. Mechanically ventilated patients with baseline suPAR and PAI-1 measurements were included in the analysis, and healthy volunteers were analysed for comparison. Receiver operating characteristics (ROC), logistic regression, likelihood ratios and Kaplan–Meier analysis were performed.

Results

Baseline suPAR was 11.6 ng/ml (quartiles Q1–Q3, 9.6–14.0), compared to healthy volunteers with suPAR of 0.6 ng/ml (0.5–11.0). PAI-1 concentrations were 2.67 ng/ml (1.53–4.69) and 0.3 ng/ml (0.3–0.4), respectively. ROC analysis for suPAR 90-day mortality areas under receiver operating characteristic curves (AUC) 0.61 (95 % confidence interval (CI): 0.55–0.67), sepsis 0.68 (0.61–0.76), ALI/ARDS 0.64 (0.56–0.73) and RRT 0.65 (0.56–0.73). Patients with the highest quartile of suPAR concentrations had an odds ratio of 2.52 (1.37–4.64, p = 0.003) for 90-day mortality and 3.16 (1.19–8.41, p = 0.02) for ALI/ARDS. In non-operative patients, the AUC’s for suPAR were 90-day mortality 0.61 (0.54–0.68), RRT 0.73 (0.64–0.83), sepsis 0.70 (0.60–0.80), ALI/ARDS 0.61 (0.51–0.71). Predictive value of PAI-1 was negligible.

Conclusions

In non-operative patients, low concentrations of suPAR were predictive for survival and high concentrations for RRT and mortality. SuPAR may be used for screening for patients with potentially good survival. The association with RRT may supply an early warning sign for acute renal failure.     

Midbrain serotonin and striatum dopamine transporter binding in double depression: a one-year follow-up study

Data on neurobiological differences between major depression (MD) and double depression (DD) are scarce. We examined the striatum dopamine (DAT) and midbrain serotonin transporter (SERT) binding of [¹²³I] nor-β-CIT in DD patients (n = 8) and compared it to that in MD patients (n = 11) and healthy controls (n = 19). Drug-naïve patients and controls were imaged by single-photon emission computed tomography at baseline, and the patients also after one year of psychodynamic psychotherapy. Both DD and MD groups had lower midbrain [¹²³I] nor-β-CIT binding compared with the controls. Baseline 17-item Hamilton Depression Rating Scale (HAM-D-17) scores significantly decreased in both groups after one year of psychotherapy (DD: t = 3.55, p = 0.009; MD: t = 5.86, p < 0.001). No differences between the DD and MD groups were observed in age-adjusted baseline striatum or midbrain [¹²³I] nor-β-CIT binding or its change during psychotherapy. Age-adjusted baseline striatum [¹²³I] nor-β-CIT binding correlated inversely with the duration of both dysthymia (rho = −0.76, p = 0.03) and MD (rho = −0.83, p = 0.01) in the DD group. No such finding was observed in the MD group (rho = 0.26, p = 0.44). Baseline HAM-D-17 did not correlate with the change in striatum or midbrain [¹²³I] nor-β-CIT binding in either group. In conclusion, our findings suggest that when using midbrain [¹²³I] nor-β-CIT binding as a marker of SERT binding, no differences are detectable between patients with DD and MD. However, low striatum [¹²³I] nor-β-CIT binding, a marker of DAT binding, may be associated with a longer illness duration in dysthymia.     

Intense cytoplasmic ezrin immunoreactivity predicts poor survival in colorectal cancer

Ezrin is a membrane-cytoskeleton anchor, which, in experimental models, regulates tumor cell invasion and metastatic ability. We carried out immunohistochemical analysis of ezrin in 74 advanced colorectal cancer patients and correlated it to clinicopathologic variables and disease outcome. In contrast to the predominantly membraneous immunoreactivity of normal colorectal epithelium, ezrin expression in the colorectal cells was typically cytoplasmic. Altogether, 16.2% (12/74) of the tumors showed negative/weak ezrin staining, 35.1% (26/74) had moderate staining, and 48.6% (36/74) had intense staining. The expression was more intense in colon than in rectal carcinomas (P = .003). Increased ezrin expression was associated with adverse outcome, that is, shorter disease-specific survival; 48.3 months and 36.6 months for negative-weak versus intense expression (P = .041) as well as shorter survival with metastases at 36 months (P = .030); the metastases₃₆ rates in ezrin_neg/weak, ezrin_moderate, ezrin_intense are 58.3%, 25.0%, and 18.4%, respectively. In univariate survival analysis, dichotomized (negative/weak versus moderate/strong) ezrin expression significantly predicted both the 5-year disease specific survival (P = .035) and 5-year metastases (P = .018) but lost this predictive power in multivariate (Cox) analysis. High ezrin expression was also related to high E-cadherin (cytoplasmic) expression, DNA aneuploidy, and high thymidylate synthase expression (P = .046, P = .042, P = .046, respectively). These results suggest that ezrin may play a role in colorectal cancer progression and that ezrin expression might provide clinically valuable information in predicting the biological behavior of colorectal cancer.