MR-guided laser-induced thermotherapy (LITT) of liver tumours: experimental and clinical data

MR-guided laser-induced interstitial thermotherapy (LITT) is a percutaneous, minimally invasive treatment modality for treating liver lesions/metastases, soft tissue tumours and musculoskeletal lesions. In this group, MR-guided LITT is currently performed under local anaesthesia on an out-patient basis with a specially designed saline-cooled laser application system. Nd:YAG laser (1064?nm wave length) was used for tumour ablation. Magnetic resonance imaging (MRI) using both open and closed MR units has proven clinically effective in validating the exact positioning of optical fibres. It also allows for real time-monitoring of thermal effects and the evaluation of treatment-induced coagulation necrosis. In liver tumours, percutaneous MR-guided LITT achieves a local tumour control rate of 98.7% at 3 months post-therapy and 97.3% at 6 months with metastases smaller than 5?cm in diameter. The mean survival rate for 1259 patients with 3440 metastases treated with 14 694 laser applications at the institute (calculated with the Kaplan-Meier method) was 4.4 years (95% confidence interval: 4.1–4.8?years) and median survival was 3.00 years. No statistically significant difference in survival rates was observed in patients with liver metastases from colorectal cancer vs metastases from other primary tumours. The rate of clinically relevant side effects and complications requiring secondary treatment was 2.2%. The clinical use of MR guided LITT (size<5?cm, number<5) is justified in patients with liver metastases of colorectal and/or breast cancers if the inclusion criteria are carefully observed. Further indications for MR guided LITT include recurrent cancer lesions in the head and neck, lung metastases and bone and soft tissue lesions.     

A phase III trial of recombinant human erythropoietin therapy in nonanemic orthopedic patients subjected to aggressive removal of blood for autologous use: dose, response, toxicity, and efficacy

BACKGROUND: Previous clinical trials have shown that the use of recombinant human erythropoietin (EPO) can facilitate autologous blood donation and reduce allogeneic blood transfusions in autologous blood donors who are anemic at first donation. However, the role of EPO therapy in nonanemic patients remains undefined. To identify this role, a randomized, controlled, multicenter dose-escalation trial was conducted in patients whose initial hematocrit was > 39 percent (0.39). STUDY DESIGN AND METHODS: EPO (150, 300, or 600 units/kg) or placebo was administered intravenously at each of six phlebotomy visits over a 3-week study period. Sixteen (14%) of 116 patients were unable to complete the treatment protocol because of adverse events (n = 11) or for personal reasons (n = 5); 2 patients (1 EPO and 1 placebo) experienced serious adverse events. RESULTS: In 91 evaluable patients, additional red cell production during the study period was 440 +/− 176, 621 +/− 215, 644 +/− 196, and 856 +/− 206 mL (mean +/− SD), respectively, for patients receiving placebo and EPO at 150, 300, and 600 units/kg (p < 0.05 for all EPO groups compared to placebo). However, the percentages of patients in each group who received allogeneic blood did not differ: 2 (9%) of 23 placebo patients and 6 (9%) of 68 EPO patients. CONCLUSION: It is concluded that, while EPO therapy increased preoperative red cell production, no clinical benefit could be demonstrated in autologous blood donors who were not anemic at first blood donation.     

Interleukin-3 and interleukin-7 are alternative growth factors for the same B-cell precursors in the mouse

Clones and lines of precursor (pre) B cells can be established by limiting dilutions of unseparated cell suspensions of fetal liver or bone marrow on stromal cells in the presence of interleukin (IL)-7. When IL-3 is used instead of IL-7, cultures are regularly overgrown by different precursor cells of the myeloid lineage, as well as by adherent cells that inhibit pre-B-cell expansion. However, in the presence of either IL-7 or IL-3, clones of pre-B cells can be established on stroma cells at frequencies near one in one when the cultures are initiated with cell sorter purified CD45RO (B220)+/c-kit+ fetal liver or bone marrow derived pre-B cells. Clones grown on stromal cells in the presence of IL-7 can be regrown in IL-3, and vice versa. Pre-B cells that proliferate on stromal cells in the presence of IL-7 or IL-3 have the same phenotype, ie, are B220+ c-kit+, CD43+, and surrogate light chain+. Removal of the growth factors (IL-7, respectively IL-3) from the cultures results in differentiation to surface immunoglobulin (slg) positive, c-kit-, CD43-, surrogate light chain- B cells, a fraction of which is lipopolysaccharide (LPS) responsive as shown by IgM secretion. These results show that IL-7 and IL-3 stimulate largely overlapping populations of precursor B cells from bone marrow to proliferate for long periods of time in the presence of stromal cells. Thus, IL-7 and IL-3 are alternative growth factors for the same pre-BI cell.     

Dermatitis as a side-effect of long-term topical treatment with certain beta-blocking agents

Three groups of glaucoma patients, treated topically with various beta-blocking agents, were studied for mucocutaneous side-effects of long-term therapy. In five of eleven patients with ocular and/or periocular dermatitis as an adverse reaction to long-term treatment with metoprolol eye drops a dermatitis, reproducible by patch tests with pure metoprolol 3%, was demonstrable. Histopathological examination of positive patch tests examined in three cases showed a picture compatible with a delayed type of hypersensitivity. Four atenolol treated patients showed adverse reactions, but negative patch tests to atenolol were found. In addition new data are reported in favour of cross-reactivity between certain beta-blocking agents.     

Atypical fibroxanthoma of the skin

A typical fibroxanthoma is a solitary tumour of the skin, which occurs mostly on sun-exposed areas in elderly people. The diagnosis can only be made with certainty on the typical histological findings, which suggest a bizarre malignant tumour. Although metastasizing tumours are reported in the literature, the authors believe that the true atypical fibroxanthoma is benign. Correct diagnosis obviates the need for unnecessary radical surgery. The possibility of atypical fibroxanthoma should always be considered when a histologically bizarre tumour is found on sun-damaged or irradiation-damaged skin in elderly patients or on previously traumatized sites. In this paper five cases are added to the 346 cases culled from the literature. Electron microscopic investigations in one case demonstrated cells with delicate cytoplasmic fibrils in small bundles. This does not necessarily suggest filaments of myofibroblasts, as has been previously reported.     

Strong relationship between NT‐proXNP levels and cardiac output following cardiac surgery in neonates and infants

Background: NT‐proXNP, a new natriuretic peptide analyte, incorporates information about the concentrations of both N‐terminal pro‐atrial and pro‐brain natriuretic peptides (NT‐proANP, NT‐proBNP). We aimed to investigate whether NT‐proXNP is a reliable indicator of the cardiac index (CI) and the hemodynamic state in neonates and infants undergoing an open heart surgery. Methods: We enrolled 26 children under the age of 1 year into this prospective study. All patients underwent an elective cardiac operation with cardiopulmonary bypass (CPB) to achieve complete biventricular repair. Peri‐operative hemodynamic parameters were assessed by transpulmonary thermodilution and natriuretic peptide levels were recorded. Results: The NT‐proXNP level correlated significantly with the simultaneously measured NT‐proANP level (r=0.60, P<0.001), but more strongly with the NT‐proBNP level (r=0.89, P<0.001) and the arithmetic sum of both (r=0.88, P<0.001). NT‐proXNP had a strong correlation with CI (r=?0.85, P<0.001), the stroke volume index (r=?0.80, P<0.001) and the global ejection fraction (r=?0.67, P<0.009) throughout the post‐operative period. Conventionally measured parameters such as heart rate, mean arterial pressure and pulse‐pressure product exhibited weaker correlations with CI than NT‐proXNP. Among laboratory values, creatinine levels correlated significantly with CI (r=?0.77, P<0.001) and NT‐proXNP (r=0.76, P<0.001) during the post‐operative period. A post‐operative NT‐proXNP level of 3079 pmol/l was diagnostic for CI <3 l/min/m² with 89% sensitivity and 90% specificity (area under the curve: 0.91 ± 0.05). Conclusion: NT‐proXNP is a good marker of cardiac output following pediatric cardiac surgery and might be a useful tool in the recognition of a low output state.     

The financial protection effect of Ghana National Health Insurance Scheme: evidence from a study in two rural districts

Background  

One of the key functions of health insurance is to provide financial protection against high costs of health care, yet evidence of such protection from developing countries has been inconsistent. The current study uses the case of Ghana to contribute to the evidence pool about insurance's financial protection effects. It evaluates the impact of the country's National Health Insurance Scheme on households' out-of-pocket spending and catastrophic health expenditure.     

Preclinical characterization of WAY-211612: a dual 5-HT uptake inhibitor and 5-HT1A receptor antagonist and potential novel antidepressant

Background and purpose

As a combination of 5-HT selective reuptake inhibitor (SSRI) with 5-HT_1A receptor antagonism may yield a rapidly acting antidepressant, WAY-211612, a compound with both SSRI and 5-HT_1A receptor antagonist activities, was evaluated in preclinical models.

Experimental approach

Occupancy studies confirmed the mechanism of action of WAY-211612, while its in vivo profile was characterized in microdialysis and behavioural models.

Key results

WAY-211612 inhibited 5-HT reuptake (K_i = 1.5 nmol·L⁻¹; K_B = 17.7 nmol·L⁻¹) and exhibited full 5-HT_1A receptor antagonist activity (K_i = 1.2 nmol·L⁻¹; K_B = 6.3 nmol·L⁻¹; I_max 100% in adenyl cyclase assays; K_B = 19.8 nmol·L⁻¹; I_max 100% in GTPγS). WAY-211612 (3 and 30 mg·kg⁻¹, po) occupied 5-HT reuptake sites in rat prefrontal cortex (56.6% and 73.6% respectively) and hippocampus (52.2% and 78.5%), and 5-HT_1A receptors in the prefrontal cortex (6.7% and 44.7%), hippocampus (8.3% and 48.6%) and dorsal raphe (15% and 83%). Acute or chronic treatment with WAY-211612 (3–30 mg·kg⁻¹, po) raised levels of cortical 5-HT approximately twofold, as also observed with a combination of an SSRI (fluoxetine; 30 mg·kg⁻¹, s.c.) and a 5-HT_1A antagonist (WAY-100635; 0.3 mg·kg⁻¹, s.c). WAY-211612 (3.3–30 mg·kg⁻¹, s.c.) decreased aggressive behaviour in the resident-intruder model, while increasing the number of punished crossings (3–30 mg·kg⁻¹, i.p. and 10–56 mg·kg⁻¹, po) in the mouse four-plate model and decreased adjunctive drinking behaviour (56 mg·kg⁻¹, i.p.) in the rat scheduled-induced polydipsia model.

Conclusions and implications

These findings suggest that WAY-211612 may represent a novel antidepressant.