Contribution of hypoxia-measuring molecular imaging techniques to radiotherapy planning and treatment

Hypoxia is related to poor prognosis because it is associated to chemo-and radioresistance. During recent years the evolution of imaging methods like PET/CT and MRI has meant the appearance of new perspectives with direct implications in radiation therapy. We discuss previous experiences in staging, planning and in the follow-up process with these techniques for measuring tumour hypoxia.     

Month‐of‐birth effect on height and weight in Polish rural children

This study investigated a hypothesis of dependence of child height and weight on the month of their birth. The sample comprised 1,241 subjects, 568 boys and 673 girls, age 6–20 years, from villages in Olsztyn Province, Northeast Poland. Individuals' height and weight data were standardized by sex and age to allow grouping of individuals born in the same month irrespective of their sex and age at examination. Subjects born in October to March proved to be significantly taller and heavier than those born in April to September. The magnitude of differences between the semiannual groupings equaled 13.1% of a standard deviation (SD) in height (P = 0.03) and 14.2% of SD in weight (P = 0.02). The month‐of‐birth effect was much stronger for children characterized by high socioeconomic status, where these differences amounted to 39.1% of SD in height (P = 0.02) and 49.4% of SD in weight (P = 0.01). There were no regular changes of the effect with age and no differences between the sexes were found. Fitted cosine functions identified the highest values of examined traits for individuals born in December with the lowest values being found in those born in June. Possible explanations of the month‐of‐birth effect are considered in terms of age categorizing, seasonal variety of growth rates, as well as birth‐related or conception‐related global, hemispheric, and local factors. This study rejects the first two possibilities and suggests this effect requires further research to be conducted in various geographical locations, climates, and cultures, on humans as well as on other species. Am. J. Hum. Biol. 16:31–42, 2004. © 2003 Wiley‐Liss, Inc.     

Efficacy and safety of topical application of human fibrinogen/thrombin-coated collagen patch (TachoComb) for treatment of air leakage after standard lobectomy.

OBJECTIVES: Persisting air leakage after pulmonary resection remains a significant problem. The aim of the study was to evaluate the incidence of air leakage after standard lobectomy and test the efficacy and safety of TachoComb (TC). METHODS: A total of 189 patients undergoing lobectomy were enrolled in a multi-centre, open, randomised, and prospective study to test the efficacy and safety of TachoComb (TC) for air leakage treatment. Air leakage was assessed by water submersion test, and scored as grades 0 if no, 1 if countable, 2 if a stream of and 3 if coalescent bubbles have been observed. Any sites with grade 3 air leakage received further stapling or limited suturing until grade 0, 1 or 2 was obtained. Treatment of air leakage was done with TC or suturing according to randomisation. Air leakage was assessed by further submersion tests. Postoperative air leakage was assessed using the Pleur-Evac system. RESULTS: Overall incidence of air leakage 48+/-6 h after surgery was 34% for TC and 37% for standard treatment (P=0.76). The reduction of intra-operative air leak intensity in the subgroup with grades 1-2 was significantly higher for the TC group (P=0.015). Postoperative air leakage intensity in the subgroup with air leakage grades 1-2 was lower for TC than standard treatment (P=0.047). The mean duration of postoperative air leakage in the subgroup with grades 1-2 was shorter for the TC group than for standard treatment, i.e. 1.9+/-1.4 vs. 2.7+/-2.2 days (P=0.015). CONCLUSIONS: TC could be proven as well-tolerated and safe. In the subgroup of patients with established air leakage, TC showed superior potential in reduction of intra-operative air leakage as well as in reduction of intensity and duration of postoperative air leakage.     

Long-term survival in children under 3 years of age with low-grade astrocytoma

Objective The purpose of this study is to analyze clinical aspects and disease-free survival (DFS) in children less than 3 years of age diagnosed with low-grade astrocytoma. Methods In a period of 24 years (1980–2004), a total of 43 (5.4%) children were registered with these characteristics. Twenty-three patients had pilocytic astrocytoma, 18 diffused, and 2 mixed. Thirty-one (72.1%) children had incomplete surgical tumor resection and 12 (27.9%) had a complete tumor resection. Twelve (27.9%) patients had cranial radiotherapy and 17 (39.5%) received chemotherapy. Overall survival was recorded in 23 (53%). DFS was 50% at 250 months of follow-up for the whole group. DFS for the supratentorial group was 60% at 250 months, whereas, for the infratentorial, it was 22% at 120 months (p = 0.008). Conclusion The only favorable prognostic pattern was the supratentorial presentation. Radiotherapy and chemotherapy did not alter the outcome.     

Treatment of severe acute lung allograft rejection with OKT3 and temporary extracorporeal membrane oxygenation bridging.

OBJECTIVES: The use of OKT3 for treatment of advanced high-grade acute rejection episodes eventually can result in cytokine release and consecutive pulmonary edema. Temporary extracorporeal membrane oxygenation (ECMO) bridging can be used to overcome this crucial period before the beneficial effects of OKT3 can be observed. METHODS: We summarize our experience with three patients, who underwent lung transplantation and presented with severe acute rejection episodes. OKT3 had to be initiated due to insufficient response to standard rejection therapy with corticosteroids. Upon initiation of OKT3 treatment, a massive life-threatening deterioration of lung function in spite of heavily invasive respirator treatment was seen and temporary ECMO support was imperative to support graft function. Results of this treatment were retrospectively reviewed. RESULTS: In all cases femoro-femoral veno-arterial ECMO was used for support of the impaired graft and after a period of 4-5 days led to a massive improvement of graft function. In the further course two patients could be discharged from hospital and are still alive 30 and 36 months, respectively, after the described incident. One patient died 4 months later due to liver failure. CONCLUSIONS: We conclude that the use of ECMO support in patients experiencing significant side effects from OKT3 therapy is a useful and effective therapeutic tool to overcome the initial critical period until the lung has sufficiently recovered.     

Pharmacology of the AC AT Inhibitor Avasimibe (CI‐1011)

Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also by inhibiting the uptake of modified LDL. The concentration‐dependent reduction in cellular cholesteryl ester content in these cells was not accompanied by an increase in intracellular free cholesterol, which is in agreement with a good safety profile for avasimibe. In the liver, avasimibe caused a significant reduction in the secretion of apo B and apo B‐containing lipoproteins into plasma. Avasimibe induced cholesterol 7α‐hydroxylase and increased bile acid synthesis in cultured rat hepatocytes, and its administration to rats did not produce an increase in lithogenicity index of the bile. The hypolipidemic efficacy of the compound was demonstrated in cholesterol‐fed as well as in non‐cholesterol‐fed animals. In these models, plasma cholesterol levels were reduced, mainly due to the decrease in the non‐HDL cholesterol fraction. Clinical data are scarce, but in a study performed in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50–500 mg/day, significantly reduced plasma total triglyceride and VLDL‐cholesterol. Although total cholesterol, LDL‐cholesterol, and HDL‐cholesterol were unchanged, it must be stressed that animal data suggest that avasimibe may have direct antiatherosclerotic activity in addition to its cholesterol‐lowering effect. Avasimibe treatment can also contribute to increase plaque stability, as it reduces the accumulation of lipids in the arterial wall, inhibits macrophage infiltration into the media and reduces matrix metalloproteinase expression and activity. Moreover, avasimibe and statins have been shown to have synergistic effects, and the combination therapy may not only inhibit atherosclerotic lesion progression but also induce lesion regression, independently of changes in plasma cholesterol.