The effect of fraction time in intensity modulated radiotherapy: theoretical and experimental evaluation of an optimisation problem.

BACKGROUND AND PURPOSE: In intensity modulated radiotherapy (IMRT), the complexity and the number of treatment fields have expanded. This may imply that the delivery time for each fraction becomes prolonged. In a number of IMRT techniques used in the clinic, the delivery time per fraction is usually 10-15 min, sometimes more than 15 min. In studies on human skin, prolonged delivery time is shown to cause significant reduction of radiation effects compared with acute irradiation. In this paper the effect of changes in fraction delivery time was studied by in vitro irradiation of mammalian cells. MATERIAL AND METHODS: Chinese hamster fibroblasts (V79-379-A) were used for simulating clinical situations. Most experiments were performed with 2Gy/fraction with 4-h intervals in 40-60 replicates. Each fraction was divided into different subfractions, simulating the delivery of a complicated treatment. The effect of changing the delivery time for each fraction was studied. Parameters for the cell survival curve and repair kinetics were determined experimentally. The same methods were also used for large fraction sizes (8Gy). The validity of the most widely used models in the literature, all derived from linear-quadratic formalism, were tested against the experimental results. RESULTS: The effect of prolonging the fraction time for 2-Gy fractions was underestimated by the biological models. The experiments showed that 10-min prolonged delivery time gave a ratio between surviving fractions at 2Gy (S-ratio) of 1.054 with a 95% confidence interval (CI) 1.030-1.080, while the models predicted 1.007 and 1.009. Extending the fraction time to 20 min gave an S-ratio of 1.063 with CI of 1.045-1.080, while the models predicted 1.012 and 1.014. For 8-Gy fractions, there was a good agreement between predications and experimental results. The ratio between surviving fractions at 8Gy is 1.370 with CI of 1.300-1.440, while the models predicated 1.37 and 1.35. CONCLUSIONS: The effect of prolonging fraction time at conventional dose/fraction is underestimated by biological models. Prolonging the fraction time will spare tissues with a fast DNA repair. There is a risk for sparing tumours. This should be considered when IMRT technique is implemented in the clinic.     

Unilateral neglect: further validation of the baking tray task.

OBJECTIVE: The Baking Tray Task is a comprehensible, simple-to-perform test for use in assessing unilateral neglect. The aim of this study was to validate further its use with stroke patients. METHODS: The Baking Tray Task was compared with 2 versions of the Behaviour Inattention Test and a test for personal neglect. A total of 270 patients were subjected to a 3-item version of the Behaviour Inattention Test and 40 patients were subjected to an 8-item version of the Behaviour Inattention Test, besides the Baking Tray Task and the personal neglect test. RESULTS: The Baking Tray Task was more sensitive than the 3-item Behaviour Inattention Test, but the 8-item Behaviour Inattention Test was more sensitive than the Baking Tray Task. The best combination of any 3 tests was Baking Tray Task, Reading an article, and Figure copying; the 2 last-mentioned being a part of the 8-item Behaviour Inattention Test. CONCLUSION: Multi-item tests detect more cases of neglect than do single tests. However, it is tiresome for the patient to undergo a larger test battery than necessary. It is also time-consuming for the staff. Behavioural tests seem more appropriate when assessing neglect. The Baking Tray Task seems to be one of the most sensitive single tests, but its sensitivity can be further enhanced when it is used in combination with other tests.     

Differences in CMV-Specific T-Cell Levels and Long-Term Susceptibility to CMV Infection after Kidney, Heart and Lung Transplantation

Patients after kidney, heart and lung transplantation differ in their immunosuppressive drug regimens and in susceptibility to infectious complications with cytomegalovirus (CMV). In this study, CMV-specific T-cell responses were characterized in long-term transplant recipients and associated with the frequency of infectious complications. CMV-reactive CD4 T cells from 50 healthy controls, 68 renal, 14 heart and 24 lung transplant recipients were flow cytometrically quantified by the induction of cytokines after specific stimulation. Moreover, the immunosuppressive effect of calcineurin inhibitors on specific T-cell reactivity was quantified in vitro and compared with responses in vivo. Median CMV-specific T-cell frequencies in long-term renal (1.48%; range 0.06-17.26%) and heart transplant recipients (0.90%; 0.13-12.49%) did not differ from controls (1.82%; 0.26-21.00%). In contrast, CMV-specific T-cell levels were significantly lower in lung transplant recipients (0.50%; <0.05-4.98%) and showed a significant correlation with the frequency of infectious episodes (r =-0.57, p = 0.005). The differences within the groups were associated with increasing dosages of immunosuppressive drugs, as exemplified for calcineurin inhibitors that dose dependently reduced specific T-cell reactivity in vitro. In conclusion, monitoring CMV-specific CD4 T cells may serve as a measure for long-term disease susceptibility and may contribute to an improved management of CMV complications after lung transplantation.     

Use of antibiotic and analgesic drugs during lactation.

During lactation, multiple situations can arise that require maternal pharmacological treatment. Because of the many health advantages of human milk to infants, breast feeding should be interrupted only when the needed drug might be harmful to the nursing child and exposure via the breast milk will be sufficient to pose a risk. Since the majority of drugs have not been shown to cause adverse effects when used during lactation, and even temporary interruption of breast feeding can be difficult for the nursing dyad, decisions regarding maternal medication use during breast feeding should be based on accurate and up-to-date information. This article reviews available data on the most commonly used antibiotics and analgesics. The use of most antibiotics is considered compatible with breast feeding. Penicillins, aminopenicillins, clavulanic acid, cephalosporins, macrolides and metronidazole at dosages at the low end of the recommended dosage range are considered appropriate for use for lactating women. Fluoroquinolones should not be administered as first-line treatment, but if they are indicated, breast feeding should not be interrupted because the risk of adverse effects is low and the risks are justified. Paracetamol (acetaminophen), low-dose aspirin (acetylsalicylic acid) [up to 100 mg/day] and short-term treatment with NSAIDs, codeine, morphine and propoxyphene are considered compatible with breast feeding. Safer alternatives should be considered instead of dipyrone, aspirin at a dosage >100 mg/day and pethidine (meperidine). In the light of the many safe alternatives for pain control, breast-feeding mothers should not be allowed to experience pain or be made to feel that they must choose between analgesia and breast feeding.     

Interleukin 1 receptor antagonist (IL1RA) in acute leukaemia: IL1RA is both secreted spontaneously by myelogenous leukaemia blasts and is a part of the acute phase reaction in patients with chemotherapy- induced leucopenia

Abstract: Blast cells derived from peripheral blood of patients with acute myelogenous leukaemia (AML) were cultured in vitro and interleukin 1 receptor antagonist (IL1RA) concentrations determined in culture supernatants. AML blasts derived from patients classified as AML-M4 and AML-M5 subtype showed an increased release of IL1RA. IL1α and IL1β caused a similar increase in AML blast release of IL1RA, and addition of anti-ILl antibodies decreased IL1RA release. IL1RA release from AML blasts was also increased by stem cell factor, tumour necrosis factor α (TNFα), granulocyte-macrophage colony-stimulating factor and macrophage colony-stimulating factor, whereas interleukin 3, interleukin 6, leukaemia inhibitory factor and granulocyte colony- stimulating factor did not significantly alter IL1RA release. When investigating IL1RA serum levels, serum concentrations were decreased in acute leukaemia patients with chemotherapy-induced cytopenia compared with healthy controls. Serum levels of both IL1RA as well as IL1β and soluble TNFα receptors increased when the leucopenic patients developed complicating bacterial infections.     

Characterization of exposure to molds and actinomycetes in agricultural dusts by scanning electron microscopy, fluorescence microscopy and the culture method

Air samples from 79 farms with 10(5) to 10(11) microorganisms/m3 were analyzed by scanning electron microscopy (SEM), fluorescence microscopy (FM), and the culture method. The total exposure to microorganisms (particularly actinomycetes) was underestimated when assessed as colony-forming units (cfu). The average cfu count was one-sixth of the total count according to SEM or FM, and the individual variability was great. This occurrence was partly explained by the aggregation of spores. Single spores accounted for 2-65% of all spores in 35 samples. There was an average of three spores/particle, and 93 (range 67-100)% of the spores were single or in aggregates of respirable size. Aggregation was more pronounced for actinomycetes and at high spore counts. Actinomycetes and bacteria could not be distinguished by FM. Bacteria (other than actinomycetes) were not detected by SEM, yet the total count of microorganisms was similar for FM and SEM. Most particles were spores from actinomycetes and fungi of the genera Aspergillus or Penicillium.     

Enhanced Intestinal Absorption of Oxytocin Peptide Analogues in the Absence of Pancreatic Juice in Pigs

Purpose. The present investigation was done to study the intestinal absorption of three oxytocin peptide analogues and to elucidate the role of pancreatic juice on their absorption. Methods. In conscious chronically catheterized pigs (6–8 weeks of age) plasma concentration of the peptides, [Mpa¹, D-Tyr(Ethyl)², Thr⁴, Orn⁸]-oxytocin (F314), [Mpa¹, D-Tyr(Ethyl)², Val⁴, D-Arg⁸]-oxytocin (CAT), and [Mpa¹, D-Tyr(Ethyl)², Thr⁴, Orn⁸, desGly⁹, carba⁶]-oxytocin (F327) after intraduodenal administration, during presence or diversion of the pancreatic juice via a pancreatic duct catheter, were determined by radioimmunoassay. The stability of the peptides to degradation was determined in vitro by incubation with activated pancreatic juice, chymotrypsin or trypsin, followed by reversed phase HPLC analyses. Results. All peptides were absorbed with a bioavailability of about 0.5% in the presence of pancreatic juice, but increased to 1.0%, 2.1%, and 13.5% for F314, CAT, and F327, respectively, when the pancreatic juice was diverted from the intestine. After incubation with pancreatic juice 95% of F314, 98% of F327, and 100% of CAT was found intact. When incubated with trypsin CAT remained intact while F314 and F327 were degraded by 54% and 46%, respectively. Incubation with purified chymotrypsin did not degrade the test peptides. Conclusions. The results indicate that the increased absorption of peptides observed under conditions of diverted pancreatic juice cannot only be explained by the absence of pancreatic enzymes, but also by changed absorptive properties in the gastrointestinal tract.