Statistical analysis of target motion in gated lung stereotactic body radiation therapy

An external surrogate-based respiratory gating technique is a useful method to reduce target margins for the treatment of a moving lung tumor. The success of this technique relies on a good correlation between the motion of the external markers and the internal tumor as well as the repeatability of the respiratory motion. In gated lung stereotactic body radiation therapy (SBRT), the treatment time for each fraction could exceed 30 min due to large fractional dose. Tumor motion may experience pattern changes such as baseline shift during such extended treatment time. The purpose of this study is to analyze tumor motion traces in actual treatment situations and to evaluate the effect of the target baseline shift in gated lung SBRT treatment. Real-time motion data for both the external markers and tumors from 51 lung SBRT treatments with Cyberknife Synchrony technology were analyzed in this study. The treatment time is typically greater than 30 min. The baseline shift was calculated with a rolling average window equivalent to ～20 s and subtracted from that at the beginning. The magnitude of the baseline shift and its relationship with treatment time were investigated. Phase gating simulation was retrospectively performed on 12 carefully selected treatments with respiratory amplitude larger than 5 mm and regular phases. A customized gating window was defined for each individual treatment. It was found that the baseline shifts are specific to each patient and each fraction. Statistical analysis revealed that more than 69% treatments exhibited increased baseline shifts with the lapse of treatment time. The magnitude of the baseline shift could reach 5.3 mm during a 30 min treatment. Gating simulation showed that tumor excursion was caused mainly by the uncertainties in phase gating simulation and baseline shift, the latter being the primary factor. With a 5 mm gating window, 2 out of 12 treatments in the study group showed significant tumor excursion. Baseline shifts alone could cause up to 20% of tumor excursion outside the gating window. It is concluded that baseline shifts may increase with the treatment time and are more likely to act as a time-dependent systematic error. For phase-based gated lung SBRT, a baseline shift may be one of the major sources of targeting error during treatment.     

Physical activity patterns and estimated daily energy expenditures in normal and overweight tunisian schoolchildren

Our aim was to test the normality of physical activity patterns and energy expenditures in normal weight and overweight primary school students. Heart rate estimates of total daily energy expenditure (TEE), active energy expenditure (AEE), and activity patterns were made over 3 consecutive school days in healthy middle-class Tunisian children (46 boys, 44 girls, median age (25^th-75^th) percentile, 9.2 (8.8-9.9) years. Our cross-section included 52 students with a normal body mass index (BMI) and 38 who exceeded age-specific BMI limits. TEE, AEE and overall physical activity level (PAL) were not different between overweight children and those with a normal BMI [median values (25^th-75^th) 9.20 (8.20-9.84) vs. 8.88 (7.42-9.76) MJ/d; 3.56 (2.59-4.22) vs. 3.85 (2.77-4.78) MJ/d and 1.74 (1.54-2.04) vs. 1.89 (1.66-2.15) respectively]. Physical activity intensities (PAI) were expressed as percentages of the individual’s heart rate reserve (%HRR). The median PAI for the entire day (PAI₂₄) and for the waking part of day (PAI_w) were lower in overweight than in normal weight individuals [16.3 (14.2-18.9) vs. 20.6 (17.9-22.3) %HRR, p < 0.001) and 24.8 (21.6-28.9) vs.26.2 (24.5-30.8) %HRR, p < 0.01], respectively. Overweight children allocated more of their day to sedentary pursuits [385 (336-468) vs 297 (235-468) min/d, p < 0.001], and less time to moderate physical activity [381(321-457) vs. 460 (380-534) min/d, p < 0.01]. Nevertheless, because of the greater energy cost of a given task, total and active daily energy expenditure did not differ from those with a normal BMI.

Key points

• The physical activity intensity for the entire day (PAI₂₄) and for the waking part of day (PAI_w) were lower in overweight than in normal weight individuals.
• However, because the energy cost of activity is greater in those who are overweight, they do not differ in total energy expenditure or in active energy expenditure.
• Normal children spend more time in moderate activity and less time in sedentary pursuits than overweight children.

Key words: Heart rate monitoring, activity patterns, energy expenditure, excess weight, obesity.     

Long-term results (up to 18 years) of balloon angioplasty on systemic hypertension in adolescent and adult patients with coarctation of the aorta

BACKGROUND: Little is known regarding the long-term follow-up results of balloon angioplasty (BA) for patients with aortic coarctation (AC) on systemic hypertension. HYPOTHESIS: To define the long-term effect of BA of AC on systemic hypertension in adolescent and adult patients. METHODS: Follow-up data of 53 patients (36 male), mean age 24 +/- 9 years, undergoing BA for discrete AC at median interval of 11.8 years (range, 4-18 years), including cardiac catheterization, magnetic resonance imaging (MRI), and echocardiography. Patients were divided into two groups at 1 year after BA on the basis of absence (group A: 40 patients) or presence (group B: 11 patients) of persistent hypertension and need for medication. RESULTS: Fifty-one patients had baseline hypertension, BA produced an immediate reduction in peak AC gradient from 66 +/- 23 mmHg to 10.8 +/- 7 mmHg (p < 0.0001). The immediate systolic blood pressure (SBP) decreased from 165 +/- 17 mmHg (95% CI: 159 to 171) to 125 +/- 10 mmHg (95% CI: 122 to 131) (p < 0.001) in 40 patients (group A) and from 184 +/- 19 mmHg (95% CI: 169 to 198) to 142 +/- 22 mmHg (95% CI: 124 to 156) (p<0.001) in 11 patients (group B). At 1-year follow-up, SBP decreased further to 115 +/- 10 in group A (95% CI 111-119) and 134 +/- 19 in group B (95% CI 122-142) (p<0.001). The blood pressure had normalized without medication in group A (165 +/- 17 to 115 +/- 10 mmHg). CONCLUSION: Long-term results of BA for discrete AC are excellent and should be considered as the first option for treatment of this disease. No paradoxical hypertension occurred post angioplasty, and normalization of blood pressure without medication occurred in 78% of the patients after BA.     

Diaphragme sous-aortique par muscularisation de grande valve mitrale : à propos de deux cas

Subaortic stenosis was considered for a long time as a congenital anomaly, but it is considered now as an acquired form of obstacle to the left ventricle ejection. It constitutes 8 to 20% of the causes of obstacle left ventricle. Ventricular septal defect and aortic coarctation are the most frequent anomalies associated with the subaortic stenosis. The anomalies of mitral valve and especially muscularization of the anterior mitral valve leaflet remain very rare and underestimated. The diagnosis is made by the echocardiography and must be systematically looked for because its misunderstanding in preoperative can be at the origin of recurrences. We report in this work two cases of muscularization of the anterior mitral valve leaflet associated to subaortic stenosis. Through these cases and through a review of the literature, we are going to put the point on this rare anomaly.     

Sacrococcygeal pilonidal disease: sinotomy versus excisional surgery, a retrospective study

Pilonidal disease is a disease of relatively young people, the exact aetiology of which is unknown. Treatment options vary from simple incision to complex flap procedures. Each method has its advocates and they all have a variable recurrence rate. The multiplicity of procedures testifies to the lack of an optimal treatment method. The objective of this study is to compare sinotomy, that is, simply laying the sinus open with the more popular radical surgery, where the sinus-bearing tissues are excised. Patients who were admitted to Aseer Central Hospital, Saudi Arabia with a pilonidal sinus or abscess, in the period from April 1999 to January 2005, were identified. The medical records were reviewed and data related to the patient characteristics, disease process and the procedures carried out were noted. Identified patients were contacted by phone to check recurrence of the disease and their abidance to instructions regarding regular hair removal from the area. Eighty-one patients were included in the study. The median age was 24.2 years (range 16-60 years). There were 9 women and 72 men. All procedures were carried out under general anaesthesia except sinotomy, which was carried out under general or local anaesthesia. The surgical procedure was incision and drainage of abscess in 16 cases (19.8%), excision with primary closure in 29 cases (35.8%), excision by the open method in 15 cases (18.5%), sinotomy in 14 cases (17.3%) and rhomboid flap construction in 8 cases (9.9%). The overall recurrence rate was 26.9%, and the mean hospital stay was 4.1 days. Sinotomy had a low recurrence rate (12.5%) and a short hospital stay (2.8 days). Sinotomy has the advantages of simplicity, the possibility of operating under local anaesthesia, with an acceptable recurrence rate. We recommend sinotomy for pilonidal sinus and abscess alike, both in primary and recurrent cases.     

Expression of the CD36 homolog (FAT) in fibroblast cells: effects on fatty acid transport.

An adipocyte membrane glycoprotein, (FAT), homologous to human CD36, has been previously implicated in the binding/transport of long-chain fatty acids. It bound reactive derivatives of long-chain fatty acids and binding was specific and associated with significant inhibition of fatty acid uptake. Tissue distribution of the protein and regulation of its expression were also consistent with its postulated role. In this report, we have examined the effects of FAT expression on rates and properties of fatty acid uptake by Ob17PY fibroblasts lacking the protein. Three clones (P21, P22, and P25) were selected based on FAT mRNA and protein levels. Cell surface labeling could be demonstrated with the anti-CD36 antibody FITC-OKM5. In line with this, the major fraction of immunoreactive FAT was associated with the plasma membrane fraction. Assays of oleate and/or palmitate uptake demonstrated higher rates in the three FAT-expressing clones, compared to cells transfected with the empty vector. Clone P21, which had the highest protein levels on Western blots, exhibited the largest increase in transport rates. Fatty acid uptake in FAT-expressing P21 cells reflected two components, a phloretin-sensitive high-affinity saturable component with a Km of 0.004 microM and a basal phloretin-insensitive component that was a linear function of unbound fatty acid. P21 cells incorporated more exogenous fatty acid into phospholipids, indicating that binding of fatty acids was followed by their transfer into the cell and that both processes were increased by FAT expression. The data support the interpretation that FAT/CD36 functions as a high-affinity membrane receptor/transporter for long-chain fatty acids.     

Characterization of pig liver purified cytochrome P-450 isoenzymes for ochratoxin A metabolism studies.

In this paper, we report the characterization of 4 isolated, constitutive cytochrome P-450 fractions from pig liver microsomes. The two predominant forms, A2 and A3, exhibit several similarities: a Mr of 54 kDa, a lambda max CO-Fe++ at 448 nm, a relatively high ratio of the high-spin form and an immunological cross-reaction with polyclonal antibodies against rat liver P-450 IIB1. It is shown that these forms and the minor form Ba, which are active as benzphetamine N-demethylase, play an important metabolic role in ochratoxin A oxidation. This mycotoxin was oxidized by at least 3 different pig liver cytochrome P-450 fractions, each producing different metabolites, namely (4R)-, (4S)-hydroxyochratoxin A, and a new lipophilic metabolite. Since the pig is particularly susceptible to ochratoxin A toxicity, it represents a good animal model for in vitro studies of the metabolism of such a xenobiotic.     

Is bile acid a determinant of the gut microbiota on a high-fat diet?

Recently, we discovered that bile acid, a main component of bile, is a host factor that regulates the composition of the cecal microbiota in rats. Because bile secretion increases on a high-fat diet and bile acids generally have strong antimicrobial activity, we speculated that bile acids would be a determinant of the gut microbiota in response to a high-fat diet. The observed changes in the rat cecal microbiota triggered by cholic acid (the most abundant bile acid in human biliary bile) administration resemble those found in animals fed high-fat diets. Here, we discuss the rationale for this hypothesis by evaluating reported diet-induced gut microbiota alterations based on the postulate that bile acids worked as an underlying determinant. The identification of host factors determining the gut microbiota greatly contributes to understanding the causal relationships between changes in the gut microbiota and disease development, which remain to be elucidated.