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Background: In patients with colorectal liver metastases (CLM) R0 resection significantly improves overall survival (OS).Methods: In this report, we present the results of a phase II trial of FOLFOX6+bevacizumab in patients with non-optimally resectable CLM. Patients received six cycles of FOLFOX6+ five of bevacizumab. Patients not achieving resectability received six additional cycles of each. A PET-CT was performed at baseline and again within 1 month after initiating treatment.Results: From September 2005 to July 2009, 21 patients were enrolled (Male/Female: 15/6; median age: 65 years). An objective response (OR) was documented in 12 cases (57.1%; complete responses (CRs): 3, partial response (PR): 9); one patient died from toxicity before surgery. Thirteen patients underwent radical surgery (61.9%). Three (23%) had a pathological CR (pCR). Six patients (46.1%) experienced minor postsurgical complications. After a median 38.8-month follow-up, the median OS was 22.5 months. Patients achieving at least 1 unit reduction in Standard uptake value (SUV)max on PET-CT had longer progression-free survival (PFS) (median PFS: 22 vs 14 months, P=0.001).Conclusions: FOLFOX6+bevacizumab does not increase postsurgical complications, yields high rates of resectability and pCR. Early changes in PET-CT seem to be predictive of longer PFS. [ABSTRACT FROM AUTHOR]

Individuals in a structural physical training program can show beneficial changes in body composition, such as body fat reduction and muscle mass increase. This study measured body composition changes by using 3 different techniques-skinfold thickness (SF) measurements, air displacement plethysmography (BOD-POD), and dual-energy x-ray absorptiometry (DXA)-during 9 months of intense training in healthy young men engaged in military training. Twenty-seven young men were recruited from a special faction of the Italian Navy. The program previewed three phases: ground combat, sea combat, and amphibious combat. Body composition was estimated at the beginning, in the middle, and at the end of the training. After the subjects performed the ground combat phase, body composition variables significantly decreased: body weight (P < 0.05), fat-free mass (FFM) (P < 0.001), and fat mass (FM) (P < 0.03). During the amphibious combat phase, body weight increased significantly (P < 0.01), mainly because of an increase in FFM (P < 0.001) and a smaller mean decrease in FM. There was a significant difference (P < 0.05) in circumferences and SF at various sites after starting the training course. Bland-Altman analysis did not show any systematic difference between FM and FFM measured with the 3 different techniques on any occasion. On any visit, FFM and FM correlation measured by BOD-POD (P = 0.90) and DXA was significantly greater than measured by SF. A significant difference was found in body mass index (BMI) measured during the study. BOD-POD and SF, compared with DXA, provide valid and reliable measurement of changes in body composition in healthy young men engaged in military training. In conclusion, the findings suggest that for young men of normal weight, changes in body weight alone and in BMI are not a good measure to assess the effectiveness of intense physical training programs, because lean mass gain can masquerade fat weight loss. [ABSTRACT FROM AUTHOR]

The mechanisms underlying altered BP regulation in congestive heart failure are unknown. This study examines the possibility that differences in circadian blood pressure (BP) regulation between the normal and the failing heart correlate with changes in the circulating pattern of atrial natriuretic peptide (ANP). Twelve normotensive patients with coronary artery disease were studied over two separate 24-h periods, the first during acute exacerbation of congestive heart failure (radionuclide-determined ejection fraction at rest was less than 30%) and the second after therapy-induced functional recovery (ejection fraction was more than 40%). BP monitoring at 10-min intervals and intra-atrial blood samples for ANP assays at hourly intervals were obtained. Significant correlations between eject ion fraction and the indexes of circadian BP variability (standard deviation of the 24-h pressure mean and day-night pressure difference) were found both before and after treatment. Ejection fraction was independent of the BP means (24-h, daytime and night-time). BP variability, 24-h mean and daytime mean were higher after treatment. A NP means were lower after treatment, whereas A NP variability was higher. The indexes ofBP and ANP variability correlated both before and after treatment, whereas the BP and the ANP means were independent. These findings demonstrate that differences in BP regulation of CHF before and after effective treatment correlate with changes in the circulating pattern of ANP. We speculate that by modulating ANP release, the heart could be actively involved in BP regulation as part of the compensatory mechanisms aimed at protecting against circulatory overload. [ABSTRACT FROM PUBLISHER]

The main lesions of the skull and hand, observed in a group of hypertransfused beta-thalassaemic patients, are compared with a control group of low-transfused patients. Bony abnormalities reflect the relationship between proliferating bone marrow and bone cortex, and hypertransfusion therapy will prevent development of lesions only if established early in life. If this is done, the diploë in the skull may become normal, overgrowth of facial bone is moderate, pneumatisation of the paranasal sinuses is not completely prevented, and the "hair-brush" pattern may disappear completely. A normal appearance of the hand in adequately treated patients differentiates between prepubertal patients and adults. [ABSTRACT FROM AUTHOR]

AIMS--To assess the pharmacokinetics of oral, intramuscular, or transdermal hormone replacement in patients with beta thalassaemia major. METHODS--Oral (testosterone undecanoate 40 mg) and intramuscular (testosterone propionate 15 mg, phenylpropionate 30 mg, isocaproate 30 mg and decanoate 50 mg) testosterone and transdermal (17 beta oestradiol 25 micrograms and 50 micrograms) oestradiol were evaluated in 21 male (16-29 years) and 11 female (19-26 years) patients with beta thalassaemia major and various forms of hypogonadism. RESULTS--In male patients given oral testosterone, peak testosterone concentrations were observed either two to four hours or seven hours after administration; intramuscular testosterone produced peak values seven days after injection. Transdermal 17 beta oestradiol given to female patients produced a biphasic pattern with an initial peak concentration occurring at 36 hours and a secondary rise at 84 hours. CONCLUSIONS--The results indicate that oral androgens should be given twice daily in cases of hypogonadism, and where growth is incomplete, lower than recommended doses. If intramuscular testosterone is used, smaller doses of 10-25 mg should be given every one to two weeks. Transdermal administration of 25-50 micrograms 17 beta oestradiol generally produces a plasma E2 value in the early to mid-follicular phase range (100-300 pmol/l). This is appropriate in adults but excessive for prepubertal girls. Diffuse iron infiltration of tissues does not seem to interfere with the absorption of androgens and oestrogens from the gut, muscle, or skin. [ABSTRACT FROM PUBLISHER]

Endocrine studies were made on 23 female patients aged 13 to 29 years, with delayed puberty or primary amenorrhoea and beta thalassaemia major, and 12 healthy controls, of whom six were prepubertal and six were in Tanner's stage 3-4. Each patient and control received a single intravenous dose of 100 micrograms gonadotrophin releasing hormone (GnRH), and one week later, 10 U/kg body weight of human menopausal gonadotrophin (hMG) to stimulate ovarian function. The patients had decreased gonadotrophin reserves when compared with those of normal controls, only one of 23 patients had an intact luteinising hormone and follicle stimulating hormone response. Most of the thalassaemic patients with delayed puberty showed normal gonad response to human menopausal gonadotrophin (hMG), but three had very low responses, when compared with that of controls. The gonadal failure was even more severe in four of six patients with primary amenorrhoea. It is important to assess hypothalamic-pituitary-gonadal function in young women with beta thalassaemia major, so that those with glandular dysfunction may be started on replacement therapy. [ABSTRACT FROM PUBLISHER]

Insulin and glucagon secretion were studied during an oral glucose tolerance test and arginine infusion in 11 patients with thalassaemia intermedia, who showed laboratory evidence of iron overload. Mean blood glucose concentrations in patients with thalassaemia intermedia were significantly higher than normal and 3 of 11 patients had impaired glucose tolerance. The principal abnormality appears to be a deficiency in insulin and glucagon from the pancreas in response to oral glucose tolerance and arginine stimulation tests. Several factors, such as iron overload, chronic hypoxia, zinc deficiency and increased catecholamine production secondary to anaemia, might play a part in the pathogenesis of these abnormalities. Each of these factors affect individual cases to a varied degree. Our data emphasize the mildness of carbohydrate defect as compared to the degree of insulinopenia and indicate the necessity for prescribing measures which prevent excessive iron deposition and improve iron excretion in thalassaemic patients with iron overload. [ABSTRACT FROM PUBLISHER]

The aim of this study was to compare a recent multiple allergosorbent chemiluminescent assay (MAST-CLA) with the RAST for the diagnosis of inhalant allergic disease in 232 patients with rhinitis and/or bronchial asthma. As judged by concordance of clinical history, skin prick tests to a range of six allergens common to our geographic area, and by nasal provocation tests, 70 patients were non-allergic and 162 allergic: 70 to grasses, 46 to mites, four to mugwort, eight to peilitory, and 34 were sensitive to several allergens. In our patient sample that, among other things, comprises subjects with fairly rare monoallergies, MAST-CLA testing gave results which closely corresponded to positive RAST for the allergens studied, and demonstrated a close correlation with the diagnosis of inhalant-specific allergy. Our results showed that, for overall allergens, MAST-CLA was lightly less sensitive and more specific than RAST (the two in vitro tests gave an identical overall efficiency). [ABSTRACT FROM AUTHOR]

To obtain further insight into gonadal function, a series of 50 prepubertal patients with β-thalassaemia major (24 boys and 26 girls) aged from 12.6 to 18 years (mean 15 years) who had received a bone marrow transplantation (BMT) during childhood or the peripubertal period, at the age of 3.6-14.5 years (mean 10.8 years), were periodically re-evaluated at intervals of 6-12 months. The last evaluation was done 1-9 years (mean 4.2 years) after BMT. At each examination we measured height, pubertal stage, plasma gonadotrophins (LH and FSH) before and after the GnRH stimulation test (i.v.), sex steroids (total and free testosterone in males, and 17β-oestradiol in females), serum ferritin and bone age. Fourty percent of patients entered or passed through puberty normally despite clinical and hormonal evidence of gonadal dysfunction in most of them. A correlation was not found between the pubertal stage and age at BMT, and no statistical difference between patients who did not enter into puberty and patients with spontaneous pubertal development was found in serum ferritin levels. Our data confirm that gonads in male and female thalassaemic patients are exposed to the cytotoxic effects of the preparative transplant regime with alkylating agents. In some patients absence of pubertal development was due to gonadotrophin insufficiency, probably secondary to previous iron overload. These findings emphasize the need for a vigilant long-term follow up study of thalassaemic patients who have had BMT. [ABSTRACT FROM AUTHOR]