Biomedical subjects

M Hill

Publications and source records attributed to M Hill.

At least 19 recordsLinked to original sources

PubMed2006

Association of C/T polymorphism in the LRP5 gene with circulating follicle stimulating hormone in Caucasian postmenopausal women.

The LRP5 gene is believed to be primarily associated with bone metabolism via Wnt signaling. The latter pathway, however, appears to control various other systems outside the skeleton. To find the relationships of the LRP5 gene to serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) in the cohort of normal postmenopausal women, we identified the C/T (c.4037:A1330V) polymorphism in the LRP5 gene using a restriction analysis of the PCR product in a cohort of 165 untreated pre- and post-menopausal women. In a subset of 111 post-menopausal women we analyzed the association between the LRP5 genotype and serum levels of sex-hormones including FSH and LH. The distribution of CC, TC and TT genotypes of the C/T polymorphism in the whole group was 73.9 %, 23.6 % and 2.4 %, respectively, which is comparable with other Caucasian populations. As no TT homozygote was found in the group of post-menopausal women, serum sex-hormones were compared between CC and TC genotypes. Women with the CT allele combination had markedly higher serum FSH levels as compared to carriers of the CC genotype (p<0.004). No differences between these genotypes were found in serum LH levels as well as the circulating sex-steroids such as estradiol, testosterone, dehydroepiandrosterone and/or its sulphate, androstenedione and SHBG. To conclude, the LRP5 gene is associated with circulating FSH in normal post-menopausal women in the present study. The mediating role of subtle undetectable variations in estrogen levels is discussed. We did not find any relationship between the LRP-5 genotype and serum LH levels.

Aged↗

PubMed2006

Salivary cortisol in low dose (1 microg) ACTH test in healthy women: comparison with serum cortisol.

To date, a single report has appeared on the use of salivary cortisol for adrenal function testing with a low dose ACTH, although 1 microg has become preferred as a more physiological stimulus than the commonly used 250 microg ACTH test. Our present study was aimed to obtain physiological data on changes of free salivary cortisol after 1 microg ACTH stimulation. This approach was compared with the common method based on the changes of total serum cortisol. Intravenous, low-dose ACTH test was performed in 15 healthy women (aged 22-40 years) with normal body weight, not using hormonal contraceptives, in the follicular phase of the menstrual cycle. Blood and saliva for determination of cortisol were collected before ACTH administration and 30 and 60 min after ACTH administration. Basal concentration of salivary cortisol (mean +/- S.E.M., 15.9+/-1.96 nmol/l) increased after 1 microg ACTH to 29.1+/-2.01 nmol/l after 30 min, and to 27.4+/-2.15 nmol/l after 60 min. The differences between basal and stimulated values were highly significant (p<0.0001). The values of salivary cortisol displayed very little interindividual variability (p<0.04) in contrast to total serum cortisol values (p<0.0001) A comparison of areas under the curve (AUC) related to initial values indicated significantly higher AUC values for salivary cortisol than for total serum cortisol (1.89+/-0.88 vs. 1.22+/-0.19, p<0.01). Correlation analysis of serum and salivary cortisol levels showed a borderline relationship between basal levels (r=0.5183, p=0.0525); correlations after stimulation were not significant. Low-dose ACTH administration appeared as a sufficient stimulus for increasing salivary cortisol to a range considered as a normal adrenal functional reserve.

Adrenal Glands↗

PubMed2006

Alpha- and beta-secretase activity as a function of age and beta-amyloid in Down syndrome and normal brain.

Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months-69 years) and in 26 controls (5 months-100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alpha-secretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Abeta) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Abeta degradation and clearance.

Adolescent↗

PubMed2006

Widespread vascular production of C-reactive protein (CRP) and a relationship between serum CRP, plaque CRP and intimal hypertrophy.

OBJECTIVES: Evidence of local vascular production and a relationship between serum hsCRP levels and tissue expression of CRP in subjects with vascular disease would support a direct role for CRP in atherosclerosis. METHODS AND RESULTS: Vascular tissue from subjects undergoing coronary artery bypass grafting surgery (CABGS) (n=28) and carotid endarterectomy (CEA) (n=25) were studied. Histological samples were assessed for intima-media ratio (IMR) and CRP by immunohistochemistry. CRP mRNA was quantified by real-time polymerase chain reaction. CRP mRNA was seen in all plaques, non-atherosclerotic artery and atrium but no difference in mRNA expression was seen between plaque and non-atherosclerotic tissue. Serum hsCRP correlated with IMR (r=0.64, p=0.001) in non-atherosclerotic arteries and with plaque CRP staining (r=0.57, p=0.009) independent of age, BMI, lipids, diabetes and blood pressure. In a separate patient series, serum hsCRP was measured in aortic and coronary sinus blood from subjects undergoing CABGS or angiography (n=54). There was a coronary circulation hsCRP gradient ([mean+/-S.E.M.] aortic CRP 4.3mg/l+/-0.8 versus coronary sinus 5.8+/-1.2mg/l, p<0.05). CONCLUSIONS: Widespread vascular CRP mRNA expression, a correlation between serum hsCRP, intimal hypertrophy and plaque CRP, and a coronary hsCRP gradient suggest vascular secretion may contribute to serum CRP levels.

Aged↗

PubMed2006

Investigation of two-dimensional acoustic resonant modes in a particle separator.

Within an acoustic standing wave particles experience acoustic radiation forces, a phenomenon which is exploited in particle or cell manipulation devices. When developing such devices, one-dimensional acoustic characteristics corresponding to the transducer(s) are typically of most importance and determine the primary radiation forces acting on the particles. However, radiation forces have also been observed to act in the lateral direction, perpendicular to the primary radiation force, forming striated patterns. These lateral forces are due to lateral variations in the acoustic field influenced by the geometry and materials used in the resonator. The ability to control them would present an advantage where their effect is either detrimental or beneficial to the particle manipulation process. The two-dimensional characteristics of an ultrasonic separator device have been modelled within a finite element analysis (FEA) package. The fluid chamber of the device, within which the standing wave is produced, has a width to height ratio of approximately 30:1 and it is across the height that a half-wavelength standing wave is produced to control particle movement. Two-dimensional modal analyses have calculated resonant frequencies which agree well with both the one-dimensional modelling of the device and experimentally measured frequencies. However, these two-dimensional analyses also reveal that these modes exhibit distinctive periodic variations in the acoustic pressure field across the width of the fluid chamber. Such variations lead to lateral radiation forces forming particle bands (striations) and are indicative of enclosure modes. The striation spacings predicted by the FEA simulations for several modes compare well with those measured experimentally for the ultrasonic particle separator device. It is also shown that device geometry and materials control enclosure modes and therefore the strength and characteristics of lateral radiation forces, suggesting the potential use of FEA in designing for the control of enclosure modes in similar particle manipulator devices.

Journal Article↗

PubMed2006

The Eating Inventory, body adiposity and prevalence of diseases in a quota sample of Czech adults.

OBJECTIVE: To study the relationships between the Eating Inventory (EI) factors (restraint, disinhibition and hunger), body adiposity and prevalence of selected diseases in a quota sample of Czech adults. SUBJECTS AND METHODS: The sample included 1429 men and 1624 women who were interviewed individually by trained investigators. The sample was quota representative--for gender, age, size of residential location, region and socioeconomic status in Czech adults. Anthropometric data, socioeconomic and lifestyle information were obtained. Subjects filled out the EI questionnaire. Physicians reported about subjects' morbidity. RESULTS: Backward stepwise regression analysis revealed that restraint and disinhibition were significant predictors of body mass index (BMI) along with gender, age, parental obesity, weight loss attempts, present dieting and educational level. The same factors plus income predicted the waist circumference. BMI and waist circumference were negatively related to restraint but positively to disinhibition. According to logistic regression analysis restraint and disinhibition were significantly associated with hypertension, cardiovascular diseases and hyperlipidaemia. Diabetes was significantly related to restraint and hunger scores. The observed association between EI factors and diseases remained significant even when BMI and age were taken into account. CONCLUSION: As shown in earlier studies, disinhibition was positively and restraint negatively associated with BMI and waist circumference. For the first time, factors of the EI were also identified as significant predictors of diseases characterizing the metabolic syndrome.

Adult↗

PubMed2006

Hormonal homeostasis in a group of 216 aging Czech males and correlation with responses to a questionnaire of the University of St Louis.

UNLABELLED: The male aging process is accompanied by changes in the levels of several types of hormones. Falling levels of androgenic-anabolic steroids (total testosterone, free testosterone, biologically accessible testosterone, dehydroepiandrosterone) correspond to a group of symptoms referred to as PADAM syndrome (Partial Androgen Deficiency in the Aging Male). In the case of those carefully examined patients with symptoms of PADAM and proven hypogonadism, administering androgen supplements can alleviate some of the undesirable manifestations. In its literature, the University of St Louis repeatedly refers to its questionnaire as a verbal tool for the detection of possible hypogonadism. The aim of this study was to ascertain to what extent the aging process is evident in hormonal homeostasis detected in laboratory testing, and the extent to which this data is in accord with the evaluation of responses to questions in the University of St Louis questionnaire. METHOD: 216 men aged over 50 years were examined. Measurements were taken of: testosterone; the index of free testosterone; androstenedione; dihydrotestosterone; dehydroepiandrosterone and its sulfate; isomers 7alpha- and 7beta-hydroxydehydroepiandrosterone; epitestosterone; luteinizing hormone (LH); follicle-stimulating hormone (FSH); prolactin; and sexual hormone-binding globulin (SHBG). Evaluations of the patients' responses to the University of St Louis questionnaire were compared with the results of the laboratory tests. RESULTS: The study confirms that the most prominent phenomenon is that of an age-related decrease in the index of free testosterone, which is indicated in particular by an increase in the level of SHBG, and by a decrease in dehydroepiandrosterone and its derivatives. No significant correlation was found between levels of hormones and single items on the questionnaire, nor with the overall score arrived at by studying the patients' data.

Aged↗

PubMed2006

Management of acute bleeding in a patient with congenital afibrinogenaemia.

Congenital afibrinogenaemia is a rare bleeding disorder characterized by absence of fibrinogen and varying bleeding tendency. Treatment with fibrinogen concentrates is considered to be the best choice for afibrinogenaemic patients who experience bleeding. We report the case of a 22-year-old Greek patient who presented with large muscular haematomas and was treated with fibrinogen concentrates. The efficacy of this treatment and the problems that arose during his hospitalization are being discussed.

Adult↗

PubMed2006

[The volumes of the thyroid gland in adults aged 18-65 years in the Czech Republic--determination of the norms].

OBJECTIVE: In the areas with moderate iodine deficit the sonographic examination of thyroid gland is a precious method of precise determination of its volume. The objective of the work was the sonographic examination of males and females aged 18-65 years and to determine the norms of the volumes of thyroid gland. METHODS AND RESULTS: In total, by random sampling, there were sonographically examined 3 416 adults in 11 areas of the Czech Republic; there was chosen a set of 971 females and 681 males whose iodinuria level in first morning urine sample was equal or higher than 100 microg/l. This set was divided according to sex and into the age categories in 5-year interval. The measurement of 3 dimensions of the thyroid gland was determined by Medison-Kretz SA 600 sonographic device with the use of 7.5 MHz linear probe for the depth and width measurement and 3.5 MHz probe was used for the lengths measurement. The volume was determined for each lobe individually using Brunn's formula: V (ml) = 0.479 x length x depth x width. Our results imply the age-related increase of the volume of thyroid gland at both sexes (F-ratio = 1.99, p < 0.0001). At men and women the volume of thyroid gland fluently increases to the 30th year equally, from 30 years to 55 years it increases more rapidly in men while in women there is observed a moderate plateau. Further increase of the volume of thyroid gland is equally fluent from the age of 55 years. CONCLUSION: We managed to determine first own norms of the volumes of thyroid gland for men and women aged 18-65 years in the Czech Republic in five-year age categories. In terms of practical use we recommend 90th percentile as a limit for the evaluation of upper limit of thyroid gland and the 10th percentile for the evaluation of lower limit of the volume of thyroid gland.

Adolescent↗

PubMed2006

[Is decreased thyroid echogenity a good indicator of thyroid autoimmune disorder?].

INTRODUCTION: Thyroid gland with mildly decreased or significantly decreased echogenity is indicating possible autoimmune disorder even before first symptoms, i.e. change in laboratory tests measuring the level of thyroid hormones and antibodies to thyroid antigens occur. TARGET: to consider changes in thyroid gland echogenity suspecting thyroid autoimmune disorder and to determine antibodies to thyroid antigens in the respective type of thyroid echogenity (increased, normal, mildly decreased or significantly decreased) to consider the activity of autoimmune thyropathies related to echogenity and to compare these factors. METHODS: Echogenity of the thyroid gland was examinated in randomly selected population (n = 1 055, 360 male, 695 female) in 11 regions of the Czech republic, all presented with urinary iodine concentration > 100 microg/L of urine. The echogenity was determined in 4-level scale as increased (1), normal (0), mildly decreased (-1) and significantly decreased (-2). Texture of thyroid was evaluated in 2-level scale as homogenous or non-homogenous. For the evaluation of the relation between echogenity type (1 to -2) and TgAb, and between the type of echogenity and TOPAb frequence analysis (logarithm-linear modules) was used, i.e. the complete module was compared with the measured values. RESULTS: The selected adults (695 female, 360 male) with urinary iodine concentration > 100 microg/L of urine presented with increased echogenity in 2 females (0.28%) and 1 male (0.28%), normal echogenity in 281 females (40.42%) and 206 males (57.22%), mildly decreased echogenity in 288 females (41.43%) and 128 males (35.56%) and significantly decreased echogenity in 124 females (17.84%) and 25 males (6.95%). The biggest group, both in males and in females, presented with normal and mildly decreased echogenity. Homogenous thyroid gland structure was found in 223 females (32.08%) and 220 males (61.11%). Non-homogenous texture was found in 472 females (67.92 %) and 140 males (38.89%). Frequence analysis both in males and in females was focused on: 1. relation between the echogenity (ECHO) and TgAb: in females with positive TgAb (14.23%), significant relation to ECHO can be seen (p < 0,0001), in contradiction to males; 2. relation between the echogenity (ECHO) and TPOAb: this relation is very significant both in males and in females (p < 0.0001); 3. mutual relation between TgAb and TPOAb: both in males and in females very significant (p < 0.0001); positive relation between antibodies can be seen. Positive presence of antibodies can be found less frequent, negative presence of both antibodies is more frequent; 4. relation between the echogenity, TgAb and TPOAb: no statistic significance was found. CONCLUSION: Homogenous thyroid gland structure was mainly found in males and, on the contrary, non-homogenous structure in females. In 52.7% of adults with significantly decreased echogenity, autoimmune disorder was confirmed in laboratory tests at the same time. With echogenity increasing, TgAb and TPOAb decreased, vice versa. Sonography, evaluating decreased echogenity, can be an early indicator of serious thyropathies before function parameters and clinical symptoms appear. Detected risky adults with sonographic signs of autoimmune disorder have to be monitored and respective treatment considered and started at the very first occurence of positive antibodies even if the function is still normal.

Adult↗

PubMed2006

Weight change and androgen levels during contraceptive treatment of women affected by polycystic ovary.

OBJECTIVE: The aim of this study was to investigate the effect of oral contraceptive Diane 35 (ethinylestradiol + cyproteroneacetate EE/CPA) which is widely used in the treatment of PCOS in Europe, on body weight, lipid levels and endocrine parameters in non-obese women with PCOS. SUBJECTS AND METHODS: Nineteen PCOS women were examined in the early follicular phase of menstrual cycle, blood samples for the estimation of cholesterol (C), HDL cholesterol (HDL-C), triglycerides (TG), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were taken before the start of treatment with Diane 35 and again after 7 +/- 3.8 months of treatment with Diane 35. Body weight (W) was recorded at the time of both examinations. RESULTS: After the treatment with Diane 35 the levels of W (p<0.05), total C (p<0.05), TG (p<0.004) and SHBG (p<0.0001) increased significantly. In addition, significant negative correlation between SHBG levels before treatment and increase of W after Diane 35 was found (r= -0.56; p<0.02). Increase of W correlated negatively with T before treatment (r= 0.58; p< .02) and positively with the change in T level after treatment (r=0.50; p<0.05). CONCLUSIONS: Increase of body weight in a significant number of PCOS-affected women was seen after treatment with Diane 35 and it is assumed to blunt ameliorating effects of this treatment on androgen levels. Considering our findings, we conclude that the treatment with CPA/EE can result in significant weight gain ameliorating positive effects of the treatment on androgen levels. These findings could underline the necessity of the finding new therapeutical options for PCOS, besides contraception. Studies concerning body composition during contraceptive treatment in PCOS would be also useful in the future.

Adult↗

PubMed2005

Circulating neuroactive C21- and C19-steroids in young men before and after ejaculation.

Twelve neuroactive and neuroprotective steroids, androgens and androgen precursors i.e. 3alpha,17beta-dihydroxy-5alpha-androstane, 3alpha-hydroxy-5alpha-androstan-17-one, 3alpha-hydroxy-5beta-androstan-17-one, androst-5-ene-3beta,17beta-diol, 3beta,17alpha-dihydroxy-pregn-5-en-20-one (17alpha-hydroxy-pregnenolone), 3beta-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA), testosterone, androst-4-ene-3,17-dione (androstenedione), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), 3beta-hydroxy-pregn-5-en-20-one (pregnenolone), 7alpha-hydroxy-DHEA, and 7beta-hydroxy-DHEA were measured using the GC-MS system in young men before and after ejaculation provoked by masturbation. The circulating level of 17alpha-hydroxypregnenolone increased significantly, whereas the other circulating steroids were not changed at all. This fact speaks against the hypothesis that a drop in the level of neuroactive steroids, e.g. allopregnanolone may trigger the orgasm-related increase of oxytocin, reported by other authors.

17-alpha-Hydroxypregnenolone↗

PubMed2005

Metabolic syndrome in young Czech women with polycystic ovary syndrome.

METHODS: Sixty-nine young women with polycystic ovary syndrome (PCOS) [age 25.2+/- 4.7 years, with body mass index (BMI) 24.3 +/- 4.8 kg/m2; mean 6 SD] and 73 age-matched healthy females (BMI 22.3 +/- 3.3 kg/m2; mean +/- SD) were evaluated for the occurrence of features of metabolic syndrome according to the Adult Treatment Panel III. RESULTS: Overt metabolic syndrome (the presence of three and more risk factors) was not more common in PCOS women (1/64, 1.6%) than in healthy controls (0/73, 0%). On the other hand, in nearly 50% of PCOS women isolated features of metabolic syndrome, most often a decrease in high-density lipoprotein (HDL) cholesterol, were found. Women with at least one feature of metabolic syndrome were, in comparison with women without any of these features, significantly more obese (P = 0.0001), with lower insulin sensitivity (P = 0.05). When comparing PCOS women according to the degree of insulin sensitivity, as determined by euglycaemic clamp, isolated features of metabolic syndrome were found in 8/17 women above the upper quartile, compared with 11/16 women below the lower quartile of insulin sensitivity (P = 0.20). CONCLUSIONS: Overt metabolic syndrome is only rarely encountered in young Czech females affected by PCOS but its isolated features are relatively frequent, both in young PCOS patients and in age-matched control women.

Adult↗

PubMed2005

Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF.

The purpose of the study was to establish the optimal dose of capecitabine (X) to be used within a multicentre, randomised study evaluating the potential roles of oxaliplatin (O) and X in chemonaive patients (pts) with advanced oesophagogastric cancer. Two by two design was used, and pts were randomised to one of four regimens and stratified for extent of disease, performance status (PS) and centre. The treatment regimens are epirubicin, cisplatin, 5-fluorouracil (ECF), EOF, ECX or EOX. Doses: E 50 mg m(-2), C 60 mg m(-2) and O 130 mg m(-2) i.v. 3 weekly; F 200 mg m(-2) day(-1) i.v. and X 500 mg m(-2) b.i.d.(-1) (escalated to 625 mg m(-2) b.i.d.(-1) after results of first interim analysis) p.o., continuously. First interim analysis was performed when 80 pts had been randomised. Dose-limiting fluoropyrimidine toxicities were stomatitis, palmar plantar erythema (PPE) and diarrhoea; 5.1% of X-treated pts experienced grade 3/4 toxicity. Protocol planned dose escalation of X to 625 mg m(-2) b.i.d.(-1) was instituted and a second interim analysis has been performed; results are presented in this paper. A total of 204 pts were randomised at the time of the protocol planned 2nd interim analysis. Grade 3/4 fluoropyrimidine-related toxicity was seen in 13.7% pts receiving F, 8.4% pts receiving X 500 mg m(-2) b.i.d.(-1) and 14.7% pts receiving X 625 mg m(-2) b.i.d.(-1). Combined complete and partial response rates were ECF 31% (95% CI 18.7-46.3), EOF 39% (95% CI 25.9-53.1), ECX 35% (95% CI 21.4-50.3), EOX 48% (95% CI 33.3-62.8). Grade 3/4 fluoropyrimidine toxicity affected 14.7% of pts treated with X 625 mg m(-2) b.i.d.(-1), which is similar to that observed with F, confirming this to be the optimal dose. The replacement of C by O and F by X does not appear to impair efficacy. The trial continues to total accrual of 1000 pts.

Administration, Oral↗

PubMed2005

How short-term transdermal treatment of men with 7-oxo-dehydroepiandrosterone influence thyroid function.

Dehydroepiandrosterone may influence thyroid function. Its metabolite, 7-oxo-dehydroepiandrosterone, a precursor of immunomodulatory 7-hydroxylated metabolites and thermogenic agent, belongs to candidates of steroid replacement therapy. The question was addressed whether its application does influence laboratory parameters of thyroid function. 7-Oxo-dehydroepiandrosterone in the form of emulgel, 25 mg/day, was applied transdermally to 21 healthy men for 8 consecutive days. Morning blood was collected before the treatment (Day 0, Stage 1), during treatment (Day 5, Stage 2), on the first day after the last administration (Day 9, Stage 3), one week (Day 16, Stage 4), and 9 weeks (Day 72, Stage 5) after treatment termination. The levels of thyrotropin, free thyroxine and triiodothyronine, dehydroepiandrosterone, its sulfate and its 7-hydroxyepimers were measured. The changes were evaluated by analysis of variance and correlation analysis. During treatment a significant rise of 7beta-hydroxy-dehydroepiandrosterone was observed, which persisted 1 week after treatment termination. No changes were observed in dehydroepiandrosterone and its sulfate. Though a slight but significant rise of TSH and of both thyroid hormones occurred during treatment, its levels soon returned to the basal values. It was concluded that treatment of 7-oxo-dehydroepiandrosterone affects the thyroid parameters only temporarily and that it provides a considerable persistent amount of 7beta-hydroxy-dehydroepiandrosterone.

Administration, Cutaneous↗

PubMed2005

The influence of n-3 polyunsaturated fatty acids and very low calorie diet during a short-term weight reducing regimen on weight loss and serum fatty acid composition in severely obese women.

Polyunsaturated fatty acids of n-3 series (n-3 PUFA) were shown to increase basal fat oxidation in humans. The aim of the study was to compare the effect of n-3 PUFA added to a very low calorie diet (VLCD), with VLCD only during three-week inpatient weight reduction. Twenty severely obese women were randomly assigned to VLCD with n-3 PUFA or with placebo. Fatty acids in serum lipid fractions were quantified by gas chromatography. Differences between the groups were determined using ANOVA. Higher weight (7.55+/-1.77 vs. 6.07+/-2.16 kg, NS), BMI (2.82+/-0.62 vs. 2.22+/-0.74, p<0.05) and hip circumference losses (4.8+/-1.81 vs. 2.5+/-2.51 cm, p<0.05) were found in the n-3 group as compared to the control group. Significantly higher increase in beta-hydroxybutyrate was found in the n-3 group showing higher ketogenesis and possible higher fatty acid oxidation. The increase in beta-hydroxybutyrate significantly correlated with the increase in serum phospholipid arachidonic acid (20:4n-6; r = 0.91, p<0.001). In the n-3 group significantly higher increase was found in n-3 PUFA (eicosapentaenoic acid, 20:5n-3, docosahexaenoic acid, 22:6n-3) in triglycerides and phospholipids. The significant decrease of palmitoleic acid (16:1n-7) and vaccenic acid (18:1n-7) in triglycerides probably reflected lower lipogenesis. A significant negative correlation between BMI change and phospholipid docosahexaenoic acid change was found (r = -0.595, p<0.008). The results suggest that long chain n-3 PUFA enhance weight loss in obese females treated by VLCD. Docosahexaenoate (22:6n-3) seems to be the active component.

3-Hydroxybutyric Acid↗

PubMed2005

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma.

There is currently no standard salvage chemotherapy regimen in relapsed and refractory lymphoma. Gemcitabine is a novel nucleoside analogue, which acts synergistically with cisplatin both in vitro and in clinical studies. We evaluated the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) in 41 heavily pretreated patients with relapsed and refractory Hodgkin's and non-Hodgkin's lymphoma. The best-achieved response rate (RR) was 79% (95% CI 64-91), with a complete RR of 21%. In patients with chemo-resistant disease, the RR was 63%. Myelosuppression was the main toxicity, the incidence of Grade 3 or 4 anaemia, neutropenia and thrombocytopenia was 17.1, 61.0 and 53.7% respectively. Only one patient had neutropenic sepsis and none of the patients suffered from haemorrhage. Grade 3 or 4 nonhaematological toxicity was minimal and stem cell mobilisation was not inhibited. GEM-P is an effective salvage regimen and its use prior to autologous stem cell transplant warrants further investigation.

Adolescent↗

PubMed2005

A randomised comparison between 6 months of bolus fluorouracil/leucovorin and 12 weeks of protracted venous infusion fluorouracil as adjuvant treatment in colorectal cancer.

BACKGROUND: We performed a multicentre randomised trial to compare the efficacy and toxicity of 12 weeks of protracted venous infusion (PVI) 5-fluorouracil (5-FU) against the standard bolus monthly regimen of 5-FU/leucovorin (LV) given for 6 months as adjuvant treatment in colorectal cancer (CRC). PATIENTS AND METHODS: Patients with curatively resected stage II and III CRC were randomly assigned to 5-FU/LV [5-FU 425 mg/m(2) intravenously (i.v.) and LV 20 mg/m(2) i.v. bolus days 1-5 every 28 days for 6 months] or to PVI 5-FU (300 mg/m(2)/day for 12 weeks). RESULTS: Between 1993 and 2003, 801 eligible patients were randomised to 5-FU/LV (n=404) or PVI 5-FU (n=397). With a median follow-up of 5.3 years, 231 relapses and 220 deaths have been observed. Five-year relapse-free survival (RFS) was 66.7% [95% confidence interval (CI) 61.6% to 71.3%] and 73.3% (95% CI 68.4% to 77.6%) with bolus 5-FU/LV and PVI 5-FU, respectively [hazard ratio (HR) 0.8; 95% CI 0.62-1.04; P=0.10]. Five-year overall survival (OS) was 71.5% (95% CI 66.4% to 75.9%) and 75.7% (95% CI 70.8% to 79.9%) with bolus 5-FU/LV and PVI 5-FU, respectively (HR 0.79; 95% CI 0.61-1.03; P=0.083). There was a significant survival advantage for patients starting adjuvant chemotherapy within 8 weeks (P=0.044). Significantly less diarrhoea, stomatitis, nausea and vomiting, alopecia, lethargy, and neutropenia (all with P <0.0001) were seen with PVI 5-FU. CONCLUSIONS: There was no OS difference between the two arms, although PVI 5-FU was associated with a trend towards better RFS and OS compared with bolus 5-FU/LV, as well as significantly less toxicity. Based on our results, the probability of 12 weeks of PVI 5-FU being inferior to 6 months of bolus 5-FU/LV is extremely low (P <0.005), and therefore shorter duration of adjuvant treatment should be explored further.

Adult↗