Patient Preparation and Radiation Protection Guidance for Adult Patients Undergoing Radioiodine Treatment for Thyroid Cancer in the UK.

Radioactive iodine is a highly effective treatment for thyroid cancer and has now been used in clinical practice for more than 80 years. In general, the treatment is well tolerated. However, it can be logistically quite complex for patients due to the need to reduce iodine intake and achieve high levels of thyroid-stimulating hormone prior to treatment. Radiation protection precautions must also be taken to protect others from unnecessary radiation exposure following treatment. It has been well documented by thyroid cancer patient support groups that there is significant variation in practice across the UK. It is clear that some patients are being asked to observe unnecessarily burdensome restrictions that make it more difficult for them to tolerate the treatment. At the instigation of these support groups, a multidisciplinary group was assembled to examine the evidence and generate guidance on best practice for the preparation of patients for this treatment and the management of subsequent radiation protection precautions, with a focus on personalising the advice given to individual patients. The guidance includes advice about managing particularly challenging situations, for example treating patients who require haemodialysis. We have also worked together to produce a patient information leaflet covering these issues. We hope that the guidance document and patient information leaflet will assist centres in improving our patients' experience of receiving radioactive iodine. The patient information sheet is available as Supplementary Material to this article.

Auditory Oddball Responses Across the Schizophrenia-Bipolar Spectrum and Their Relationship to Cognitive and Clinical Features.

OBJECTIVE: Neural activations during auditory oddball tasks may be endophenotypes for psychosis and bipolar disorder. The authors investigated oddball neural deviations that discriminate multiple diagnostic groups across the schizophrenia-bipolar spectrum (schizophrenia, schizoaffective disorder, psychotic bipolar disorder, and nonpsychotic bipolar disorder) and clarified their relationship to clinical and cognitive features. METHODS: Auditory oddball responses to standard and target tones from 64 sensor EEG recordings were compared across patients with psychosis (total N=597; schizophrenia, N=225; schizoaffective disorder, N=201; bipolar disorder with psychosis, N=171), patients with bipolar disorder without psychosis (N=66), and healthy comparison subjects (N=415) from the second iteration of the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP2) study. EEG activity was analyzed in voltage and in the time-frequency domain (low, beta, and gamma bands). Event-related potentials (ERPs) were compared with those from an independent sample collected during the first iteration of B-SNIP (B-SNIP1; healthy subjects, N=211; psychosis group, N=526) to establish the repeatability of complex oddball ERPs across multiple psychosis syndromes (r values >0.94 between B-SNIP1 and B-SNIP2). RESULTS: Twenty-six EEG features differentiated the groups; they were used in discriminant and correlational analyses. EEG variables from the N100, P300, and low-frequency ranges separated the groups along a diagnostic continuum from healthy to bipolar disorder with psychosis/bipolar disorder without psychosis to schizoaffective disorder/schizophrenia and were strongly related to general cognitive function (r=0.91). P50 responses to standard trials and early beta/gamma frequency responses separated the bipolar disorder without psychosis group from the bipolar disorder with psychosis group. P200, N200, and late beta/gamma frequency responses separated the two bipolar disorder groups from the other groups. CONCLUSIONS: Neural deviations during auditory processing are related to psychosis history and bipolar disorder. There is a powerful transdiagnostic relationship between severity of these neural deviations and general cognitive performance. These results have implications for understanding the neurobiology of clinical syndromes across the schizophrenia-bipolar spectrum that may have an impact on future biomarker research.

Schizophrenia Exhibits Bi-directional Brain-Wide Alterations in Cortico-Striato-Cerebellar Circuits.

Distributed neural dysconnectivity is considered a hallmark feature of schizophrenia (SCZ), yet a tension exists between studies pinpointing focal disruptions versus those implicating brain-wide disturbances. The cerebellum and the striatum communicate reciprocally with the thalamus and cortex through monosynaptic and polysynaptic connections, forming cortico-striatal-thalamic-cerebellar (CSTC) functional pathways that may be sensitive to brain-wide dysconnectivity in SCZ. It remains unknown if the same pattern of alterations persists across CSTC systems, or if specific alterations exist along key functional elements of these networks. We characterized connectivity along major functional CSTC subdivisions using resting-state functional magnetic resonance imaging in 159 chronic patients and 162 matched controls. Associative CSTC subdivisions revealed consistent brain-wide bi-directional alterations in patients, marked by hyper-connectivity with sensory-motor cortices and hypo-connectivity with association cortex. Focusing on the cerebellar and striatal components, we validate the effects using data-driven k-means clustering of voxel-wise dysconnectivity and support vector machine classifiers. We replicate these results in an independent sample of 202 controls and 145 patients, additionally demonstrating that these neural effects relate to cognitive performance across subjects. Taken together, these results from complementary approaches implicate a consistent motif of brain-wide alterations in CSTC systems in SCZ, calling into question accounts of exclusively focal functional disturbances.

Bioelectric impedance vector analysis (BIVA) in hospitalised children; predictors and associations with clinical outcomes.

BACKGROUND: Clinical use of bioelectric impedance is limited by variability in hydration. Analysis of raw bioelectric impedance vectors (BIVA), resistance (R), reactance (Xc) and phase angle (PA) may be an alternative for monitoring disease progression/treatment. Clinical experience of BIVA in children is limited. We investigated predictors of BIVA and their ability to predict clinical outcomes in children with complex diagnoses. METHODS: R, Xc and PA were measured (BODYSTAT Quadscan 4000) on admission in 108 patients (4.6-16.8 years, mean 10.0). R and Xc were indexed by height (H) and BIVA-SDS for age and sex calculated using data from healthy children. Potential predictors and clinical outcomes (greater-than-expected length-of-stay (LOS), complications) were recorded. RESULTS: Mean R/H-SDS was significantly higher (0.99 (SD 1.32)) and PA-SDS lower (-1.22 (1.68))) than expected, with a wide range for all parameters. In multivariate models, the Strongkids risk category predicted R/H-SDS (adjusted mean for low, medium and high risk = 0.49, 1.28, 2.17, p = 0.009) and PA-SDS (adjusted mean -0.52, -1.53, -2.36, p = 0.01). BIVA-SDS were not significantly different in patients with or without adverse outcomes. CONCLUSIONS: These complex patients had abnormal mean BIVA-SDS suggestive of reduced hydration and poor cellular health according to conventional interpretation. R/H-SDS was higher and PA-SDS lower in those classified as higher malnutrition risk by the StrongKids tool. Further investigation in specific patient groups, including those with acute fluid shifts and using disease-specific outcomes, may better define the clinical role of BIV.

Trends in vaccine investment in middle income countries.

Although a proven and effective preventive health measure, childhood immunization programs remain vulnerable to budgetary pressures. Sustainable financing of immunization programs is an important issue that presents a challenge for middle-income countries (MIC) in particular, in part due to technological advances meaning more vaccines are available. This study aimed to analyse trends in immunization program investment across 15 MIC selected based on availability of data, income level classification, and regional representativeness. We assessed investment trends in relation to vaccine coverage, vaccine access, and broader health indicators. Immunization and expenditure data were obtained from the World Health Organisation (WHO) database and the WHO UNICEF Joint Reporting Form and WHO Vaccine Product, Price and Procurement from 2006-2016. We calculated a weighted average index of vaccine commitment (WAIVC) based on vaccine coverage, vaccine scope, and weighted by vaccine innovation measured by approximating vaccine expenditure. Correlation analyses were conducted between immunization expenditure per-capita and each WAIVC, infant mortality and life expectancy. Correlation analyses at a global and individual country level indicate an improvement in immunization access, vaccination commitment measured by WAIVC, and scope of available vaccines in countries with sustained increases in vaccination funding. Increases in national immunization expenditure were correlated with reduced infant mortality and increased life expectancy. Vaccine expenditure comprises a small proportion (less than 2%) of total healthcare spending and has not uniformly increased in accordance with the scope of available vaccines. The present analysis supports the premise that countries with consistent increases in vaccine expenditure have increased vaccine coverage and commitment measured by WAIVC and improved broader health outcomes, indicating the value of sustained investment in vaccination for improved population health. The benefits of vaccine expenditure in this holistic fashion are critical to inform policy decisions on national budget allocation for vaccine funding.

Comparison of liver function with two new/mixed intravenous lipid emulsions in children with intestinal failure.

BACKGROUND/OBJECTIVE: The high incidence of liver disease associated with intravenous soybean lipid has led to development and use of alternative intravenous lipid emulsions (ILEs). The aim of this study was to compare two new/mixed ILEs: a medium-chain triglyceride (MCT) combined with soybean (i.e., Lipofundin) and a combination of both these lipids with additional olive and fish oils (SMOF). SUBJECTS/METHODS: Neonates/premature infants newly starting parenteral nutrition (PN) treatment and children with abnormal liver function tests, alanine transferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γ-GT) 1.5x upper limit of normal and/or total bilirubin >50 µmol/l for >2 weeks on treatment with PN containing pure soybean ILE (Intralipid 20%; Fresenius Kabi), were started on/changed to either SMOF or Lipofundin. RESULTS of biochemistry and clinical outcome were compared on commencing and discontinuing treatment according to the new ILE used. RESULTS: One hundred and twenty-seven children aged 0-16 (median 0.6) years were included. Fifity-six were given Lipofundin and 71 SMOF. Fifty-three of 127 started PN for the first time and 74 had had previous treatment with Intralipid. During treatment, ALT and ALP levels fell significantly (P<0.008 on SMOF; P<0.05 on Lipofundin), with additional significant reduction in γ-GT with SMOF. Hyperbilirubinaemia incidence decreased from 34% on starting to 24% on discontinuing treatment (P⩽0.05). Infection rate/1000 catheter days, full blood count, serum triglyceride and cholesterol levels were similar with both ILEs. CONCLUSION: Addition of MCT to soybean ILE was associated with improved liver function. There was an even greater improvement when olive and fish oils were also added with higher incidence of resolution of abnormal liver function tests and reduced inflammation.

Effect of narrowband ultraviolet B phototherapy on melanocytic naevi.

BACKGROUND: Melanocytic naevi have been observed to undergo morphological changes following exposure to narrowband ultraviolet (NB-UV)B radiation. OBJECTIVES: To analyse changes in naevi exposed to NB-UVB in a large cohort of patients. METHODS: Subjects referred for phototherapy had macroscopic and dermoscopic images taken of prominent melanocytic naevi at the following time points: immediately prior to NB-UVB treatment, after 10 exposures, after 30 exposures or at the end of treatment if earlier, and 3 months after discontinuing treatment. Four dermatologists, by consensus, examined each naevus for specific clinical and dermoscopic features at each time point. The size (area) of each naevus was determined by plenimetry. RESULTS: Complete sets of images were taken for 36 out of 51 patients. The most common global dermoscopic patterns in the 440 naevi examined were reticular (50%) and globular (32%). Following NB-UVB exposure, blurring or merging of lines was observed in 45% of reticular naevi. An increase in colour intensity and in the number of dots or globules was observed in 63% of globular naevi, and 167 naevi (40%) underwent a change in size. Of these, 91/167 (54%) decreased in size, with a median area reduction of 8% (0·9-42%); while 76/167 (46%) increased in size, with a median area increase of 9% (1-76%). CONCLUSIONS: Around half of naevi exposed to a course of NB-UVB treatment undergo size or morphological changes. Naevi that enlarged tended to revert to pretreatment size 3 months after discontinuation of phototherapy.

Association between granulomatous colitis in French Bulldogs and invasive Escherichia coli and response to fluoroquinolone antimicrobials.

BACKGROUND: French Bulldogs develop a form of granulomatous colitis (GC) with histopathological resemblance to GC of Boxer dogs (GCB). GCB is associated with mucosally invasive Escherichia coli whose eradication correlates with clinical remission. HYPOTHESIS/OBJECTIVES: To characterize the clinical and histopathological features, presence or absence of invasive colonic bacteria, and response to fluoroquinolones in French Bulldogs with GC. ANIMALS: A total of 6 French Bulldogs with a histological diagnosis of GC. METHODS: Retrospective study of medical records. Bacterial colonization was evaluated using 16S rRNA probes for eubacteria and E. coli. Biopsy specimens from 3 dogs were cultured for bacteria. Clinical response to fluoroquinolone antimicrobials was determined. RESULTS: All dogs were ≤1 year of age with hematochezia that was refractory to empirical therapy. Clinicopathologic and fecal analysis did not reveal abnormalities. Abdominal ultrasound revealed patchy thickening of the colon in 4/5 dogs and regional lymphadenopathy in 5/5. Colonoscopic abnormalities included irregularly thickened and ulcerated mucosa, hyperemia, and overt bleeding in 4/6 cases. Multifocal accumulations of PAS-positive macrophages and intramucosal E. coli were present in colonic biopsies of all 6 dogs. Administration of enrofloxacin (5/6) or marbofloxacin (1/6) at 4.4-10 mg/kg (median 10 mg/kg) PO q24h for 6-10 weeks was associated with clinical improvement within 5-14 days. All dogs remained in remission over a 3-30 month follow-up period. CONCLUSIONS: Granulomatous colitis in young French Bulldogs is associated with the presence of invasive E. coli and closely parallels GCB. Treatment with fluoroquinolone antimicrobials can induce lasting clinical remission.

The addition of cottonseed hulls to the starter and supplementation of live yeast or mannanoligosaccharide in the milk for young calves.

The objectives of this study were to investigate the effects of the addition of cottonseed hulls (CSH) to the starter and the supplementation of live yeast product (YST) or mannanoligosaccharide product (MOS) to milk, on growth, intake, rumen development, and health parameters in young calves. Holstein (n = 116) and Jersey (n = 46) bull (n = 74) and heifer (n = 88) calves were assigned randomly within sex at birth to treatments. All calves were fed 3.8 L of colostrum daily for the first 2 d. Holstein calves were fed 3.8 L of whole milk, and Jersey calves were fed 2.8 L of whole milk through weaning at 42 d. Calves continued on trial through 63 d. Six treatments were arranged as a 2 x 3 factorial. Calves received either a corn-soybean meal-based starter (21% crude protein and 6% acid detergent fiber; -CSH) or a blend of 85% corn-soybean meal-based starter and 15% CSH (18% crude protein and 14% acid detergent fiber; +CSH) ad libitum. In addition, calves received whole milk with either no supplement (NONE) or supplemented with 3 g/d of mannanoligosaccharide product (MOS) or 4 g/d of live yeast product (YST) through weaning at 42 d. Twelve Holstein steers [n = 6 (per starter type); n = 4 (per supplement type)] were euthanized for collection and examination of rumen tissue samples. Dry matter intake (DMI) was greater for Holstein calves fed +CSH (0.90 kg/d) than -CSH (0.76 kg/d). Final body weight at 63 d of Holstein calves fed +CSH (75.8 kg) was greater than that of those fed -CSH (71.0 kg). Average daily gain (ADG) was greater for Holstein calves fed +CSH (0.58 kg/d) than -CSH (0.52 kg/d). However, Holstein calves fed -CSH had a greater feed efficiency (FE; 0.71 kg of ADG/kg of DMI) than those fed +CSH (0.65 kg of ADG/kg of DMI). Also, Holstein calves fed +CSH had narrower rumen papillae (0.32 mm) compared with those fed -CSH (0.41 mm). There were no significant effects of CSH on DMI, ADG, or FE in Jersey calves. There were no significant effects of YST or MOS on DMI, ADG, FE, or rumen papillae measures in Holstein calves. Jersey calves fed YST or MOS had greater final body weight at 63 d (51.2 kg and 51.0 kg, respectively) than calves fed NONE (47.5 kg). However, there were no significant effects of YST or MOS on DMI, ADG, or FE in Jersey calves.

Effects of milk replacer composition on growth, body composition, and nutrient excretion in preweaned Holstein heifers.

Twenty-four newborn Holstein heifer calves were fed 1 of 4 milk replacers (MR): control (20% CP, 21% fat; MR fed at 441 g/d); high protein/low fat (HPLF; 28% CP, 20% fat; MR fed at 951 g/d); high protein/high fat (HPHF; 27% CP, 28% fat; MR fed at 951 g/d); and HPHF MR fed at a higher rate (HPHF+; 27% CP, 28% fat; MR fed at 1,431 g/d). Dry calf starter (20% CP, 1.43% fat) composed of ground corn (44.4%), 48% CP soybean meal (44.4%), cottonseed hulls (11.2%), and molasses (1.0%) was offered free choice. Heifers were obtained from a commercial dairy, blocked by groups of 8 in the order acquired, and randomly assigned to treatments within group. Upon arrival at the research farm, heifers were fed the control for 2 feedings. Treatments were imposed when heifers were 4 +/- 1 d of age. Heifers were on study for 61 +/- 1 d. Body weight and body size measures were taken weekly. Four-day total collection of feed refusals, feces, and urine was initiated at 57 +/- 1 d of age. Heifers were slaughtered at the end of the collection period to evaluate body composition. Preplanned contrasts were used to compare control to all, HPLF to HPHF, and HPHF to HPHF+. Heifers fed the control diet consumed more starter than those fed other treatment diets, but their total dry matter intake and apparent dry matter digestibility were lowest. Fecal output was highest in heifers fed the control diet, whereas urine output and urine N excretion were lowest. Nitrogen intake and urine N excretion were greater for heifers fed HPHF+ compared with HPHF but were not affected by MR fat content (HPLF vs. HPHF). Retention (g/d) of N and P was greater in heifers fed all nutrient-dense diets compared with those fed the control diet, but was not improved by increasing fat in the milk replacer (HPLF vs. HPHF) or by increasing the amount fed. Addition of fat to the milk replacer (HPLF vs. HPHF) increased empty body weight fat content without improving average daily gain or frame measures. Increasing the volume fed (HPHF vs. HPHF+) increased growth rate and empty body weight, but HPHF+ heifers were neither taller nor longer and their carcasses contained more fat. Clear improvements in growth and nutrient retention were observed with more nutrient-dense diets, but most of the improvements were seen with the increased protein intake relative to the control MR; adding fat to the high protein MR did not further improve lean tissue gain.

A model of phosphorus digestion and metabolism in the lactating dairy cow.

A dynamic, mechanistic, compartmental model of phosphorus (P) digestion and metabolism was constructed in the Advanced Continuous Simulation Language using conservation of mass principles and mass action kinetics. Phosphorus was assumed to exist in 3 forms: inorganic (Pi), phytic acid (Pp), and organic (excluding phytic acid; Po). All 3 forms were assumed to be present in the digestive tract with absorption of Pi into blood. Inputs to the model were total P intake; Pp, Po, and Pi as proportions of total P; milk yield; rate of salivation (fixed at 239 L/d); and rate of liquid passage from the rumen (fixed at 198 L/d). The model was fitted to 2 experiments from the literature. Derived parameters were well defined by the data. With a mean observed P intake of 75 g/d, total tract P digestibility was 38%. Phytic acid P digestibility in the rumen was 74%, with no additional Pp digestion in the lower tract. Inorganic P and Po digestibility in the lower tract were 48 and 89%, respectively. Flows of Po and Pi from the rumen were 2.4 and 3.0 times greater than intake, respectively. The increase in Po was apparently due to microbial growth. The increase in Pi arose primarily from secretion of Pi into the rumen via salivation where 65% of absorbed P was recycled to the rumen. Milk synthesis used 30% of absorbed Pi, and 1% was excreted in urine. This research suggested that the primary regulation points for maintaining blood P were bone deposition and resorption and absorption from the intestine. However, because bone P balance was related to both dietary P intake and ruminal phytase activity, it is critical to achieve a better understanding of phytate digestibility across several feeds if dietary P is to be reduced below current requirements.

Nitrogen and phosphorus retention and excretion in late-gestation dairy heifers.

The objectives of this study were to evaluate the effects of limit feeding diets containing concentrates or by-products in place of forages on manure and nutrient excretion in growing, gravid heifers. Eighteen Holstein heifers confirmed pregnant were grouped by due date and fed 1 of 3 diets (n = 6 per treatment) for the last 14 wk of pregnancy. Diets were high forage, fed ad libitum (HF); by-product based (BP), fed at the same rate as HF-fed heifers; or low forage (LF), fed at 86% of the HF diet. Diets were designed to supply equal quantities of P, N, and metabolizable energy. Total collection of feces and urine was conducted in wk 14, 10, 6, and 2 prepartum. The HF ration was 90.7% forage, 13.7% crude protein (CP), and contained orchardgrass hay, corn silage, corn grain, soybean meal 44%, and a vitamin-mineral premix. The BP diet was 46.2% forage and 14.0% CP, with 70% of the grain mix space replaced with soybean hulls and cottonseed hulls in a 1:1 ratio, with intake limited to 93% of the dry matter intake (DMI) of HF. The LF ration was 45.3% forage and 17.8% CP, with intake limited to 86% of the DMI of HF. The effect of diet was analyzed with repeated measures, using preplanned contrasts to compare HF with BP and LF with HF and BP. As designed, heifers fed HF and BP had greater DMI than the heifers limit-fed LF, and there was no effect of diet on average daily gain or BW. Intake and digestibility of N were lower, and fecal N excretion was higher, in heifers fed HF and BP than heifers fed LF. Mean feces excretion on both a wet and dry basis was greater for HF heifers compared with BP heifers and less for LF heifers than for HF and BP heifers. Despite differences in urinary output, diet had no effect on urea N excretion, but there was a trend for heifers fed HF and BP rations to excrete less urinary N compared with those fed LF. Compared with HF and BP heifers, LF heifers tended to have lower fecal P excretion and had higher urinary P excretion. Measured manure and urine excretion from heifers fed LF was greater than current American Society of Agricultural and Biological Engineers values, whereas heifers fed HF excreted less manure and urine than predicted. Heifers achieving similar rates of gain from diets differing in forage, grain, and by-product content excreted widely varying quantities of manure.

Manure nutrient excretion by lactating cows fed exogenous phytase and cellulase.

The effect of an exogenous phytase and cellulase-containing enzyme formulation on nutrient digestibility and excretion was evaluated in 24 Holstein cows. Cows were fed corn silage- and alfalfa silage-based diets with or without a cellulase-phytase blend for 31 d in a continuous random design. Treatment groups were balanced for parity, days in milk, and mature-equivalent projected milk yield. Diets contained 37% forage, 18.3% crude protein, 35.4% neutral detergent fiber, 18% acid detergent fiber, and 0.42% P (no supplemental P). Cows were fed once daily in Calan doors and milked 2 times daily. Body weight and milk yield were recorded at each milking. Milk samples were collected on d 28 to 31 at 8 consecutive milkings. On d 28 to 31, fecal grab samples were collected every 8 h, with sampling times advanced by 2 h each day. Feces samples were pooled by cow. Feed and feces samples were analyzed for acid detergent lignin (used as an internal marker) and for N, P, neutral detergent fiber, and acid detergent fiber. Days in milk were similar between treatments, and body weight and milk yield were unaffected by treatment. Cows fed the enzyme formulation had reduced fecal dry matter, neutral detergent fiber, and acid detergent fiber excretion and reduced fecal excretion of N and P. Apparent digestibility of dry matter, acid detergent fiber, neutral detergent fiber, and N tended to increase with the enzyme formulation. Addition of an exogenous phytase and cellulase enzyme formulation to diets for lactating cows reduced fecal nutrient excretion.

Treatment of active Crohn's disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial.

BACKGROUND AND AIMS: Total enteral nutrition (TEN) with a liquid formula can suppress gut inflammation and induce remission in active Crohn's disease. The mechanism is obscure. Studies have suggested that long term nutritional supplementation with a liquid formula (partial enteral nutrition (PEN)) may also suppress inflammation and prevent relapse. The aim of this study was to compare PEN with conventional TEN in active Crohn's disease. PATIENTS AND METHODS: Fifty children with a paediatric Crohn's disease activity index (PCDAI)>20 were randomly assigned to receive 50% (PEN) or 100% (TEN) of their energy requirement as elemental formula for six weeks. The PEN group was encouraged to eat an unrestricted diet while those receiving TEN were not allowed to eat. The primary outcome was achievement of remission (PCDAI<10). Secondary analyses of changes in erythrocyte sedimentation rate (ESR), C reactive protein, albumin, and platelets were performed to look for evidence of anti-inflammatory effects. RESULTS: Remission rate with PEN was lower than with TEN (15% v 42%; p=0.035). Although PCDAI fell in both groups (p=0.001 for both), the reduction was greater with TEN (p=0.005). Moreover, the fall in PCDAI with PEN was due to symptomatic and nutritional benefits. With both treatments there were significant improvements in relation to abdominal pain, "sense of wellbeing", and nutritional status. However, only TEN led to a reduction in diarrhoea (p=0.02), an increase in haemoglobin and albumin, and a fall in platelets and ESR. CONCLUSIONS: TEN suppresses inflammation in active Crohn's disease but PEN does not. This suggests that long term nutritional supplementation, although beneficial to some patients, is unlikely to suppress inflammation and so prevent disease relapse.

Exercise training and inspiratory muscle training in patients with bronchiectasis.

BACKGROUND: Bronchiectasis is a chronic suppurative lung disease often characterised by airflow obstruction and hyperinflation, and leading to decreased exercise tolerance and reduced health status. The role of pulmonary rehabilitation (PR) and inspiratory muscle training (IMT) has not been investigated in this group of patients. METHODS: Thirty two patients with idiopathic bronchiectasis were randomly allocated to one of three groups: PR plus sham IMT (PR-SHAM), PR plus targeted IMT (PR-IMT), or control. All patients (except the control group) underwent an 8 week training programme of either PR or PR plus targeted IMT. Exercise training during PR was performed three times weekly at 80% of the peak heart rate. IMT was performed at home for 15 minutes twice daily over the 8 week period. RESULTS: PR-SHAM and PR-IMT resulted in significant increases in the incremental shuttle walking test of 96.7 metres (95% confidence interval (CI) 59.6 to 133.7) and 124.5 metres (95% CI 63.2 to 185.9), respectively, and in endurance exercise capacity of 174.9% (95% CI 34.7 to 426.1) and 205.7% (95% CI 31.6 to 310.6). There were no statistically significant differences in the improvements in exercise between the two groups. Significant improvements in inspiratory muscle strength were also observed both in the PR-IMT group (21.4 cm H2O increase, 95% CI 9.3 to 33.4; p = 0.008) and the PR-SHAM group (12.0 cm H2O increase, 95% CI 1.1 to 22.9; p = 0.04), the magnitude of which were also similar (p = 0.220). Improvements in exercise capacity were maintained in the PR-IMT group 3 months after training, but not in the PR-SHAM group. CONCLUSION: PR is effective in improving exercise tolerance in bronchiectasis but there is no additional advantage of simultaneous IMT. IMT may, however, be important in the longevity of the training effects.

Weight and body composition changes during and after adjuvant chemotherapy in women with breast cancer.

Uncontrolled trials have reported significant weight gain in women with breast cancer during treatment with adjuvant chemotherapy. We prospectively evaluated body composition before (visit 1), immediately after (visit 2), and 6 months after (visit 3) chemotherapy in 20 women with stages I-IIIA breast cancer [body mass index (BMI): 24.1 +/- 3.9 kg/m(2)]. We compared their weight change to 51 age- and BMI-matched healthy controls (BMI: 25.5 +/- 3.8 kg/m(2)). In women with breast cancer, there was no weight change from visit 1-2, or from visit 1-3, but weight increased from visit 2-3 (+1.09 +/- 2.46 kg; P = 0.05). Weight change was not different from controls during either interval. In the breast cancer group, the percentage of body fat assessed by air displacement plethysmography increased, and fat-free mass decreased from visit 1-2 (+2.3 +/- 4% and -2.2 +/- 4%; P = 0.02) and from visit 1-3 (+4.0 +/- 6% and -3.8 +/- 6%; P = 0.01). By dual energy x-ray absorptiometry, the percentage of body fat increased from visit 2-3 (+0.9 +/- 1.6%; P = 0.02). Bone mineral content decreased from visit 2-3 (-0.02 +/- 0.04 kg; P = 0.02) and from visit 1-3 (-0.04 +/- 0.06 kg; P = 0.005). By computed tomography, the visceral adipose to sc adipose tissue ratio decreased from visit 1-3 (-0.02 +/- 0.05 ml; P = 0.02). We conclude that, compared with controls, women with breast cancer receiving modern adjuvant chemotherapy regimens show no significant changes in weight during the first year of their treatment. They do, however, appear to undergo unfavorable changes in body composition.

Tumor prevention by 9-cis-retinoic acid in the N-nitroso-N-methylurea model of mammary carcinogenesis is potentiated by the pineal hormone melatonin.

Our laboratory has demonstrated that treatment of MCF-7 breast cancer cells with melatonin (Mlt) followed 24h later with physiological concentrations of all-trans retinoic acid (atRA) results in apoptosis. These studies were extended into trials using the N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model. Initial studies conducted by feeding the animals 9-cis-retinoic acid (9cRA in the chow) and administering melatonin by subcutaneous injection in the late afternoon demonstrated that the combination of Mlt and 9cRA was able to significantly prevent tumor development, and that the combination was more efficacious that either Mlt or 9cRA alone. In this report, we conducted studies to determine if lower doses of 9cRA could be used in combination with Mlt while still maintaining anti-tumor activity and if the route of administration of 9cRA (bolus (gavage) v.s. chronic (chow) routes) affected its interaction with Mlt. The studies presented here demonstrate that significantly reduced doses of 9cRA can be used in combination with Mlt while maintaining anti-tumor efficacy. Furthermore, our studies demonstrate that 9cRA is equally effective when it is administered chronically (chow) or as a bolus (gavage). These data demonstrate that the combined use of Mlt and 9cRA produces additive or synergistic effects, which are more efficacious than 9cRA alone. This combination of Mlt and 9cRA could be a potentially useful clinical treatment regimen for breast cancer since it allows the use of lower doses of retinoic acid, thus, avoiding the toxic side effects associated with the use of high dose retinoids.

Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells.

We have previously demonstrated that the pineal hormone, melatonin, can inhibit the growth of estrogen receptor-alpha (ERalpha)-positive breast cancer cells and suppress ERalpha gene transcription. To investigate the relationship between the estrogen response pathway and melatonin's growth inhibition, ERalpha-positive MCF-7 human breast cancer cells were transiently transfected with an estrogen response element (ERE) luciferase reporter construct and then treated with melatonin (10(-9)-10(-6) M) for 30 min followed by 10(-9) M 17-beta-estradiol (E2) or treated with each compound alone. Melatonin pre-treatment significantly reduced E2-induced ERalpha transactivation and ERalpha-ERE binding activity. We also conducted experiments to determine if melatonin modulates cAMP levels in MCF-7 cells. Melatonin inhibited the forskolin-induced and E2-induced elevation of cAMP levels by 57 and 45%, respectively. These data indicate that melatonin can act as a biological modifier to affect ERalpha transcriptional activity by regulating signal transduction pathways which impinge on the ERalpha and by altering E2-mediated ERalpha transactivation and ERalpha DNA binding activity.

Organisation of the external region of the starch granule as determined by infrared spectroscopy.

Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) was used to study the external regions of starch granules. Native starches (wheat, potato, maize, waxy maize and amylomaize) were analysed and compared to gelatinised and acid-hydrolysed starches. The IR spectra of potato and amylomaize starches were closer to that of highly ordered acid-hydrolysed starch than the other starches. FTIR was not able to differentiate between A- and B-type crystallinity so the difference observed between starches was not related to this factor. The variation between starch varieties was interpreted in terms of the level of ordered structure present on the edge of starch granules with potato and amylomaize being more ordered on their outer regions. This could explain the high resistance of both these starches to enzyme hydrolysis.

The susceptibility of tumors to the antivascular drug combretastatin A4 phosphate correlates with vascular permeability.

The acute effects of the antivascular drug, combretastatin A4 phosphate, on tumor energy status and perfusion were assessed using magnetic resonance imaging (MRI) and spectroscopy. Localized (31)P magnetic resonance spectroscopy showed that LoVo and RIF-1 tumors responded well to drug treatment, with significant increases in the P(i)/nucleoside triphosphate ratio within 3 h, whereas SaS, SaF, and HT29 tumors did not respond to the same extent. This variable response was also seen in MRI experiments in which tumor perfusion was assessed by monitoring the kinetics of inflow of the contrast agent, gadolinium diethylenetriaminepentaacetate. These data were analyzed to give the initial rate and time constant for inflow of contrast agent and the integral under the inflow curve. The differential susceptibility of the tumors to combretastatin A4 phosphate showed a positive correlation with prior MRI measurements of tumor vascular permeability, which was determined by measuring the inflow of a macromolecular contrast agent, BSA-gadolinium diethylenetriaminepentaacetate.