Room-temperature ferromagnetic nanotubes controlled by electron or hole doping.

Nanotubes and nanowires with both elemental (carbon or silicon) and multi-element compositions (such as compound semiconductors or oxides), and exhibiting electronic properties ranging from metallic to semiconducting, are being extensively investigated for use in device structures designed to control electron charge. However, another important degree of freedom--electron spin, the control of which underlies the operation of 'spintronic' devices--has been much less explored. This is probably due to the relative paucity of nanometre-scale ferromagnetic building blocks (in which electron spins are naturally aligned) from which spin-polarized electrons can be injected. Here we describe nanotubes of vanadium oxide (VO(x)), formed by controllable self-assembly, that are ferromagnetic at room temperature. The as-formed nanotubes are transformed from spin-frustrated semiconductors to ferromagnets by doping with either electrons or holes, potentially offering a route to spin control in nanotube-based heterostructures.

Spin-dependent tunneling in self-assembled cobalt-nanocrystal superlattices.

Self-assembled devices composed of periodic arrays of 10-nanometer-diameter cobalt nanocrystals display spin-dependent electron transport. Current-voltage characteristics are well described by single-electron tunneling in a uniform array. At temperatures below 20 kelvin, device magnetoresistance ratios are on the order of 10%, approaching the maximum predicted for ensembles of cobalt islands with randomly oriented preferred magnetic axes. Low-energy spin-flip scattering suppresses magnetoresistance with increasing temperature and bias-voltage.

The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes.

OBJECTIVE: To describe the systematic analysis of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes, characterise the structural chromosome rearrangements, map the translocation breakpoints, and report detectable genomic imbalances. METHODS: DNA microarrays were used with a resolution of 1 Mb for the detailed genome-wide analysis of the patients. Array CGH was used to screen for genomic imbalance and array painting to map chromosome breakpoints rapidly. These two methods facilitate rapid analysis of translocation breakpoints and screening for cryptic chromosome imbalance. Breakpoints of rearrangements were further refined (to the level of spanning clones) using fluorescence in situ hybridisation where appropriate. RESULTS: Unexpected additional complexity or genome imbalance was found in six of 10 patients studied. The patients could be grouped according to the general nature of the karyotype rearrangement as follows: (A) three cases with complex multiple rearrangements including deletions, inversions, and insertions at or near one or both breakpoints; (B) three cases in which, while the translocations appeared to be balanced, microarray analysis identified previously unrecognised imbalance on chromosomes unrelated to the translocation; (C) four cases in which the translocation breakpoints appeared simple and balanced at the resolution used. CONCLUSIONS: This high level of unexpected rearrangement complexity, if generally confirmed in the study of further patients, will have an impact on current diagnostic investigations of this type and provides an argument for the more widespread adoption of microarray analysis or other high resolution genome-wide screens for chromosome imbalance and rearrangement.

Protection of metabolic and exercise capacity in unselected weight-losing cancer patients following treatment with recombinant erythropoietin: a randomized prospective study.

This study was aimed at evaluating whether anemia could be prevented in unselected weight-losing cancer patients on anti-inflammatory treatment by early and prophylactic treatment with recombinant human erythropoietin (rhEPO) and whether such a benefit could be translated into improved physical function and metabolic efficiency. One hundred eight cancer patients who experienced progressive cachexia due to solid, mainly gastrointestinal tumors were randomized to receive twice daily a cyclo-oxygenase inhibitor (controls; indomethacin, 50 mg twice a day) or indomethacin and erythropoietin, provided on individual basis to prevent development of progressive anemia (study patients; indomethacin, 50 mg twice a day plus rhEPO; range, 12,000-30,000 units per week). All patients were treated and followed up until death or to preterminal stage. Biochemical tests (blood, liver, kidney, and thyroid), nutritional state assessment (food intake and body composition), and exercise testing with simultaneous measurements of respiratory gas exchanges before and during exercise were performed before institution of treatments and then at regular intervals during the treatment period (2-30 months after start). Study and control patients did not differ in survival. rhEPO prevented development of anemia during the entire observation period. This was associated with a significantly more preserved maximum exercise capacity in study patients compared to control patients during the follow-up period (101 +/- 10 versus 66 +/- 6 W; P < 0.0001), based on more effective ventilation and whole-body respiratory gas exchanges. These improvements were also evident when exercise performance was normalized to lean body mass, an indirect measure of the skeletal muscle mass. The metabolic efficiency, expressed as oxygen uptake per watt produced, was also significantly preserved in rhEPO-treated patients compared to controls (14.1 +/- 1.1 versus 16.3 +/- 0.9 ml O2/W, P < 0.05). Our results demonstrate that institution of early and prophylactic rhEPO treatment to patients with progressive cancer prevents development of tumor-induced anemia. This achievement was associated with a better preserved exercise capacity, which is explained in part by improved whole-body metabolic and energy efficiency during work load.

Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors.

Eicosanoids may be important factors for tumor cell proliferation, metastatic formation, and development of cancer cachexia. The present study has evaluated the effect of anti-inflammatory treatment on tumor progression in clinical cancer. Patients (n = 135) with insidious or overt malnutrition due to generalized malignancy (various kinds of solid tumors) and an expected survival of more than 6 months were randomized by a computer-based algorithm to receive placebo, prednisolone (10 mg twice daily), or indomethacin (50 mg twice daily) p.o. until death. Patient groups were stratified in the randomization procedure for sex, tumor type, stage, nutritional state, and previous tumor treatment, and biochemical, physiological, and some functional variables (Karnowsky index, fatigue and pain score). A majority of these variables was then registered during the follow-up. Indomethacin and prednisolone treatment maintained Karnowsky index, while placebo-treated patients experienced a decreased index. Indomethacin-treated patients suffered less pain and consumed less additional analgetics compared to the other patient groups. Indomethacin prolonged mean survival compared to placebo-treated patients from 250 +/- 28 days to 510 +/- 28 days (P < 0.05). Survival analysis on observations from all patients treated with either indomethacin or prednisolone demonstrated a significantly prolonged survival by anti-inflammatory treatment compared to placebo treatment (log rank, P < 0.03). The results suggest that not only may prostaglandin synthesis inhibition offer palliative support to patients with solid advanced cancer, but it may also impact on pathways that ultimately determine outcome.

Jejunal permeability and hepatic extraction of fluvastatin in humans.

OBJECTIVES: The primary objective was to investigate the effective permeability and the hepatic extraction of fluvastatin, a new 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, during a jejunal perfusion in humans. The secondary objective was to investigate the relationship between human jejunal effective permeability values and physicochemical properties for four different drugs. METHODS: Nine healthy male volunteers were included in the study, which consisted of two sequential study parts. In the first part, the jejunal effective permeability of fluvastatin, antipyrine, metoprolol, and atenolol was assessed with use of the regional jejunal perfusion approach (150 minutes, 2.0 ml/min). After a washout period of at least 5 days, the same subjects received an intravenous infusion of fluvastatin (20 minutes, 2.0 mg). Plasma samples were taken in both parts of the study and were analyzed for the content of fluvastatin. RESULTS: The mean hepatic extraction of fluvastatin was 67% after the jejunal perfusion and 73% after the intravenous infusion. The half-life of fluvastatin was approximately 60 minutes after both administration routes. The jejunal effective permeability and the fraction absorbed both correlated (r2 = 0.968, p < 0.05; and r2 = 0.994, p < 0.05) with the partition coefficient (log D, pH 6.5) but not with the molecular size or the hydrogen bond number. CONCLUSION: Fluvastatin is extracted by the liver to a large extent (about 70%) and has a short half-life after both oral and intravenous administration. In this study, the human jejunal effective permeability and the fraction absorbed for these four drugs were better predicted by log D (pH 6.5) than both the molecular size and the hydrogen bond number.

The effect of indomethacin on food and water intake, motor activity and survival in tumour-bearing rats.

This investigation has addressed the question whether food and water intake, motor activity and tumour growth are influenced by indomethacin in experimental cancer. Growing rats implanted with a methylcholanthrene-induced sarcoma were studied in metabolic cages connected to a computer. Food intake, water consumption and motor activity were continuously recorded over 30 days following tumour implantation. Treated tumour-bearing animals received indomethacin 1.0 mg/kg per day in drinking water. Food intake declined early in untreated tumour-bearing animals, but water intake was not affected. Motor activity decreased in untreated tumour-bearing animals from days 16-17 onward. Indomethacin treatment prolonged survival and 40% of these tumour-bearers were 'complete responders'. In some animals tumour growth was only marginally affected, but survival was still significantly improved ('partial responders'). Food intake was significantly improved in complete responders. Thus this positive effect seen in complete responders was secondary to less active tumour growth. Motor activity was also significantly higher in responders compared with non-responders.

Elevated energy expenditure in cancer patients with solid tumours.

Cancer patients (n = 106) and non-cancer subjects (n = 96) were classified as weight stable (n = 70) or weight-losing (n = 132). Cancer patients had elevated resting energy expenditure (REE) compared with either weight-losing (23.6 [0.4] vs. 20.5 [0.5] kcal/kg per day, P less than 0.001) or weight-stable controls (22.0 [0.6] vs. 17.9 [0.4], P less than 0.001). Cancer patients had increased fat oxidation irrespective of weight loss (1.24 [0.07] vs. 0.87 [0.04] mg/kg per min; 1.07 [0.04] vs. 0.78 [0.04], P less than 0.001). Elevated energy expenditure was counter-regulated by a decrease in thyroid hormones. Abnormal liver function had no impact on REE in either group. Heart rate was the most powerful factor for prediction of high energy expenditure in both patients and controls. Elevated energy expenditure was related to the increased heart rate in cancer patients in a significantly higher proportion than that in controls. Increased metabolic rate is a significant component behind weight loss in cancer disease, independent of malnutrition and an elevated adrenergic state may be a likely explanation.

Beta-adrenoceptor activity and resting energy metabolism in weight losing cancer patients.

This study was aimed at comparing the blocking of beta-adrenoceptor activity to changes in the resting energy metabolism of 10 cancer patients with progressive weight loss due to solid malignant tumours. Resting energy expenditure (REE) as well as whole body carbohydrate and fat oxidation were investigated and related to plasma substrate levels (glucose, glycerol, free fatty acids (FFA)) before and after 5 days of oral administration of specific beta1 receptor blocker (atenolol, 50 mg/day) and non-specific beta1,beta2-adrenoceptor (propranolol, 80 mg/day) blockade. The administration order of the drugs was random, and a 3-day washout period was used in all individuals between the provision of the first and the second drug in order to minimise the risk of carry-over effects. Resting measurements in the morning after an overnight fast were performed by indirect calorimetry. Atenolol treatment reduced REE by 77+/-14 kcal/day and propranolol by 48+/-13 kcal/day, respectively (P<0.05 versus pretreatment values). Whole body oxygen uptake and carbon dioxide production were decreased similarly by both atenolol and propranolol treatment (P<0.05). Carbohydrate oxidation was increased by atenolol and decreased by propranolol, whilst fat oxidation was decreased by atenolol and unchanged by propranolol. The decrease in REE, accounting for the decline in heart rate, was significantly more pronounced following treatment with propranolol compared with atenolol (P<0.05). Atenolol and propranolol had no effect on blood glucose, plasma glycerol and FFA. We conclude that wastage in cancer patients is in part explained by increased beta(1) and beta(2)-adrenoceptor activity, in part secondary to elevated cardiovascular activity as a result of anaemia, loss of cardiac contractile capacity and altered host metabolism.

Tracheopathia osteoplastica: clinical, radiologic, and pathological correlations.

The clinical, radiologic, and pathological features of tracheopathia osteoplastica are reviewed and three new cases are reported. Tracheopathia osteoplastica is usually not diagnosed until autopsy. However, it may be a surprise finding to the endoscopist and occasionally it may produce signs and symptoms of upper airway obstruction and enter into the differential diagnosis of a tumor of the trachea. The chest radiograph may permit the correct clinical diagnosis to be made. The pathological diagnosis is easy with adequate tissue. Because tracheopathia is a lesion predominantly of old age with little associated morbidity or mortality, the correct clinical diagnosis will prevent unnecessary operation.

Fibrous histiocytoma of the trachea.

The light and electron microscopic features of a fibrous histiocytoma of the trachea that occurred in a 15-year-old Caucasian girl are presented. Emphasis is placed on the aggresive behavior and the importance of early recognition of the lesion in an unusual location.

Evaluation of the effect of sodium selenate on the growth of mycobacterial stock cultures.

A study was undertaken to evaluate the effect of sodium selenate supplementation (5 micrograms/mL) on the growth characteristics of a variety of mycobacterial isolates. Supplemented Lowenstein-Jensen and Middlebrook 7H11 agar were compared to nonsupplemented media. Eighteen mycobacterium stock isolates were tested. Selenate supplementation had no predictable or consistent growth stimulatory effect as compared with nonsupplemented media.

Prevalence of carnitine depletion in critically ill patients with undernutrition.

The aim of this study was to evaluate to what extent secondary carnitine deficiency may exist based on the prevalence of subnormal carnitine status in patients with critical illness and abnormal nutritional state. Healthy control patients (n = 12) were investigated and compared with patients with possible secondary carnitine deficiency, ie, patients with overt severe protein-energy malnutrition (PEM, n = 28), postoperative long-term (greater than 14 days) parenteral glucose feeding (250 g glucose/d, n = 7), severe liver disease (n = 10), renal insufficiency (n = 7), and sustained septicemia with increased metabolic rate (n = 8). Nutritional status, energy expenditure, creatinine excretion, and blood biochemical tests were measured in relationship to free and total carnitine concentrations in plasma and skeletal muscle tissue, as well as urinary excretion of free and total carnitine. The overall mortality rate was 48% within 30 days of the investigation in study patients with the highest mortality in liver disease (90%). The hospitalization range was 14 to 129 days in study patients. Most study patients had lost weight (4% to 19%) and had abnormal body composition. Patients with liver disease, septicemia, renal insufficiency, and those on long-term glucose feeding had significantly higher than predicted metabolic rate (+25% +/- 3%), while patients with severe malnutrition had decreased metabolic rate compared with controls. Patients with liver disease had increased plasma concentrations of free (96 +/- 16 mumol/L) and total (144 +/- 27 mumol/L) carnitine compared with controls (45 +/- 3, 58 +/- 7 mumol/L, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma of the endometrium in pregnancy.

Adenocarcinoma of the endometrium with intrauterine pregnancy is extremely rare. This report presents the finding of an adenoacanthoma of the endometrium discovered during therapeutic abortion and compares it with 6 other cases previously published. Four of the 7 tumors were adenocanthomas, a neoplasm that accounts for 20-30% of endometrial adenocarcinoma in the general population. Follow-up on 4 of the 6 previously reported patients indicates that 3 are well more than 5 years after diagnosis. The 1 patient who died of disease had an adenoacanthoma and was the only patient with extensive myometrial invasion at hysterectomy. The patient described in the present report is well 2 1/2 years after hysterectomy.

Predicting discharge destination for patients with severe motor stroke: important functional tasks.

Many patients with severe stroke are capable of returning to the community after receiving rehabilitation services. The purpose of this study was to describe outcomes of patients with stroke in FIM-FRG STR1, a classification based on the Functional Independence Measure, and identify important functional tasks associated with discharge to home. FIM-FRG STR1 is one of nine subpopulations of stroke that have been identified based on motor/cognitive FIM subscale score and age. We reviewed the program evaluation data of 259 cases of stroke from 1993 to 1996. We performed a descriptive analysis of the data and a logistic regression analysis to determine which tasks measured by the FIM were associated with discharge destination, a key indicator of rehabilitation success. We found that three admission FIM variables (bladder management, toilet transfers, memory) and three discharge FIM variables (upper body dressing, bed/chair transfers, comprehension) were associated with discharge destination with up to 75% accuracy. The implications of these findings are discussed.

Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study.

BACKGROUND AND AIMS: Serum levels of gastrin-17 (S-G-17) and pepsinogen I (S-PGI) are biomarkers of gastric antral and corpus mucosa, respectively. In a prospective multicentre investigation, we determined whether these tests, together with the assay of Helicobacter pylori antibodies, are a non-endoscopic tool for the diagnosis of atrophic gastritis. MATERIALS AND METHODS: The series comprised 404 consecutive adult outpatients undergoing diagnostic upper-gastrointestinal endoscopy for various dyspeptic symptoms in five outpatient clinics. Gastric biopsies from the antrum and corpus (at least two biopsies from both sites) were available from all patients, and they were evaluated according to the guidelines of the updated Sydney system. S-PGI and S-G-17 were assayed with ELISA methods using monoclonal antibodies to pepsinogen I and amidated gastrin-17. In addition to the fasting level (S-G-17(fast)), a postprandial S-G-17 (S-G-17(prand)) level was measured 20 min after ingestion of a protein-rich drink. H. pylori antibodies were determined using a polyclonal EIA method. RESULTS: S-G-17(prand) (and S-G-17(fast)) and S-PGI levels decreased with increasing grade of atrophy of the antrum or corpus, respectively. S-G-17(prand) levels were significantly lower in patients with advanced (moderate or severe) atrophic antral H. pylori gastritis than in those with non-atrophic H. pylori gastritis. All patients with a resected antrum demonstrated S-G-17(prand) levels that were almost undetectable. Of the nine patients with an H. pylori-positive moderate or severe atrophic antral gastritis, six had S-G-17(prand) levels below 5 pmol/l. Similarly, S-PGI levels were significantly lower in patients with advanced corpus atrophy than in those without. Of the 45 patients with moderate or severe corpus atrophy in endoscopic biopsies, 35 patients had S-PGI levels < 25 microg/l. By using the cut-off levels for S-G-17(prand) and S-PGI with the best discrimination, the sensitivity and specificity of the blood test panel in delineation of patients with advanced atrophic gastritis (either in the antrum or the corpus, or both) were 83% and 95%, respectively. The predictive values of the positive and negative test results were 75% and 97%, respectively. In the diagnosis of atrophic gastritis, the application of S-G-17(fast) showed a slightly lower sensitivity and specificity than the application of S-G-17(prand) as a biomarker for antral atrophy. CONCLUSIONS: The diagnosis of atrophic gastritis obtained with the blood test panel of S-G-17, S-PGI and H. pylori antibodies is in good agreement with the endoscopic and biopsy findings. The panel is a tool for non-endoscopic diagnosis and screening of atrophic gastritis.

The effect on energy and nitrogen metabolism by continuous, bolus, or sequential infusion of a defined total parenteral nutrition formulation in patients after major surgical procedures.

BACKGROUND: The role of IV infusion kinetics to explain nutrition efficiency was investigated in patients after major surgical procedures. METHODS: IV nutrition was provided as three different infusion kinetic regimens in a randomized fashion. All patients received nonprotein calories (100% of predicted preoperative REE, 60% D-glucose, 40% fat) and amino acid nitrogen (0.2 g N/d). Group A: Nutrition was provided by sequential infusion with combined fat and amino acids during daytime and glucose alone during nighttime ("sequential infusion"). Group B: Patients received 24-hour combined infusion with fat, amino acids, and glucose (all in one mixture) ("continuous infusion"). Group C: Nutrition was provided by bolus infusions during 1 hour followed by 2 hours without any infusion ("bolus infusion"). RESULTS: The daily energy balance was negative in all groups (-318 +/- 25 kcal/d, sequential infusion; -368 +/- 25 kcal/d continuous infusion; -292 +/- 20 kcal/d, bolus infusion). Significantly different excretion patterns of nitrogen in urine occurred among the groups despite an almost identical provision of nitrogen. Continuously infused patients retained nitrogen significantly better (-0.2 +/- 0.6 g/d) compared with sequentially (-3.4 +/- 1.0 g/d) and bolus-infused patients (-2.8 +/- 0.3 g/d) (p < .01), whereas their cumulative urinary glucose excretion was significantly larger. Continuously infused patients were in cumulative nitrogen balance during the entire postoperative period, whereas the other groups were in a significantly negative nitrogen balance. Urinary 3-methylhistidine excretion was similar in all groups. CONCLUSIONS: The breakdown of muscle proteins was not sensitive to alterations in nutrient and substrate supply. Thus improved nitrogen retention reflected entirely improved synthesis. "All-in-one" IV nutrition with prolonged infusion periods is at present the most favorable regimen considering both the nutritional efficiency and its metabolic load on the organism after major surgery.

Structured triglycerides were well tolerated and induced increased whole body fat oxidation compared with long-chain triglycerides in postoperative patients.

BACKGROUND: It has been proposed, on the basis of animal experiments, that medium-chain triglycerides (MCT) may exert more favorable effects on whole body metabolism of injured animals than long-chain triglycerides (LCT). Therefore, the present study was designed to evaluate whether structured triglycerides are associated with increased whole body fat oxidation without promotion of ketogenesis in postoperative patients. METHODS: A structured lipid emulsion (73403 Pharmacia, Sweden) containing medium- and long-chain fatty acids, esterified randomly to glycerol in a triglyceride structure, was used. Whole body fat oxidation was determined by indirect calorimetry in the postoperative period. Patients were randomized to receive structured lipids 1 day followed by LCT (Intralipid, Pharmacia) the next day or vice versa during 6 postoperative days. In part 1 of the study patients received fat at 1.0 g/kg per day in the presence of 80% of the basal requirement of nonprotein calories. In part 2 patients received fat at 1.5 g/kg per day in the presence of 120% of the nonprotein caloric requirement. Amino acids were always provided at 0.15 g N/kg per day. RESULTS: Structured lipids were not associated with any side effects, were rapidly cleared from the plasma compartment, and were rapidly oxidized without any significant hyperlipidemia or ketosis. Provision of structured lipids in the presence of excess of nonprotein calories (part 2) caused a significantly higher whole body fat oxidation (2.4 +/- 0.05 g/kg per day) compared with LCT provision (1.9 +/- 0.06 g/kg per day) (p < .0001) examined in the same patients. CONCLUSIONS: The results demonstrated for the first time in man that provision of structured triglycerides were associated with increased whole body fat oxidation in stressed postoperative patients, which is in line with the original metabolic and biochemical concept for structured triglycerides. The study provided evidence to support that structured lipids may represent a next generation of IV fat emulsions that may be clinically advantageous compared with conventional LCT emulsions in certain clinical conditions.

Structured triglycerides to postoperative patients: a safety and tolerance study.

Long-chain triglycerides are still the standard in fat emulsions, although medium-chain triglycerides have been suggested to have metabolic advantages even though pure medium-chain triglycerides are toxic in large doses. The next generation of fat emulsions may be structured triglycerides, which are assumed to provide a higher oxidation rate, faster clearance from blood, improved nitrogen sparing, and less of a tendency to accumulate in the reticuloendothelial system compared with long-chain triglyceride emulsions. This study was designed to evaluate the safety and tolerance of structured triglyceride fat emulsion 73403 (Kabi Pharmacia Parenterals, Stockholm, Sweden) compared with that of a standard long-chain triglyceride emulsion (Intralipid 20%) in postoperative patients requiring total parenteral nutrition after major surgery. The study was randomized and of the double-blind, parallel group type. Twenty patients were included and treated for 5 to 7 days. Safety and tolerance variables demonstrated no major differences between the study and control groups. Physiologic and biochemical variables suggested that structured lipids were rapidly cleared and metabolized. This study represents the first report of administration of structured triglycerides to postoperative patients. The structured triglyceride emulsion (73403) demonstrated no difference in safety and tolerance compared with Intralipid 20%. Therefore, it will now be possible to follow up with studies on metabolic efficiencies of structured triglycerides in postoperative patients.