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1.
Ned Tijdschr Geneeskd ; 1632019 11 21.
Article in Dutch | MEDLINE | ID: mdl-31769631

ABSTRACT

A 35-year-old woman developed acute swallowing problems caused by a big oral blood blister after eating nuts. The blister ruptured 32 hours later and healed without scarring. 'Angina bullosa haemorrhagica' was diagnosed after ruling out bleeding disorders.


Subject(s)
Blister/etiology , Gastrointestinal Hemorrhage/etiology , Mouth Diseases/diagnosis , Mouth Diseases/etiology , Oral Hemorrhage/etiology , Adult , Blister/diagnosis , Edema/etiology , Face , Female , Gastrointestinal Hemorrhage/diagnosis , Humans , Mouth Mucosa/pathology
2.
Neth J Med ; 73(6): 284-9, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26228193

ABSTRACT

BACKGROUND: There is limited evidence to support cytotoxic therapy in patients with IgA nephropathy and renal insufficiency. We studied the effect of cytotoxic therapy in patients with IgA nephropathy and renal insufficiency, and evaluated possible predictors of response. METHODS: Retrospective analysis of patients with IgA nephropathy who received immunosuppressive therapy. The primary outcome measure was progression of renal disease, defined as an increase in serum creatinine levels of ≥ 50% or development of end-stage renal disease. RESULTS: From 1996 to 2008, 19 patients with biopsy-proven IgA nephropathy were treated with cytotoxic agents and prednisone because of renal insufficiency and÷ or severe proteinuria. Characteristics of patients at the start of therapy: age 42±11 years, serum creatinine 208 (96-490) µmol÷l, estimated glomerular filtration rate (eGFR) 33 (12-65) ml÷min÷1.73 m2, and protein- creatinine ratio 3.8 (0.6-18.2) g÷10 mmol. Follow-up after initiation of therapy was 35 (7-133) months. Ten patients had progressive renal disease, whereas eGFR was stable in nine. Serum creatinine levels and proteinuria at the start of treatment were not significantly different between responders and non- responders. Proteinuria response at six months after start of therapy proved a good predictor: proteinuria decreased by ≥ 50% and÷or reached levels below 1 g÷day in 8÷9 responders. In contrast, proteinuria decreased by more than 50% and reached levels < 1 g÷day in only 3÷10 non-responders (p < 0.01). CONCLUSION: Prolonged immunosuppressive therapy with cytotoxic agents and prednisone may benefit a subgroup of patients with progressive IgA nephropathy. A reduction of proteinuria ≥ 50% to levels below 1 g÷day within six months predicts a favourable long-term response.


Subject(s)
Glomerulonephritis, IGA/therapy , Immunosuppression Therapy/methods , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/prevention & control , Adult , Disease Progression , Female , Follow-Up Studies , Glomerular Filtration Rate , Glomerulonephritis, IGA/complications , Glomerulonephritis, IGA/physiopathology , Humans , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/physiopathology , Male , Retrospective Studies , Time Factors , Treatment Outcome
3.
Int J Obes (Lond) ; 39(2): 361-7, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25081363

ABSTRACT

BACKGROUND/OBJECTIVES: We have previously shown that 500 ml of a foamed drink ('foam') significantly improved appetite versus a non-foamed control. The objectives of this research were to assess the effect of smaller volumes of foams on appetite, and the potential benefits of foam ingestion and its timing on appetite measures in a reduced-energy context. SUBJECTS/METHODS: Two randomized, parallel design studies (pre- and main study) were conducted using healthy adult subjects. Pre-study: 133 subjects (age 18-50 years, body mass index (BMI) 20-32 kg m(-2)) each consumed either 10, 25, 50, 100, 150 or 250 ml foamed meal replacer (~0.2 kcal ml(-1)), 150 min after a fixed breakfast. Main study: four groups of subjects (n=134; age 18-60 years, BMI 22.5-35.0 kg m(-2)) consumed 200 ml/22 kcal foam (based on pre-study results) immediately after main meals (M), after snacks (S), in-between snacks and main meals (I) or not at all (control, C) within 1 day of a reduced-energy meal plan consisting of three main meals and three snacks. Measurements included self-reported appetite (six scales, reported as area under the curve (AUC)) and (main study only) end-of-day appetite questionnaire. RESULTS: Pre-study: the strongest effect on appetite was produced by 250 ml (consistent across scales), whereas 150 ml showed more pronounced effects than 100 and 50 ml in most scales. Volumes 10 and 25 ml had no effects on any scale. Main study: 200 ml foam reduced appetite AUC substantially in all treatments, particularly M (for example, hunger AUC reduced by 35% (P <0.001), 28% (P <0.05) and 20% (P=0.11) for M, S and I, respectively versus C). A strong reduction in 'appetite for a snack' was seen for all timings (all P <0.05). The end-of-day appetite ratings confirmed these findings. CONCLUSIONS: Modest amounts of a low-energy foam can reduce appetite measures during a 1-day reduced-energy meal plan.


Subject(s)
Appetite/physiology , Beverages , Diet, Reducing/methods , Energy Intake , Hunger/physiology , Satiety Response/physiology , Adult , Appetite Regulation , Area Under Curve , Feeding Behavior , Female , Healthy Volunteers , Humans , Male , Middle Aged , Postprandial Period
4.
Eur J Clin Nutr ; 65(1): 47-54, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20842170

ABSTRACT

BACKGROUND/OBJECTIVES: 'Slowly digestible' carbohydrates have been claimed to reduce appetite through their effects on postprandial glucose and insulin levels, but literature is inconsistent. The inconsistencies between studies might be explained by factors other than glycemic effects per se, for example, nutritional or physical properties. We tested this possibility by examining postprandial glucose, insulin and appetite responses to drinks differing only in rate and extent of digestibility of carbohydrates. This was accomplished by comparing different glucose polymers: maltodextrin (rapidly digestible) versus medium-chain pullulan (slowly but completely digestible) versus long-chain pullulan (indigestible). SUBJECTS/METHODS: In a randomized double-blind balanced crossover design, 35 subjects received drinks with 15 g test carbohydrate polymers. Key outcome measures were appetite scores, digestibility (in vitro test and breath hydrogen), and (in a subset) glucose and insulin levels. RESULTS: Digestibility, glucose and insulin data confirmed the rapid, slow and nondigestible nature of the test carbohydrates. Despite its low digestibility, only long-chain pullulan reduced appetite compared with the maltodextrin control, whereas the medium-chain pullulan did not. CONCLUSIONS: We conclude that glycemic responses per se have minimal effects on appetite, when tested in products differing in only carbohydrate digestibility rate and extent.


Subject(s)
Appetite , Blood Glucose/analysis , Dietary Carbohydrates/administration & dosage , Dietary Carbohydrates/metabolism , Insulin/blood , Adult , Analysis of Variance , Area Under Curve , Cross-Over Studies , Diet , Digestion , Double-Blind Method , Female , Glucans/metabolism , Glycemic Index , Humans , Linear Models , Male , Middle Aged , Polysaccharides/metabolism , Postprandial Period , Regression Analysis , Surveys and Questionnaires , Young Adult
5.
Eur J Clin Nutr ; 65(1): 81-6, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20859298

ABSTRACT

BACKGROUND/OBJECTIVES: To investigate the feasibility of Fabuless (previously called Olibra and Reducal) as a food ingredient for food intake and appetite reduction, by assessing the effects of food processing on efficacy. SUBJECTS/METHODS: In total, 24 healthy volunteers (16 female, 8 male; age: 18-43 years; body mass index: 18-37 kg/m(2)) took part in a randomized, placebo-controlled, double-blinded, cross-over trial. Yoghurt-based meal replacement drinks (containing processed or unprocessed Fabuless, or a control fat) were followed by an ad libitum lunch and evening meal (dinner). Key outcome measures were energy intake and self-reported appetite ratings. RESULTS: Compared with control, only unprocessed Fabuless reduced subsequent energy intake, although only during dinner (P < 0.01; control, processed and unprocessed: 4.3, 3.9 and 4.2 MJ, respectively) and not during lunch (3.6, 3.7 and 3.6 MJ). Self-reported appetite scores did not differ between treatments. CONCLUSIONS: Although modest effects of unprocessed Fabuless were seen on food intake, but not on appetite, the ingredient was not robust to common food-manufacturing processes (thermal and shear processing). Claims on reduced food intake and appetite relating to this ingredient in food products are, therefore, only valid if functionality has been demonstrated after all relevant processing and storage steps.


Subject(s)
Appetite Depressants/pharmacology , Appetite Regulation , Eating , Energy Intake , Adolescent , Adult , Body Mass Index , Cross-Over Studies , Double-Blind Method , Female , Food , Food Handling , Humans , Male , Satiety Response , Self Report , Yogurt , Young Adult
6.
Int J Obes (Lond) ; 35(2): 244-50, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20644555

ABSTRACT

BACKGROUND: Protease inhibitor 2 derived from potato (PI2) is claimed to reduce appetite and food intake, stimulate the satiety hormone cholecystokinin (CCK) and lower postprandial glucose peaks when taken before a meal. However, current literature is inconclusive with regard to its efficacy and mechanism. Furthermore, the potential effect of PI2 on appetite motivational ratings without an immediately following meal has not previously been reported. OBJECTIVE: To comprehensively test the effects of 30 mg PI2 in a minidrink on appetite ratings, subsequent food intake, and plasma CCK and glucose responses. DESIGN: Minidrinks with or without 30 mg PI2 were compared in three separate substudies (A, B and C), each using a two-way, placebo-controlled, balanced-order, cross-over design and 23 or 24 subjects (mean over groups: body mass index 25.0 kg m(-2), range 22.5-30.7 kg m(-2); age 41.3, range 18-62 years). The minidrink was given (A) 120 or (B) 30 min before an ad libitum lunch or (C) 30 min before a fixed lunch. Study parameters were self-reported satiety (substudies A and C), ad libitum meal intake (substudies A and B), and (in an n=12 subset) plasma CCK and blood glucose in all substudies. All results were analyzed using analysis of covariance. Protease-inhibitory activity of the PI2-containing minidrinks was assessed under simulated gut conditions. RESULTS: PI2 did not differ from control for any study parameters, in any substudy, despite confirmation of the inhibitory activity of PI2. CONCLUSIONS: In this study protease inhibition using PI2 in a minidrink at a dose of 30 mg, as commercially used, had no (functional) efficacy on a range of behavioral and physiological appetite and intake control measures.


Subject(s)
Appetite Regulation/drug effects , Cholecystokinin/blood , Eating/drug effects , Plant Preparations/pharmacology , Protease Inhibitors/pharmacology , Satiation/drug effects , Solanum tuberosum/chemistry , Adolescent , Adult , Appetite Regulation/physiology , Beverages , Cross-Over Studies , Eating/physiology , Female , Humans , Male , Middle Aged , Phytotherapy , Plant Preparations/administration & dosage , Postprandial Period , Protease Inhibitors/administration & dosage , Satiation/physiology , United Kingdom , Young Adult
7.
Obes Rev ; 11(3): 234-50, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20433660

ABSTRACT

The aim of this paper is to describe and discuss relevant aspects of the assessment of physiological functions - and related biomarkers - implicated in the regulation of appetite in humans. A short introduction provides the background and the present state of biomarker research as related to satiety and appetite. The main focus of the paper is on the gastrointestinal tract and its functions and biomarkers related to appetite for which sufficient data are available in human studies. The first section describes how gastric emptying, stomach distension and gut motility influence appetite; the second part describes how selected gastrointestinal peptides are involved in the control of satiety and appetite (ghrelin, cholecystokinin, glucagon-like peptide, peptide tyrosin-tyrosin) and can be used as potential biomarkers. For both sections, methodological aspects (adequacy, accuracy and limitation of the methods) are described. The last section focuses on new developments in techniques and methods for the assessment of physiological targets involved in appetite regulation (including brain imaging, interesting new experimental approaches, targets and markers). The conclusion estimates the relevance of selected biomarkers as representative markers of appetite regulation, in view of the current state of the art.


Subject(s)
Appetite Regulation/physiology , Energy Metabolism/physiology , Gastrointestinal Hormones/physiology , Gastrointestinal Tract/physiology , Peptide Hormones/metabolism , Biomarkers , Gastrointestinal Hormones/metabolism , Humans
8.
Neth J Med ; 67(2): 54-61, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19299847

ABSTRACT

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is characterised by high variability in clinical course and outcome. Accurate prediction of prognosis is needed to optimise treatment. Urinary alpha1-microglobulin and beta2-microglobulin are markers of tubulointerstitial injury and predict the risk of end-stage renal disease (ESRD) in idiopathic membranous nephropathy. We questioned the relevance of these markers in IgAN. METHODS: We included patients with biopsy proven IgAN, who were evaluated for proteinuria in our centre between 1995 and 2007. Data were analysed using univariate and multivariate Cox regression for the outcome variables ESRD and progression (rise in serum creatinine of >50% or start of immunosuppressive therapy). RESULTS: Seventy patients (71% men) were selected. Median age was 39 years, median serum creatinine 140 micromol/l, and median proteinuria 2.4 g/day. Median urinary alpha1-microglobulin excretion was 23.5 microg/min (range 3.5-275.3) and median urinary beta2-microglobulin excretion was 0.4 microg/min (range 0.1-62.1). Both alpha1m and beta2m correlated significantly with serum creatinine (r = 0.65, p<0.01 and r = 0.62, p<0.01) and total proteinuria (r = 0.35, p<0.01 and r = 0.28, p<0.05). During follow-up (median 75 months) 25 patients (36%) developed ESRD , and 46 patients (66%) showed progression. 19 patients (27%) were treated with immunosuppressive agents. In univariate analysis urinary alpha1- and beta2-microglobulin predicted ESRD and progression. In multivariate analysis only serum creatinine and urinary protein were independent predictors of both outcomes. CONCLUSION: Urinary excretion of low molecular weight proteins did not offer an advantage over total proteinuria and serum creatinine in predicting prognosis in patients with IgAN.


Subject(s)
Alpha-Globulins/urine , Creatine/blood , Glomerulonephritis, IGA/urine , Proteinuria/diagnosis , beta 2-Microglobulin/urine , Adolescent , Adult , Aged , Biomarkers , Disease Progression , Female , Glomerulonephritis, IGA/physiopathology , Humans , Male , Middle Aged , Molecular Weight , Multivariate Analysis , Prognosis , Prospective Studies , Young Adult
9.
Neth J Med ; 66(10): 408-15, 2008 Nov.
Article in English | MEDLINE | ID: mdl-19011266

ABSTRACT

Minimal change nephropathy (MCNS) and focal segmental glomerulosclerosis (FSGS) are the main causes of the idiopathic nephrotic syndrome. MCNS usually responds to steroids and the long-term prognosis is generally good. However, some patients require prolonged treatment with immunosuppressive agents. FSGS generally follows a less favourable course: patients do not always respond to steroids and may progress to end-stage renal disease. Recurrence of FSGS after renal transplantation is frequently observed and may result in graft loss. Recently, anecdotal case reports have described long-term resolution of nephrotic syndrome due to MCNS or FSGS after treatment with rituximab. We present four patients with nephrotic syndrome due to MCNS, FSGS or recurrence of FS GS after kidney transplantation, who were treated with rituximab with variable success. A review of the recent literature suggests that anti-CD20 antibodies may be a promising therapy, especially for patients with MCNS or idiopathic FSGS. Controlled studies are required to determine the efficacy of rituximab and to define which patients will benefit.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Glomerulosclerosis, Focal Segmental/drug therapy , Nephrosis, Lipoid/drug therapy , Nephrotic Syndrome/drug therapy , Adolescent , Antibodies, Monoclonal, Murine-Derived , Child , Female , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Male , Recurrence , Rituximab , Young Adult
10.
Int J Obes (Lond) ; 32(11): 1633-9, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18794896

ABSTRACT

OBJECTIVE: The ileal brake is a feedback mechanism activated by nutrients, especially fat, with marked effects on satiety. The effects of low doses of ileal fat on satiety are largely unknown. We therefore studied the effect of ileal vs oral delivery of low doses of fat on satiety and gut peptide secretion. DESIGN: Randomized, single-blind crossover design. SUBJECTS: Sixteen healthy, normal-weight volunteers (6 male; mean age 26 years, mean body mass index 22.4). INTERVENTION: Participants were intubated with a 290-cm-long nasoileal tube and consumed, on 3 consecutive days, either a liquid breakfast with 3 g fat followed by an ileal placebo infusion at t=105-150 min (treatment C) or a fat-free liquid breakfast followed by an ileal infusion of either an emulsion of 3 g (treatment 13 g) or 9 g (treatment 19 g) fat (safflower oil). MEASUREMENTS: Satiety parameters by visual analog scales and plasma concentrations of CCK and PYY. RESULTS: C significantly increased satiety and CCK secretion compared with the fat-free breakfast. Ileal fat perfusion of both 3 and 9 g 13 g and 19 g) significantly increased satiety during and after fat perfusion, without differences in satiety between 13 g and 19 g. During ileal fat infusion, CCK increased dose dependently, whereas PYY concentrations increased significantly only after 9 g of fat. Secretion of CCK but not of PYY correlated to satiety levels. CONCLUSION: Postprandial satiety following a liquid breakfast can be effectively and significantly increased by small amounts (as little as 3 g) of fat perfused into the ileum. Ileal fat dose-dependently increased CCK but not PYY secretion. The satiating effect of ileal fat may be partly mediated by CCK.


Subject(s)
Appetite/physiology , Cholecystokinin/blood , Dietary Fats/administration & dosage , Ileum/metabolism , Peptide YY/blood , Satiation/physiology , Adult , Cross-Over Studies , Female , Humans , Intubation, Gastrointestinal , Male , Middle Aged , Peptide YY/metabolism , Perfusion , Postprandial Period , Safflower Oil/administration & dosage , Single-Blind Method , Young Adult
12.
Physiol Behav ; 95(3): 271-81, 2008 Oct 20.
Article in English | MEDLINE | ID: mdl-18692080

ABSTRACT

With the rising prevalence of obesity and related health problems increases, there is increased interest in the gastrointestinal system as a possible target for pharmacological or food-based approaches to weight management. Recent studies have shown that under normal physiological situations undigested nutrients can reach the ileum, and induce activation of the so-called "ileal brake", a combination of effects influencing digestive process and ingestive behaviour. The relevance of the ileal brake as a potential target for weight management is based on several findings: First, activation of the ileal brake has been shown to reduce food intake and increase satiety levels. Second, surgical procedures that increase exposure of the ileum to nutrients produce weight loss and improved glycaemic control. Third, the appetite-reducing effect of chronic ileal brake activation appears to be maintained over time. Together, this evidence suggests that activation of the ileal brake is an excellent long-term target to achieve sustainable reductions in food intake. This review addresses the role of the ileal brake in gut function, and considers the possible involvement of several peptide hormone mediators. Attention is given to the ability of macronutrients to activate the ileal brake, and particularly variation attributable to the physicochemical properties of fats. The emphasis is on implications of ileal brake stimulation on food intake and satiety, accompanied by evidence of effects on glycaemic control and weight loss.


Subject(s)
Appetite Regulation/physiology , Digestive System Physiological Phenomena , Eating/physiology , Eating/psychology , Animals , Appetite Regulation/drug effects , Carbohydrates , Dietary Fats , Eating/drug effects , Gastrointestinal Hormones/metabolism , Humans , Proteins
13.
Neth J Med ; 65(9): 325-32, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17954951

ABSTRACT

Vasopressin is a critical regulator of water homeostasis. There are two major receptors for vasopressin: V1 and V2 receptors. Disturbances in water balance are commonly encountered in clinical practice and can be divided into disorders of urinary dilution and concentration. The major representatives of such disorders are diabetes insipidus and the syndrome of inappropriate secretion of antidiuretic hormone (SI ADH). Recent studies show that genetic forms of nephrogenic diabetes insipidus are due to mutations in the genes coding for the vasopressin V2 receptor (V2R) or aquaporin-2 (AQP2). Identification of the genes involved and analysis of the cellular fate of the V2R and AQP2 mutants are relevant for understanding the functioning of the V2R and AQP2 protein. These developments also have implications for future therapeutic options. The development of nonpeptide vasopressin receptor antagonists (VRAs) offers prospects for the treatment of euvolaemic (SI ADH) or hypervolaemic hyponatraemia (congestive heart failure or cirrhosis). Several nonpeptide VRAs are now in various stages of clinical trials. At present, only conivaptan is registered by the FD A for intravenous treatment of euvolaemic and hypervolaemic hyponatremia. A recent long-term study comparing tolvaptan with placebo in patients with chronic heart failure showed no reduction in risk of death and hospitalisation.


Subject(s)
Receptors, Vasopressin/therapeutic use , Vasopressins/physiology , Water-Electrolyte Balance/physiology , Water-Electrolyte Imbalance/physiopathology , Water/metabolism , Antidiuretic Hormone Receptor Antagonists , Diabetes Insipidus, Nephrogenic/drug therapy , Diabetes Insipidus, Nephrogenic/genetics , Diabetes Insipidus, Nephrogenic/physiopathology , Humans , Inappropriate ADH Syndrome/drug therapy , Inappropriate ADH Syndrome/genetics , Inappropriate ADH Syndrome/physiopathology , Mutation , Receptors, Vasopressin/genetics , Water-Electrolyte Imbalance/drug therapy , Water-Electrolyte Imbalance/genetics
14.
Aliment Pharmacol Ther ; 26 Suppl 2: 241-50, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18081667

ABSTRACT

BACKGROUND: The gastrointestinal tract elicits numerous signals regulating food intake and satiety, and recently many studies have been performed to elucidate the mechanisms regulating these signals. AIM: To describe the effects of the gastrointestinal tract on satiety, satiation and food intake. METHODS: A PubMed search was performed to identify and select the relevant literature using search terms including 'gastric satiety, intestine + satiety, satiation, cholecystokinin, ghrelin, peptide YY, glucagon-like peptide-1 and ileal brake'. RESULTS: Satiation, satiety and food intake result, among other factors, from signals originating in the stomach caused by distension and signals from the small intestine. These intestinal signals result from nutrient sensing in the gut and activate neural and humoral pathways. Activation of the distal part of the gut, the so called ileal brake, leads to reduction in hunger and food intake, and models of chronic ileal brake activation lead to massive weight loss. CONCLUSION: Gastrointestinal signals are crucial for the regulation of food intake, satiety and satiation. The ileal brake deserves special attention, as both ileal intubation studies and surgical studies demonstrate that activation of the ileal brake reduces food intake. In the surgical models, weight loss occurs without adaptation to the anorectic effects of ileal brake activation.


Subject(s)
Appetite Regulation/physiology , Eating/physiology , Gastrointestinal Tract/physiology , Neurosecretory Systems/physiology , Satiation/physiology , Animals , Humans
15.
Int J Radiat Oncol Biol Phys ; 51(5): 1346-53, 2001 Dec 01.
Article in English | MEDLINE | ID: mdl-11728696

ABSTRACT

PURPOSE: The predictive potential of tumor cell kinetic parameters may be improved when they are studied in relation to other microenvironmental parameters. The purpose of this investigation was to quantitatively categorize human tumor samples according to proliferation patterns. Second, it was examined whether these characteristics are retained after xenotransplantation. METHODS AND MATERIALS: Fifty tumor samples from head-and-neck cancer patients were immunohistochemically stained for Ki-67 and vessels. Also, parts of the samples were transplanted into nude mice. Tumors were categorized according to previously described patterns of proliferation. Vascular and proliferation patterns were analyzed using an image processing system. RESULTS: The 50 tumors were categorized into four patterns of proliferation by visual assessment: marginal (6), intermediate (10), random (21), and mixed (12). One tumor could not be classified. These patterns were quantified by calculating the Ki-67 labeling index in distinct zones at increasing distance from vessels yielding good discrimination and significant differences between patterns. The probability of growth after xenotransplantation was significantly higher for tumors with a labeling index and vascular density above the median value compared to tumors with both parameters below the median (82% vs. 35%). Fifty percent of the tumors retained their proliferation patterns after xenotransplantation. CONCLUSION: The categorization by proliferation pattern previously described by others was reproduced quantitatively and spatially related to the vascular network using a computerized image processing system. The combination of quantitative and architectural information of multiple microenvironmental parameters adds a new dimension to the study of treatment resistance mechanisms. Tumor models representative of the various patterns can be used to further investigate the relevance of these architectural patterns.


Subject(s)
Head and Neck Neoplasms/blood supply , Animals , Cell Division , Head and Neck Neoplasms/pathology , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Mice , Mice, Nude , Neoplasm Transplantation , Transplantation, Heterologous
16.
Int J Sports Med ; 22(4): 245-9, 2001 May.
Article in English | MEDLINE | ID: mdl-11414664

ABSTRACT

This study examines the reproducibility of gastro-intestinal blood flow measurements in the superior mesenteric artery (SMA) both before and immediately after exercise with Doppler ultrasound measurements. Twelve well-trained males (mean +/- SD: age 25.9 +/- 3.8 yr; VO2max 4.8 +/- 0.91 x min(-1)) were measured twice (trial 1 and 2) with a 1 week interval before and immediately after 1 hr cycling at 70% VO2max. Duplex scanning was performed with the athletes in supine position immediately after transition from a chair (before exercise) or bicycle (after exercise). The variability of three measurements before exercise was studied within both trials (short-term reproducibility) and the mean pre-exercise values were compared between the trials (long-term reproducibility). In addition, post-exercise measurements were compared in the same way. Reproducibility was tested using the coefficient of variation and Cronbach's alpha. Mean pre-exercise blood flow was 424 +/- 66 ml/min (n = 12) in trial 1 and 375 +/- 38 ml/min (n = 11) in trial 2. Immediately after exercise blood flow had decreased by 49% to 214 +/- 36 ml/min (p <0.01) in trial 1 and by 38% to 234 +/- 36 ml/min (p < 0.01) in trial 2. Blood flow before and after exercise was not significantly different between trials (paired t-test) and therefore reproducible at the group level. Before exercise a good to fair reproducibility was observed both at the short-term (Cronbach's alpha: 0.88 in trial 1, 0.73 in trial 2, n = 11), and at the long-term (alpha = 0.80, n= 11). In contrast, long-term reproducibility immediately after exercise was poor (alpha = -0.99, n = 8 and alpha = 0.36, n = 7 after the first and second cycling period, respectively). In conclusion, duplex scanning of SMA after a sitting-supine transition in well-trained subjects is not a reproducible method at the individual level for intestinal blood flow measurements immediately after exercise.


Subject(s)
Exercise/physiology , Mesenteric Artery, Superior/physiology , Adult , Data Collection , Exercise Test , Humans , Male , Mesenteric Artery, Superior/diagnostic imaging , Regional Blood Flow , Reproducibility of Results , Sports , Ultrasonography
17.
Gut ; 48(3): 435-9, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11171839

ABSTRACT

This review describes the current state of knowledge on the hazards of exercise and the potential benefits of physical activity on the gastrointestinal tract. In particular, acute strenuous exercise may provoke gastrointestinal symptoms such as heartburn or diarrhoea. A substantial part (20-50%) of endurance athletes are hampered by these symptoms which may deter them from participation in training and competitive events. Nevertheless, these acute symptoms are transient and do not hamper the athlete's health in the long term. The only exception is repeated gastrointestinal bleeding during training and competition, which in the long term may occasionally lead to iron deficiency and anaemia. In contrast, repetitive exercise periods at a relatively low intensity may have protective effects on the gastrointestinal tract. There is strong evidence that physical activity reduces the risk of colon cancer by up to 50%. Less convincing evidence exists for cholelithiasis and constipation. Physical activity may reduce the risk of diverticulosis, gastrointestinal haemorrhage, and inflammatory bowel disease although this cannot be substantiated firmly. Up to now, underlying mechanisms are poorly understood although decreased gastrointestinal blood flow, neuro-immuno-endocrine alterations, increased gastrointestinal motility, and mechanical bouncing during exercise are postulated. Future research on exercise associated digestive processes should give more insight into the relationship between physical activity and the function of the gastrointestinal tract.


Subject(s)
Digestive System Physiological Phenomena , Exercise/physiology , Gastrointestinal Diseases/physiopathology , Gastrointestinal Diseases/etiology , Gastrointestinal Transit/physiology , Humans , Regional Blood Flow
18.
J Cereb Blood Flow Metab ; 20(5): 861-70, 2000 May.
Article in English | MEDLINE | ID: mdl-10826537

ABSTRACT

Pathophysiologic parameters of the functional neovasculature and the blood-brain barrier of 9L-glioma in rat brain were measured noninvasively by dynamic 1H magnetic resonance imaging studies of gadolinium (Gd)-DTPA uptake. Changes of apparent [Gd-DTPA] uptake in time (CT[t]) were analyzed in a slice through the center of 10 9L-gliomas using fast T1 measurements. The distribution of the contrast agent was spatially correlated with the distribution of perfused microvessels as determined by immunohistochemical analysis. This method permits a distinction between perfused and nonperfused microvessels with a disrupted blood-brain barrier. In transverse slices of the whole tumor, a spatial correlation was observed between CT maps and the two-dimensional distribution of perfused microvessels. In the next step, Gd-DTPA uptake rates were spatially related to the perfused microvessel density (Np) or vascular surface area (Sp). In tumor voxels with perfused microvessels, a linear correlation was found between Gd-DTPA uptake rate constants (k values) and Np or Sp. No correlation was observed between k values and the total microvessel density. These are the first data that show a relation between Gd-DTPA uptake rates and parameters of the functional neovasculature in 9L-glioma growing in rat brain. Now that Gd-DTPA uptake studies can be related to parameters of the functional neovasculature, they may be used more efficiently as a prognostic tool before or during therapy.


Subject(s)
Brain Neoplasms/blood supply , Contrast Media , Gadolinium DTPA , Glioma/blood supply , Magnetic Resonance Imaging , Neovascularization, Pathologic/diagnosis , Animals , Brain Neoplasms/metabolism , Contrast Media/pharmacokinetics , Gadolinium DTPA/pharmacokinetics , Glioma/metabolism , Immunohistochemistry , Protons , Rats , Rats, Inbred F344
19.
Int J Sports Med ; 21(1): 65-70, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10683102

ABSTRACT

The effects of different modes of prolonged exercise and different drinks on gastroesophageal reflux and reflux-related symptoms were examined. In a cross-over design seven male triathletes performed two tests at one week intervals (50 min periods of alternately running, cycling and running at 70-75% VO2max), with supplementation of either a conventional sports drink (7% carbohydrates) or tap water. Gastroesophageal reflux (percentage time and number of periods esophageal pH < 4) was measured with an ambulant pH system before, during and after exercise. Percentage reflux time (+/- SEM) during running, cycling, running and recovery was 24.0 +/- 4.6, 8.2 +/- 4.8, 17.6 +/- 8.4 and 11.8 +/- 4.0 with carbohydrates and 7.4 +/- 2.9, 0 +/- 0, 2.4 +/- 1.4 and 0.2 +/- 0.2 with water, respectively. Reflux lasted longer during exercise as compared to the rest situation (5.6 + 1.4%), especially with carbohydrates, and lasted longer with carbohydrates than with water (P < 0.05; Wilcoxon signed rank test). In general, reflux lasted longer during running than during cycling (P < 0.05). Data on the number of reflux periods are concordant to these results. Chest pain was reported by one subject during running with carbohydrates. Heartburn during running was reported by two subjects with water and by one with carbohydrates. In conclusion, physical exercise increases gastroesophageal reflux, dependent on the mode of exercise and beverage used.


Subject(s)
Beverages , Bicycling/physiology , Dietary Carbohydrates , Gastroesophageal Reflux/etiology , Running/physiology , Adult , Chest Pain/etiology , Dietary Supplements , Gastric Emptying , Humans , Male
20.
Med Sci Sports Exerc ; 32(1): 134-42, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10647540

ABSTRACT

PURPOSE: Studies on the effect of exercise on gastrointestinal (GI) mucosal integrity have been limited to occult-blood tests, which were often nonspecific for human blood. The aim of our study was to investigate more aspects of this integrity. METHODS: We examined the effect of prolonged exercise and carbohydrate (CHO) supplementation on mucosal integrity in 22 male triathletes by measuring fecal lysozyme, alpha1-antitrypsin, and occult-blood loss, which was examined by two tests specific for human blood (Colon-Albumin and Monohaem test). Exercise consisted of two 150-min tests (alternately running, cycling, and running at 70-75% VO2max), either with a 7.0% CHO drink or water (W). Furthermore, GI symptoms during exercise were registered by questionnaire. RESULTS: Three subjects showed human albumin only in the first stool after exercise: twice with W and once with CHO. However, human hemoglobin (Hb) could not be detected in these samples. Four other subjects showed an elevated lysozyme concentration after exercise with CHO but not with W. Elevated alpha1-antitrypsin values were found in three of seven specimens in which either positive albumin tests and/or an elevated lysozyme concentration were demonstrated. Twenty-one subjects (95%) reported one or more GI symptoms during exercise. Incidence rates of different GI symptoms varied from 5 to 68%. Most symptoms were more frequent and lasted longer during running than during cycling but did not differ significantly between supplements and were not related to any mucosal integrity parameter. CONCLUSIONS: GI blood loss during exercise is of no clinical importance, at least in our study design with a group of well-trained male subjects who consumed a relatively high amount of fluid (up to 2.3 L). Nevertheless, an increased alpha1-antitrypsin and lysozyme concentration may indicate a transient local mucosal damage with an inflammatory response.


Subject(s)
Fluid Therapy , Gastric Mucosa/physiology , Intestinal Mucosa/physiology , Physical Exertion/physiology , Adult , Albumins/analysis , Bicycling/physiology , Chest Pain/etiology , Dietary Carbohydrates/administration & dosage , Eructation/etiology , Feces/chemistry , Feces/enzymology , Hemoglobins/analysis , Humans , Male , Muramidase/analysis , Occult Blood , Running/physiology , Surveys and Questionnaires , Water/administration & dosage , alpha 1-Antitrypsin/analysis
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