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1.
Curr Oncol Rep ; 25(9): 1057-1069, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37470973

ABSTRACT

PURPOSE OF REVIEW: The neuro-oncology team faces a unique challenge when assessing treatment response in patients diagnosed with glioblastoma. Magnetic resonance imaging (MRI) remains the standard imaging modality for measuring therapeutic response in both clinical practice and clinical trials. However, even for the neuroradiologist, MRI interpretations are not straightforward because of tumor heterogeneity, as evidenced by varying degrees of enhancement, infiltrating tumor patterns, cellular densities, and vasogenic edema. The situation is even more perplexing following therapy since treatment-related changes can mimic viable tumor. Additionally, antiangiogenic therapies can dramatically decrease contrast enhancement giving the false impression of decreasing tumor burden. Over the past few decades, several approaches have emerged to augment and improve visual interpretation of glioblastoma response to therapeutics. Herein, we summarize the state of the art for evaluating the response of glioblastoma to standard therapies and investigational agents as well as challenges and future directions for assessing treatment response in neuro-oncology. RECENT FINDINGS: Monitoring glioblastoma responses to standard therapy and novel agents has been fraught with many challenges and limitations over the past decade. Excitingly, new promising methods are emerging to help address these challenges. Recently, the Response Assessment in Neuro-Oncology (RANO) working group proposed an updated response criteria (RANO 2.0) for the evaluation of all grades of glial tumors regardless of IDH status or therapies being evaluated. In addition, advanced neuroimaging techniques, such as histogram analysis, parametric response maps, morphometric segmentation, radio pharmacodynamics approaches, and the integrating of amino acid radiotracers in the tumor evaluation algorithm may help resolve equivocal lesion interpretations without operative intervention. Moreover, the introduction of other techniques, such as liquid biopsy and artificial intelligence could complement conventional visual assessment of glioblastoma response to therapies. Neuro-oncology has evolved over the past decade and has achieved significant milestones, including the establishment of new standards of care, emerging therapeutic options, and novel clinical, translational, and basic research. More recently, the integration of histopathology with molecular features for tumor classification has marked an important paradigm shift in brain tumor diagnosis. In a similar manner, treatment response monitoring in neuro-oncology has made considerable progress. While most techniques are still in their inception, there is an emerging body of evidence for clinical application. Further research will be critically important for the development of impactful breakthroughs in this area of the field.

2.
J Neurooncol ; 159(3): 499-508, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35857249

ABSTRACT

BACKGROUND AND OBJECTIVE: Differentiating neoplastic and non-neoplastic brain lesions is essential to make management recommendations and convey prognosis, but the distinction between brain tumors and their mimics in practice may prove challenging. The aim of this study is to provide the incidence of brain tumor mimics in the neuro-oncology setting and describe this patient subset. METHODS: Retrospective study of adult patients referred to the Division of Neuro-oncology for a presumed diagnosis of brain tumor from January 1, 2005 through December 31, 2017, who later satisfied the diagnosis of a non-neoplastic entity based on neuroimaging, clinical course, and/or histopathology evaluation. We classified tumor mimic entities according to clinical, radiologic, and laboratory characteristics that correlated with the diagnosis. RESULTS: The incidence of brain tumor mimics was 3.4% (132/3897). The etiologies of the non-neoplastic entities were vascular (35%), inflammatory non-demyelinating (26%), demyelinating (15%), cysts (10%), infectious (9%), and miscellaneous (5%). In our study, 38% of patients underwent biopsy to determine diagnosis, but in 26%, the biopsy was inconclusive. DISCUSSION: Brain tumor mimics represent a small but important subset of the neuro-oncology referrals. Vascular, inflammatory, and demyelinating etiologies represent two-thirds of cases. Recognizing the clinical, radiologic and laboratory characteristics of such entities may improve resource utilization and prevent unnecessary as well as potentially harmful diagnostic and therapeutic interventions.


Subject(s)
Brain Neoplasms , Cysts , Adult , Biopsy , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/therapy , Humans , Retrospective Studies
3.
Psychol Med ; 40(7): 1193-201, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19903364

ABSTRACT

BACKGROUND: Affective symptoms are common in subjects with mild cognitive impairment (MCI), but there is disagreement whether these symptoms are predictive for Alzheimer's disease (AD). We investigated the predictive accuracy of affective symptoms for AD during a follow-up study in subjects with MCI, and whether the predictive accuracy was modified by age, the presence of amnestic MCI or the length of follow-up. METHOD: Newly referred subjects (n=263) with MCI older than 55 years were selected from a memory clinic and followed up after 2, 5 and 10 years. Predictors investigated were: symptoms of depression, anxiety, apathy and sleeping problems. RESULTS: Affective symptoms were present in 50-70% of the subjects. The average follow-up period was 5.4 years and 79 subjects (29%) developed AD. Sleeping problems were associated with a decreased risk for AD [odds ratio (OR) 0.35, p<0.001]. Symptoms of depression (OR 0.61, p=0.059) and anxiety (OR 0.58, p=0.051) showed a trend in the same direction. The OR of apathy for AD was 0.67 (p=0.14). Depression was associated with a decreased risk for AD only in subjects without amnestic MCI, but not in subjects with amnestic MCI. Moreover, anxiety was related to the risk for AD differently between subjects diagnosed with AD at the 5-year follow-up (OR 0.23) and subjects diagnosed with AD at the 10-year follow-up (OR 1.7). CONCLUSIONS: Affective symptoms are associated with a decreased risk for AD. The risk may be dependent on MCI subtype or length of follow-up, but it does not depend on age.


Subject(s)
Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Depressive Disorder/epidemiology , Aged , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neuropsychological Tests , Predictive Value of Tests , Severity of Illness Index , Sleep Initiation and Maintenance Disorders/diagnosis , Sleep Initiation and Maintenance Disorders/epidemiology
4.
Am J Gastroenterol ; 104(2): 371-83, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19174787

ABSTRACT

OBJECTIVES: Disease course in inflammatory bowel disease (IBD) is variable and difficult to predict. To optimize prognosis, it is of interest to identify phenotypic characteristics at disease onset and other prognostic factors that predict disease course. The aim of this study was to evaluate such factors in a population-based IBD group. METHODS: IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. A follow-up questionnaire was developed and medical records were reviewed. Patients were classified according to phenotype at diagnosis and risk factors were registered. Disease severity, cumulative medication use, and "surgical" and "nonsurgical" recurrence rates were calculated as outcome parameters. RESULTS: In total, 476 Crohn's disease (CD), 630 ulcerative colitis (UC), and 81 indeterminate colitis (IC) patients were diagnosed. In CD (mean follow-up 7.6 years), 50% had undergone resective surgery. In UC (mean follow-up 7 years), colectomy rate was 8.3%. First year cumulative recurrence rates per 100 patient-years for CD, UC, and IC were 53, 44, and 42%, respectively. In CD, small bowel localization and stricturing disease were negative prognostic factors for surgery, as was young age. Overall recurrence rate was increased by young age and current smoking. In UC, extensive colitis increased surgical risk. In UC, older age at diagnosis initially increased recurrence risk but was subsequently protective. CONCLUSIONS: This population-based IBD study showed high recurrence rates in the first year. In CD, small bowel localization, stricturing disease, and young age were predictive for disease recurrence. In UC, extensive colitis and older age at diagnosis were negative prognostic predictors.


Subject(s)
Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/epidemiology , Crohn Disease/diagnosis , Crohn Disease/epidemiology , Phenotype , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Colitis, Ulcerative/therapy , Crohn Disease/therapy , Follow-Up Studies , Humans , Incidence , Middle Aged , Predictive Value of Tests , Prognosis , Recurrence , Risk Factors , Sex Factors , Young Adult
5.
Br J Cancer ; 99(1): 30-6, 2008 Jul 08.
Article in English | MEDLINE | ID: mdl-18577993

ABSTRACT

The short-term beneficial effects of physical rehabilitation programmes after cancer treatment have been described. However, little is known regarding the long-term effects. The purpose of this study was to investigate the long-term effects of high-intensity resistance training compared with traditional recovery. A total of 68 cancer survivors who completed an 18-week resistance training programme were followed for 1 year. During the 1-year follow-up, 19 patients dropped out (14 due to recurrence of cancer). The remaining 49 patients of the intervention group were compared with a group of 22 patients treated with chemotherapy in the same period but not participating in any rehabilitation programme. Outcome measures were muscle strength, cardiopulmonary function, fatigue, and health-related quality of life. One year after completion of the rehabilitation programme, the outcome measures in the intervention group were still at the same level as immediately after rehabilitation. Muscle strength at 1 year was significantly higher in patients who completed the resistance training programme than in the comparison group. High-intensity resistance training has persistent effects on muscle strength, cardiopulmonary function, quality of life, and fatigue. Rehabilitation programmes for patients treated with chemotherapy with a curative intention should include high-intensity resistance training in their programme.


Subject(s)
Neoplasms/rehabilitation , Weight Lifting , Adult , Exercise Therapy , Female , Follow-Up Studies , Health Status , Humans , Male , Middle Aged , Motor Skills , Quality of Life
6.
Eur Respir J ; 31(5): 934-42, 2008 May.
Article in English | MEDLINE | ID: mdl-18184682

ABSTRACT

Optimal collection and analysis of exhaled breath condensate (EBC) are prerequisites for standardisation and reproducibility of assessments. The present study aimed to assess reproducibility of EBC volume, hydrogen peroxide (H(2)O(2)), 8-isoprostane and cytokine measurements using different condensers, including a newly developed glass condenser. At four points in time, 30 healthy subjects performed sequential EBC collections randomly using the following four condensers: glass, silicone, EcoScreen (Erich Jaeger GmbH, Hoechberg, Germany) and an optimised glass condenser. In small EBC samples, H(2)O(2) was measured by spectrophotometer, 8-isoprostane by enzyme immunoassay, and cytokines by multiplexed xMAP technology (Luminex Corporation, Austin, TX, USA). The optimised glass condenser yielded significantly more EBC volume (median 2,025 microL, interquartile range 1,600-2,525). The reproducibility of EBC volume, yielded by the new glass condenser, was comparable with EcoScreen (19-20 coefficients of variation (CV)%), but was significantly better compared with silicone and glass (29-37 CV%). The new condenser was associated with significantly more detections of H(2)O(2), 8-isoprostane, interleukin-2, -4, -5 and -13, and tumour necrosis factor-alpha. Isoprostane concentrations were significantly higher using the new condenser, whereas H(2)O(2) and cytokine concentrations were not. Reproducibility of biomarkers was equally variable for all condenser types. In conclusion, significantly more exhaled breath condensate volume and biomarker detections were found using the optimised glass condenser, including higher 8-isoprostane levels. However, biomarker reproducibility in exhaled breath condensate in healthy adults was not influenced by the type of condenser.


Subject(s)
Breath Tests/instrumentation , Specimen Handling/instrumentation , Adult , Biomarkers , Breath Tests/methods , Dinoprost/analogs & derivatives , Dinoprost/analysis , Exhalation , Female , Humans , Hydrogen Peroxide/analysis , Interleukins/analysis , Male , Reproducibility of Results , Sensitivity and Specificity , Specimen Handling/methods , Tumor Necrosis Factor-alpha/analysis
7.
Int J Med Inform ; 77(3): 199-207, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17631412

ABSTRACT

OBJECTIVE: To evaluate the feasibility and acceptability of a computer reminder system (CRS) to improve prescribing behaviour in general practice and to explore the strengths and weaknesses of a reminder system. One group of GPs received reminders on cholesterol lowering drugs, the other group on antibiotics, asthma and COPD drugs. METHODS: Process evaluation of the computer reminder system being used by 53 GPs in 20 practices, by means of an analysis of the research database of the CRS. In addition, a questionnaire and semi-structured face-to-face interview were conducted with all GP practices, two project leaders, and one technical consultant. RESULTS: The strategy was largely carried out as planned, although the development period for the CRS had to be extended. Nine percent of the GPs dropped out. We found a significant learning curve without extinguishing effect (p=0.03) for the antibiotics reminders. The questionnaire showed that, in general, GPs were satisfied with the user-friendliness and the content of the different types of reminders, but less satisfied with certain specific technical performance issues of the system. The GPs reported mixed feelings towards the CRS in the interviews. They were generally positive about the guidelines themselves, but negative regarding to the organisational context and the method of implementing the CRS. GPs stated that they sometimes manipulated the system to bypass reminders. Interviews with the project leaders and technical consultant revealed barriers to cooperation and miscommunication between the different parties, and technical problems with multiple updates of the GP information system and the operating system. CONCLUSIONS: This process evaluation demonstrated that the implementation of the CRS was mainly carried out as planned, but the subjective experience of working with the CRS was not only positive. Participating GPs had mixed feelings, and quite a number of barriers need to be addressed to facilitate large-scale implementation of the CRS. Costs cannot be neglected, so it is important to analyse the balance between costs and effects.


Subject(s)
Attitude of Health Personnel , Drug Prescriptions , Practice Patterns, Physicians'/standards , Primary Health Care , Reminder Systems , Anti-Bacterial Agents/therapeutic use , Anticholesteremic Agents/therapeutic use , Asthma/drug therapy , Feasibility Studies , Humans , Interviews as Topic , Netherlands , Pulmonary Disease, Chronic Obstructive/drug therapy , Surveys and Questionnaires
8.
Neurol Clin ; 36(3): 449-466, 2018 08.
Article in English | MEDLINE | ID: mdl-30072065

ABSTRACT

Patients with brain tumor encounter a wide spectrum of tumor and treatment-related complications during their disease course. Tumors may serve as seizure substrates, are associated with a hypercoagulable state that results in thromboembolic complications, and may influence mood and cognition. Antitumor and supportive therapies may also have deleterious effects. Herein, we discuss major aspects of supportive care for patients with brain tumors, with attention to benefit and complications derived from the management of seizures, brain edema, venous thromboembolism, fatigue, mood alterations, and cognitive dysfunction.


Subject(s)
Brain Neoplasms/complications , Brain Edema/etiology , Brain Edema/therapy , Cognition Disorders/etiology , Cognition Disorders/therapy , Humans , Seizures/etiology , Seizures/therapy , Venous Thromboembolism/etiology , Venous Thromboembolism/therapy
9.
CNS Oncol ; 6(4): 275-280, 2017 10.
Article in English | MEDLINE | ID: mdl-29034739

ABSTRACT

Intramedullary spinal cord metastasis is an increasingly common diagnosis in patients with cancer largely owing to new imaging techniques and the increase lifespan of patients with malignant tumors. The diagnosis confers significant morbidity and a poor prognosis. Mainstay palliative treatment options include corticosteroids, fractionated radiotherapy and surgery in select cases. In the modern era of immunotherapy for the treatment of several tumor types, the efficacy of these agents against parenchymal CNS tumors remains unanswered. Here, we report a case of regression of an intramedullary spinal cord metastasis with a checkpoint inhibitor.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Spinal Cord Neoplasms/drug therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Adenocarcinoma of Lung , Aged , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Nivolumab , Spinal Cord Neoplasms/secondary
10.
Brain Res ; 1120(1): 1-12, 2006 Nov 20.
Article in English | MEDLINE | ID: mdl-17020749

ABSTRACT

Glial cell line-derived neurotrophic factor (GDNF) has shown robust neuroprotective and neuroreparative activities in various animal models of Parkinson's Disease or amyotrophic lateral sclerosis (ALS). The successful use of GDNF as a therapeutic in humans, however, appears to have been hindered by its poor bioavailability to target neurons in the central nervous system (CNS). To improve delivery of exogenous GDNF protein to CNS motor neurons, we employed chemical conjugation techniques to link recombinant human GDNF to the neuronal binding fragment of tetanus toxin (tetanus toxin fragment C, or TTC). The predominant species present in the purified conjugate sample, GDNF:TTC, had a molecular weight of approximately 80 kDa as determined by non-reducing SDS-PAGE. Like GDNF, addition of GDNF:TTC to culture media of neuroblastoma cells expressing GFRalpha-1/c-RET produced a dose-dependent increase in cellular phospho-c-RET levels. Treatment of cultured midbrain dopaminergic neurons with either GDNF or the conjugate similarly promoted both DA neuron survival and neurite outgrowth. However, in contrast to mice treated with GDNF by intramuscular injection, mice receiving GDNF:TTC revealed intense GDNF immunostaining associated with spinal cord motor neurons in fixed tissue sections. That GDNF:TTC provided neuroprotection of axotomized motor neurons in neonatal rats further revealed that the conjugate retained its GDNF activity in vivo. These results indicate that TTC can serve as a non-viral vehicle to substantially improve the delivery of functionally active growth factors to motor neurons in the mammalian CNS.


Subject(s)
Glial Cell Line-Derived Neurotrophic Factor/pharmacology , Motor Neurons/drug effects , Neuroprotective Agents/pharmacology , Peptide Fragments/pharmacology , Spinal Cord/cytology , Tetanus Toxin/pharmacology , Analysis of Variance , Animals , Animals, Newborn , Axotomy/methods , Cell Survival/drug effects , Cells, Cultured , Dopamine/metabolism , Dose-Response Relationship, Drug , Glial Cell Line-Derived Neurotrophic Factor/chemistry , Humans , Immunohistochemistry/methods , Male , Mesencephalon/cytology , Mice , Mice, Inbred C57BL , Neuroblastoma , Peptide Fragments/chemistry , Protein Transport/drug effects , Rats , Rats, Sprague-Dawley , Recombinant Proteins/pharmacology , Tetanus Toxin/chemistry , Tyrosine 3-Monooxygenase/metabolism
11.
Int Health ; 8(5): 354-9, 2016 09.
Article in English | MEDLINE | ID: mdl-27118483

ABSTRACT

BACKGROUND: Prevalence of metabolic syndrome (MetS) and consequential cardiovascular disease (CVD) events are on the increase in Nigeria. The study aimed to identify the prevalence of 10-year CVD risk in a Nigerian population and assess its relationship with different indices of MetS. METHOD: A cross-sectional study was carried out on apparently healthy persons aged 18 years of age or older. Ten-year risk was calculated using the ATPIII/Framingham criteria. Subjects with risk score <10% were considered as having low risk, 10-20% moderate risk and >20% at high risk of developing CVD in 10 years. MetS was defined based on the Joint Scientific Statement on Harmonizing the MetS. RESULT: Of the 211 subjects, mean age was 51.3±17.3 years. Average risk of developing CVD in the next 10 years was 3.7±5.3%. Prevalence of low, moderate and high risk of developing CVD among study participants was 86.3% (95% CI 82.0-91.3%), 11.8% (95% CI 6.9-16.1%) and 1.9% (95% CI 0.0-3.8%), respectively. Prevalence of MetS was 26.7% (95% CI 21.0-33.3%). There was poor agreement between MetS and the CVD risk scores (kappa=0.209, p=0.001) CONCLUSIONS: The results showed that complementary use of MetS and CVD risk score is imperative, as there is indication of risk in individuals without MetS. Also a large proportion of the study population requires lifestyle intervention. These findings provide the evidence necessary to tailor public health interventions in this population, especially towards younger age groups.


Subject(s)
Cardiovascular Diseases/etiology , Metabolic Syndrome/complications , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Metabolic Syndrome/epidemiology , Middle Aged , Nigeria/epidemiology , Prevalence , Proportional Hazards Models , Risk Assessment , Risk Factors , Time Factors
12.
Diabetes Metab Syndr ; 10(1): 13-8, 2016.
Article in English | MEDLINE | ID: mdl-26327395

ABSTRACT

AIMS: Physical activity is an essential determinant of health. However, there is dearth of evidence regarding prevalence of physical activity in developing countries, especially its association with metabolic syndrome risk factors. This study assessed the association of physical activity with metabolic syndrome in a Nigerian population. MATERIALS AND METHODS: A cross-sectional study was carried out on apparently healthy persons who are ≥ 18 years old. The World Health Organisation (WHO) Global Physical Activity Questionnaire (GPAQ) was used to collect five domains of physical activity. Participants were classified as physically active or inactive based on meeting the cut-off value of 600 MET-min/week. Metabolic syndrome was diagnosed using the Joint Scientific Statement on Harmonizing the Metabolic Syndrome criteria. RESULTS: Overall prevalence of physically active individuals was 50.1% (CI: 45.6-54.7%). Physical inactivity is significantly more in females (p<0.01) and among participants >40 years old (p<0.0001). Whereas individuals with metabolic syndrome appeared more likely to be physically active (OR=1.48, CI: 0.71-3.09); physical inactivity showed to exist more among participants who were living in urban area (OR=6.61, CI: 3.40-12.85, p<0.001). Participants with prediabetes (OR=1.69, CI: 0.62-4.61) and diabetes (OR=1.91, CI: 0.65-5.63) were more likely to be physically inactive as compared to other metabolic syndrome risk factors. CONCLUSION: The high prevalence of physical inactivity in this study population is a clear indication that concerted efforts to improve physical activity may be required. However, it seems that metabolic syndrome is not improved by being physically active. This suggests that interventions directed at physical activity alone may not produce optimal efficacy in this study population.


Subject(s)
Exercise , Metabolic Syndrome/epidemiology , Adult , Cross-Sectional Studies , Developing Countries , Female , Humans , Male , Middle Aged , Nigeria , Risk Factors , World Health Organization
13.
Diabetes Metab Syndr ; 10(3): 121-7, 2016.
Article in English | MEDLINE | ID: mdl-26907969

ABSTRACT

BACKGROUND: In sub-Saharan Africa, there is no precise use of metabolic syndrome (MetS) definitions and risk factors screening indices in many clinical and public health services. Methods proposed and used in Western populations are adopted without validation within the local settings. The aim of the study is to assess obesity indices and cut-off values that maximise screening of MetS and risk factors in the Nigerian population. METHOD: A consolidated analysis of 2809 samples from four population-based cross-sectional study of apparently healthy persons≥18 years was carried out. Optimal waist circumference (WC) and waist-to-height ratio (WHtR) cut points for diagnosing MetS and risk factors were determined using Optimal Data Analysis (ODA) model. The stability of the predictions of the models was also assessed. RESULTS: Overall mean values of BMI, WC and WHtR were 24.8±6.0kgm(-2), 84.0±11.3cm and 0.52±0.1 respectively. Optimal WC cut-off for discriminating MetS and diabetes was 83cm in females and 85cm in males, and 82cm in females and 89cm in males, respectively. WC was stable in discriminating diabetes than did WHtR and BMI, while WHtR showed better stability in predicting MetS than WC and BMI. CONCLUSION: The study shows that the optimal WC that maximises classification accuracy of MetS differs from that currently used for sub-Saharan ethnicity. The proposed global WHtR of 0.50 may misclassify MetS, diabetes and hypertension. Finally, the WC is a better predictor of diabetes, while WHtR is a better predictor of MetS in this sample population.


Subject(s)
Metabolic Syndrome/diagnosis , Obesity/diagnosis , Adult , Body Height , Cross-Sectional Studies , Diabetes Mellitus/diagnosis , Female , Humans , Male , Metabolic Syndrome/epidemiology , Middle Aged , Nigeria/epidemiology , Obesity/epidemiology , Predictive Value of Tests , Risk Factors , Sensitivity and Specificity , Waist Circumference
14.
Cardiovasc Res ; 19(4): 201-5, 1985 Apr.
Article in English | MEDLINE | ID: mdl-4005896

ABSTRACT

We studied in 20 splenectomised dogs the incidence of early intravascular hepatic pooling after administration of E. coli endotoxin. Autologous red cells were labelled in vitro with 99mTc. Bloodpool imaging and haemodynamic measurements were performed simultaneously. Changes in hepatic red cell volume were estimated from alterations in hepatic activity. In 10 dogs, hepatic red cell activity increased considerably (156 to 359% of the basal value). In the remaining animals the hepatic activity did not change markedly or even decreased. The decline in arterial pressure and cardiac output seemed more pronounced in dogs with clear evidence of hepatic pooling. However no significant differences in absolute haemodynamic values could be demonstrated between dogs with and without pooling. It is concluded that an hepatic outflow block is not a constant feature of canine endotoxin shock. Absolute haemodynamic values do not depend on the presence of an outflow block. Thus the presence of hepatic pooling need not make the canine model inappropriate for studies on human sepsis.


Subject(s)
Erythrocyte Volume , Erythrocytes/physiology , Liver/blood supply , Shock, Septic/physiopathology , Animals , Blood Pressure , Cardiac Output , Disease Models, Animal , Dogs , Endotoxins/pharmacology , Female , Heart/diagnostic imaging , Liver/diagnostic imaging , Male , Radionuclide Imaging , Splenectomy
15.
Cardiovasc Res ; 19(5): 278-87, 1985 May.
Article in English | MEDLINE | ID: mdl-3995523

ABSTRACT

Conflicting data exist in literature about the effects of endotoxin on skeletal muscle perfusion and metabolism during canine endotoxin shock. In 12 dogs we therefore studied (six control and six endotoxin treated, 1.5 mg X kg-1) under etomidate (4 mg X kg-1 X h-1) anaesthesia muscle blood flow (radioactive microspheres) in fore limb, thorax, diaphragm and hind limb (five different muscles) and skin blood flow before (t = 0) and 90 and 120 min after endotoxin. We also measured blood flow in the femoral artery and vein (electromagnetic flow transducers) and the arteriovenous differences of oxygen, lactate, glucose and FFA over the femoral vascular bed (at t = 0, 30, 90 and 120 min). Endotoxin administration caused a fall of flow in the femoral artery and vein (by 65 and 63%, respectively at t = 15). After t = 60 flow in the femoral artery and vein increased slowly but the flows were still below the preshock values at t = 20 (by 33 and 50%, respectively). Skeletal muscle and skin flow did not decrease or even increased after endotoxin but decreased in the control group. Percentage of cardiac output distributed to brachial, intercostal and hind limb muscle and skin increased after endotoxin (by 163, 167, 111 and 120%, respectively at t = 20). The five muscles of the hind limb did not respond differently to endotoxin. In spite of diminished arterial inflow, skeletal muscle perfusion was thus maintained in the hind limb, probably due to closing of shunts and redistribution of blood away from bone. Oxygen extraction but also lactate release by the femoral bed had increased during endotoxin shock. After endotoxin femoral glucose extraction was only elevated at t = 30 when arterial glucose concentration had also increased. The femoral bed produced free fatty acids (FFA) but during endotoxin shock the arteriovenous concentration difference of FFA decreased. Our data suggest that skeletal muscle flow nor oxygen consumption and glucose metabolism is affected during 2 h of canine endotoxin shock. Lactate production, however, tended to increase.


Subject(s)
Muscles/blood supply , Shock, Septic/physiopathology , Animals , Blood Glucose/metabolism , Cardiac Output , Dogs , Fatty Acids, Nonesterified/blood , Femoral Artery , Femoral Vein , Hemodynamics , Hindlimb/physiopathology , Lactates/blood , Lactic Acid , Muscles/metabolism , Regional Blood Flow , Shock, Septic/metabolism
16.
Am J Clin Nutr ; 61(1): 69-74, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7825541

ABSTRACT

The effect of the amount of protein intake (12% and 21% of total energy intake, diet A and diet B, respectively) on nitrogen balance and whole-body protein turnover (PT) was measured in 19 young men and 10 young women (aged 30 +/- 5 and 27 +/- 4 y, respectively). In young adults, mean nitrogen balance was approximately zero during diet A whereas it was positive during diet B. In young adults, PT was significantly higher during diet B in comparison with diet A. This was also seen in elderly subjects, as described before. From a comparison of the current data with the data previously obtained in elderly subjects it can be concluded that during diet A young adults had PT rates higher than those of elderly subjects. During diet B, PT of young men was comparable with the PT of elderly men whereas young women still had higher PT rates than elderly women (even when corrections were made for differences in body composition).


Subject(s)
Aging/metabolism , Dietary Proteins/administration & dosage , Proteins/metabolism , Adult , Aged , Cross-Over Studies , Female , Humans , Male , Nitrogen/metabolism , Protein Biosynthesis
17.
Am J Clin Nutr ; 73(4): 797-806, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11273856

ABSTRACT

BACKGROUND: Essential fatty acids (EFAs) in umbilical cord blood samples are associated with attained birth weight in premature infants and low-birth-weight neonates. OBJECTIVE: The objective was to investigate relations between the EFA composition of cord and maternal plasma phospholipids and birth weight in term neonates. DESIGN: This was a cross-sectional study in 627 singletons born at term. The plasma phospholipid EFA composition of the mothers was determined by gas-liquid chromatography at study entry (< or = 16 wk gestation), at delivery, and in cord plasma at birth. Birth weights were normalized to SD scores. RESULTS: In cord plasma, the dihomo-gamma-linolenic acid concentration was positively related to weight SD scores. Both arachidonic acid (AA) and docosahexaenoic acid (DHA) were negatively related to weight SD scores. EFA-status indicators showed similar negative associations, whereas eicosatrienoic acid concentrations were positively related to neonatal size. In maternal plasma, proportions of n-3 long-chain polyenes (LCPs) and n-6 LCPs decreased during pregnancy. Larger decreases in AA, DHA, n-3 LCP, and n-6 LCP fractions were observed in mothers of heavier babies. Higher concentrations of LCPs in maternal plasma were, however, not related to a larger infant size at birth. CONCLUSIONS: A lower biochemical EFA status in umbilical cord plasma and a larger decrease in maternal plasma LCP concentrations are associated with a higher weight-for-gestational-age at birth in term neonates. Our findings do not support a growth-stimulating effect of AA or DHA; however, they do suggest that maternal-to-fetal transfer of EFAs might be a limiting factor in determining neonatal EFA status.


Subject(s)
Birth Weight , Fatty Acids, Essential/blood , Fetal Blood/chemistry , Maternal-Fetal Exchange , Phospholipids/blood , 8,11,14-Eicosatrienoic Acid/blood , Arachidonic Acid/blood , Chromatography, Gas , Cross-Sectional Studies , Docosahexaenoic Acids/blood , Embryonic and Fetal Development , Female , Gestational Age , Humans , Infant, Newborn , Male , Nutritional Status , Phospholipids/chemistry , Polyenes/blood , Pregnancy
18.
Am J Clin Nutr ; 73(3): 549-53, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11237930

ABSTRACT

BACKGROUND: An easy and cheap method for validating reported energy intake (EI) is needed. OBJECTIVE: Reported EI was compared with calculated energy expenditure (EE(calc)) and with energy expenditure measured by the doubly labeled water method (EE(DLW)). DESIGN: EE was calculated on the basis of basal metabolic rate (BMR) measured with the ventilated-hood technique and physical activity (PA) measured with a triaxial accelerometer (EE(VH+PA)) and on the basis of BMR estimated by using World Health Organization equations and PA (EE(WHO+PA)): EE(calc) = -1.259 + 1.55 x BMR + 0.076 x counts/min (r(2) = 0.90, P = 0.0001). Subjects [n = 12 men and 12 women aged 60 +/- 3 y; body mass index (in kg/m(2)): 26 +/- 4] reported their food intakes for 7 d and EE(DLW), EE(VH+PA), and EE(WHO+PA) were assessed over the same 7 d. RESULTS: Reported EI (9.0 +/- 2.1 MJ/d) was lower (P: < 0.0001) than were EE(DLW) (11.3 +/- 2.3 MJ/d), EE(VH+PA) (10.8 +/- 1.7 MJ/d), and EE(WHO+PA) (10.8 +/- 1.8 MJ/d). Underreporting was 19.4 +/- 14.0%, 16.7 +/- 13.6%, and 16.4 +/- 15.5% on the basis of EE(DLW), EE(VH+PA), and EE(WHO+PA), respectively. The difference of 2.7 +/- 8.0% between EE(DLW) and EE(VH+PA) was not related to the average of both percentages and was not significantly different from zero. The percentage of underreporting calculated with EE(WHO+PA) was not significantly different from that calculated with EE(DLW). CONCLUSIONS: The use of a combination of BMR (measured or estimated) and PA is a good method for validating reported EI. There was no significant difference between the percentage of underreporting calculated with EE(VH+PA), EE(WHO+PA), or EE(DLW).


Subject(s)
Energy Intake/physiology , Energy Metabolism , Ergometry/methods , Motor Activity/physiology , Aged , Basal Metabolism , Deuterium Oxide , Eating , Female , Humans , Male , Middle Aged , Oxygen Isotopes , Reproducibility of Results , Self Disclosure , Water
19.
Am J Clin Nutr ; 51(3): 393-8, 1990 Mar.
Article in English | MEDLINE | ID: mdl-2309645

ABSTRACT

In Maastricht and Zeist, The Netherlands, and Tromsø, Norway, a well-controlled study was performed on the effect of a fish-enriched diet on serum lipids, apolipoproteins A-1 and B, and fatty acid compositions of serum triglycerides and cholesterol esters. For 6 wk healthy male volunteers were given a daily dietary supplement consisting of 135 g mackerel paste (experimental group, n = 42) or meat paste (control group, n = 42). Dietary adherence was calculated on the basis of urinary excretion of a standard amount of lithium added to the supplements. Average compliance was 80%. Low-density-lipoprotein (LDL) and total serum cholesterol concentrations were unaffected. High-density-lipoprotein (HDL) cholesterol increased to a comparable degree in both groups. Triglyceride content of serum decreased in the fish group. Apolipoproteins A-1 and B (both in Maastricht subjects only) were only slightly affected. In the mackerel group the n-3 fatty acids increased significantly in serum cholesterol esters and triglycerides; the n-6 fatty acids decreased in cholesterol esters only.


Subject(s)
Apolipoproteins/blood , Diet , Fishes , Lipids/blood , Adult , Animals , Cholesterol/blood , Cholesterol Esters/blood , Cholesterol, HDL/blood , Humans , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Male , Middle Aged , Triglycerides/blood
20.
Am J Clin Nutr ; 71(3): 752-6, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10702169

ABSTRACT

BACKGROUND: Obesity in Prader-Willi syndrome (PWS) seems to be related to a low basal metabolic rate (BMR). In addition, abnormal sleep patterns reported in PWS might affect sleeping metabolic rate (SMR). OBJECTIVE: Our objective was to assess BMR and SMR adjusted for fat-free mass in young PWS patients. DESIGN: Subjects were 17 PWS patients (10 females and 7 males aged 7.5-19.8 y) and 17 obese control subjects matched for sex and bone age. SMR was measured in a respiratory chamber, BMR with a ventilated-hood system, and body composition by deuterium dilution. RESULTS: BMR and SMR were significantly lower in the PWS group than in the control group (5.36 +/- 1.18 and 4.62 +/- 1.08 MJ/d compared with 6.38 +/- 1.55 and 5.60 +/- 1.52 MJ/d, respectively; P < 0.05). When fat-free mass was included in the analysis, multiple regression showed no differences in BMR and SMR between groups. When weight was included in the analysis instead of fat-free mass, SMR was lower in the PWS group. Fat-free mass was lower in the PWS group both as an absolute value and when adjusted for height. CONCLUSION: BMR and SMR are low in young patients with PWS because of a low fat-free mass.


Subject(s)
Basal Metabolism , Body Composition , Energy Metabolism , Prader-Willi Syndrome/metabolism , Rest/physiology , Sleep/physiology , Adolescent , Adult , Body Mass Index , Child , Female , Humans , Male , Regression Analysis
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