Metabolic Changes In Patients Research Articles

Computational modeling of cancer cachexia

Measurements of whole-body energy expenditure, body composition, and in-vivo metabolic fluxes are required to quantitatively understand involuntary weight loss in cancer cachexia. Such studies are rare because cancer cachexia occurs near the end of life when invasive metabolic tests may be precluded. Thus, models of cancer-associated weight loss are an important tool for helping to understand this debilitating condition. A computational model of human macronutrient metabolism was recently developed that simulates the normal metabolic adaptations to semi-starvation and re-feeding. Here, this model was used to integrate data on the metabolic changes in patients with cancer cachexia. The resulting computer simulations show how the known metabolic disturbances synergize with reduced energy intake to result in a progressive loss of body weight, fat mass, and fat-free mass. The model was also used to simulate the effects of nutritional support and investigate inhibition of lipolysis versus proteolysis as potential therapeutic approaches for cancer cachexia. Computational modeling is a new tool that can integrate clinical data on the metabolic changes in cancer cachexia and provide a conceptual framework to help understand involuntary weight loss and predict the effects of potential therapies.

Content-Specific Delusions From Right Caudate Lacunar Stroke: Association with Prefrontal Hypometabolism

Content-Specific Delusions From Right Caudate Lacunar Stroke: Association with Prefrontal Hypometabolism

Haemodynamic, electrolyte and metabolic changes during percutaneous nephrolithotomy

The objectives were to evaluate haemodynamic, electrolyte and metabolic changes in patients undergoing percutaneous nephrolithotomy when normal saline was used for irrigation; and to correlate these changes with irrigation time, volume of irrigation fluid absorbed and number of percutaneous interventions. Twenty adults undergoing percutaneous nephrolithotomy were studied. Heart rate, systolic and diastolic blood pressure, arterial blood gases, electrolytes and temperature were monitored before, during and after irrigation. Haemoglobin, urea and creatinine values were recorded before and 24 h after the procedure. Durations of anaesthesia and irrigation; volumes of irrigation fluid used and effluent fluid; and number of percutaneous interventions during the procedure were also recorded. No significant changes occurred in mean heart rate, systolic and diastolic blood pressure, electrolytes, haemoglobin, urea and creatinine. There was a significant fall in mean pH in postoperative period (P = 0.003) and bicarbonate values showed a negative correlation with duration of irrigation. Number of percutaneous interventions had positive correlations with duration of irrigation and volume of irrigant fluid absorbed. No significant changes occurred in haemodynamics and electrolytes, but there was a trend towards metabolic acidosis. Arterial blood gases should be monitored during and after PCNL in cases with prolonged irrigation time, repeated percutaneous interventions and patients having compromised renal function and metabolic status.

Acute metabolic brain changes following traumatic brain injury and their relevance to clinical severity and outcome

Background: Conventional MRI can provide critical information for care of patients with traumatic brain injury (TBI), but MRI abnormalities rarely correlate to clinical severity and outcome. Previous magnetic resonance spectroscopy...

Metabolic Therapy for Patients with Diabetes Mellitus and Coronary Artery Disease

Patients with diabetes mellitus and ischemic heart disease more frequently develop heart failure and have a greater amount of myocardial ischemia, often silent, compared with patients without diabetes. Furthermore, patients with coronary artery disease (CAD) and diabetes or insulin resistance have altered myocardial metabolism and accelerated and diffuse atherogenesis with involvement of distal coronary segments that causes chronic hypoperfusion and hibernation. Therefore, in patients with diabetes and CAD, the ischemic metabolic changes are heightened by the metabolic changes in patients with diabetes. An important metabolic alteration in patients with diabetes is the increase in free fatty acid (FFA) concentrations and the increased skeletal muscle and myocardial FFA uptake and oxidation. The increased uptake and utilization of FFA and the reduced utilization of glucose as a source of energy during stress and ischemia contribute to the increased susceptibility of diabetic hearts to myocardial ischemia and to a greater decrease of myocardial performance for a given amount of ischemia compared with nondiabetic hearts. A therapeutic approach aimed at an improvement in cardiac metabolism through manipulations of the use of metabolic substrates should result in an improvement in myocardial ischemia and left ventricular (LV) function. The inhibition of FFA oxidation with trimetazidine improves cardiac metabolism at rest, increases cardiac resistance to ischemia, and therefore reduces the decrease of LV function caused by chronic hypoperfusion and repetitive episodes of myocardial ischemia in patients with and without diabetes. Thus, modulation of myocardial FFA metabolism should be the key target for metabolic interventions in patients with CAD with and without diabetes. In patients with diabetes, the effects of modulation of FFA metabolism should be even greater compared with those observed in patients without diabetes. Because of its effect on cardiac metabolism at rest and its effects on myocardial ischemia and LV function, trimetazidine should always be considered for the treatment of patients with diabetes with CAD with or without LV dysfunction.

Short-Term Pioglitazone Treatment Improves Vascular Function Irrespective of Metabolic Changes in Patients With Type 2 Diabetes

To determine whether pioglitazone influences endothelial function directly, we examined in a randomized, crossover, placebo-controlled, double-blind trial the effects of 4 weeks of pioglitazone treatment in 20 male type 2 diabetic patients. We conclude that short-term pioglitazone treatment ameliorates endothelial dysfunction in conduit arteries irrespective of significant beneficial changes in plasma levels of insulin, FFA, adiponectin, or CRP in type 2 patients with diabetes. Pioglitazone, a PPARgamma agonist, not only improves insulin resistance and glycemic control but may also have additional beneficial vascular effects in patients with type 2 diabetes. Low-grade inflammation, free fatty acids, and adiponectin may play a role in modulation of vascular function. We studied the effect of 4 weeks of pioglitazone treatment on endothelial function, metabolic changes, and C-reactive protein in patients with type 2 diabetes. A randomized, crossover, placebo-controlled, double-blind trial was performed in which pioglitazone 30 mg once daily was administered to 20 patients with type 2 diabetes on oral antihyperglycemic agents for 4 weeks. Shear stress-induced flow-mediated dilation (FMD) of the brachial artery was used as outcome parameter for vascular function. Brachial artery endothelial function was significantly increased by pioglitazone treatment compared with placebo (FMD 5.4 +/- 0.5% versus 3.1 +/- 0.5%, P = 0.001). Endothelium-independent vasodilation was not different between the 2 study periods. Pioglitazone treatment reduced insulin, FFA, and C-reactive protein concentrations compared with placebo (18.3 +/- 2.4 versus 14.8 +/- 2.1 mU/L, P = 0.03; 641 +/- 46 versus 542 +/- 33 mumol/L, P = 0.04; and 3.5 +/- 0.6 mg/L versus 2.6 +/- 0.5 mg/L, P = 0.01; respectively). A significant increase in plasma adiponectin concentration (3.95 +/- 0.57 microg/mL versus 7.59 +/- 0.95 microg/mL, P = 0.002) was also observed. No correlations were found between these metabolic changes and the improvement of conduit artery endothelial function. Short-term pioglitazone treatment ameliorates endothelial dysfunction in conduit arteries irrespective of changes in insulin, FFA, adiponectin, or CRP in type 2 patients with diabetes.

Impact of Intraaortic Therapy on Metabolic Changes in Patients with Peritoneal Sepsis Complicated by Multiple Organ Dysfunction

The study was undertaken to analyze the parameters of metabolism and lipid peroxidation when intraaortic infusion therapy was used in combination with sodium hypochlorite. The time course of changes in lactate and glucose levels, appropriate indices, LPO/AOS parameters shows the preference of a complex of intraaortic therapy in the volume of 50—60 ml/kg/day and daily intraaortic injection of 400—500 ml of 0.06% sodium hypochlorite solution and 800 ml of reamberin to other modes of intraaortic correction of metabolic disturbances.

Metabolite Profile of Cerebrospinal Fluid in Patients With Spina Bifida: A Proton Magnetic Resonance Spectroscopy Study

The present study was carried out to assess the metabolic differences between cerebrospinal fluid samples of patients with spina bifida and age-matched control individuals. To study the metabolite profile of cerebrospinal fluid of patients with spina bifida using proton magnetic resonance spectroscopy, compare the levels of metabolites with controls, establish correlation of underlying neuronal dysfunction with metabolic changes in patients with spina bifida, and evaluate the potential use of this technique as an additional tool for diagnostic assessment. Combination of embryopathy, stretching, ischemia, compression, and trauma is responsible for cord dysfunction in spina bifida. Changes in neuronal metabolism leads to changes in the local milieu of cerebrospinal fluid in the cord. Change in metabolite profile of cerebrospinal fluid in spina bifida in terms of increase in products of anaerobic metabolism, nerve membrane integrity, and nerve ischemia has not yet been studied. Cerebrospinal fluid obtained from patients and control individuals were characterized using various one- and two-dimensional proton magnetic resonance spectroscopy techniques. Concentration of various metabolites was calculated using the area under the nuclear magnetic resonance peak. Statistically significantly higher levels of lactate, choline, glycerophosphocholine, acetate, and alanine in the cerebrospinal fluid of patients with spina bifida was observed compared with control individuals. Significantly higher levels of metabolites were observed in patients with spina bifida, representing a state of nerve ischemia, anaerobic metabolism, and disruption of neuronal membrane.

Cerebral hemodynamic and metabolic changes in patients with fulminant hepatic failure during liver transplantation

Background Cerebral autoregulation and metabolism may be seriously compromised in patients with fulminant hepatic failure (FHF). The mechanism responsible for the alteration in cerebral blood flow (CBF) has not been yet clearly defined; however, it is known that it does correlate with liver function. Orthotopic liver transplant (OLT) rapidly restores normal liver function, but little is known about the restoration of cerebral metabolism and hemodynamics. To investigate the relationship between liver function and CBF, we evaluated autoregulation and metabolic changes during OLT in six patients comatose due to FHF. Methods We evaluated autoregulation based on a linear regression analysis between mean arterial blood pressure and parallel CBF velocity (CBFV) changes using transcranial Doppler ultrasound. Cerebral metabolism rate was estimated by the arterial-jugular venous oxygen content difference (a-jDO 2), while the percentile variation in cerebral metabolic rate for oxygen (CMRO 2) was estimated using CBFV percentile variation rather than CBF percentile variation (eCMRO 2). Results Prior to transplant autoregulation was impaired in all patients. However it markedly improved at the end of surgery ( P < .05). The eCMRO 2 improved as well, particularly among subjects who displayed prompt neurological recovery. In all patients the a-jDO 2 was low before transplantation increasing to normal values at the end of surgery. Conclusions A hallmark of FHF seems to be failure of autoregulation, which is linked to uncoupling between CBF and CMRO 2 as attested by an a-jDO 2 lower than normal in all patients (luxury perfusion). The recovery of liver function rapidly improves cerebral hemodynamics and metabolic stability. The study of autoregulation and eCMRO 2 recovery using Doppler monitoring proffers the possibility to predict early graft function after liver reperfusion. In our patients eCMRO 2 seemed to be associated with improved neurological outcomes.

Similar 1H magnetic resonance spectroscopic metabolic pattern in the medial temporal lobes of patients with mild cognitive impairment and Alzheimer disease

Structures of the medial temporal lobes are recognized to play a central role in memory processing and to be the primary sites of deterioration in Alzheimer disease (AD). Mild cognitive impairment (MCI) represents potentially an intermediate state between normal aging and AD. Proton magnetic resonance spectroscopy (MRS) was used to examine brain metabolic changes in patients with AD and MCI in the medial temporal lobes (MTLs), parietotemporal cortices (PTCs) and prefrontal cortices (PFCs). Fourteen patients with MCI, 14 patients with mild AD and 14 age- and sex-matched control subjects were studied. Patients with AD and MCI demonstrated significant reductions of NAA/H 2O and Cho/H 2O in the left MTL relative to control subjects. Patients with AD showed mI/H 2O increases relative to patients with MCI and control subjects in all six regions investigated, and a statistically significant mI/H 2O increase was measured in the right PTC. Patients with AD and MCI demonstrated the same metabolic pattern in the left MTL, suggesting a similar pathological process underlying memory impairment. Increased mI signal appears to be a neurochemical abnormality associated mostly with AD and the dementia process. Some interhemispheric metabolite asymmetries were increased in AD patients.

Endogenous urinary steroids in premenopausal women with uterine leiomyomas

Objectives: To study the effect of endogenous steroids on the presence of uterine leiomyomas. Methods: Urine samples of 27 premenopausal women with leiomyomas and 25 age-matched healthy premenopausal women were collected. The concentration of estrogens and androgens in the urine samples of the two groups were determined using a gas chromatography mass spectrometer and the two groups were compared. To study metabolic changes in patients indirectly, the concentration ratios of precursor metabolite to product metabolite of the two groups were also compared. Results: Urinary concentrations of 17 β-estradiol, 5-androstene-3 β, 16 β, 17 β, triol, 11-keto-ethiocholanolone, 11 β-hydroxy-androsterone, 11 β-hydroxy-etiocholanolone, THS, THA, THE, α-cortol and β-cortol were significantly higher in patients than in controls. The concentration ratios of 17 β-estradiol/estrone and 11/ β-hydroxy-ethiocholanolone/11 β-hydroxy-androsterone increased in patients. Conclusions: The presence of uterine leiomyomas correlates with an increase in urinary concentrations of estrogens and androgens, and it appears to be caused by a decrease in patients’ metabolism of steroids.

“Change the mind and you change the brain”: effects of cognitive-behavioral therapy on the neural correlates of spider phobia

Questions pertaining to the neurobiological effects of psychotherapy are now considered among the most topical in psychiatry. With respect to this issue, positron emission tomography (PET) findings indicate that cognitive and behavioral modifications, occurring in a psychotherapeutic context, can lead to regional brain metabolic changes in patients with major depression or obsessive-compulsive disorder. The goal of the present functional magnetic resonance imaging (fMRI) study, which constitutes the first neuroimaging investigation of the effects of cognitive-behavioral therapy (CBT) using an emotional activation paradigm, was to probe the effects of CBT on the neural correlates of spider phobia. In order to do so, fMRI was used in subjects suffering from spider phobia ( n = 12) to measure, before and after effective CBT, regional brain activity during the viewing of film excerpts depicting spiders. Normal control subjects were also scanned (once) while they were exposed to the same film excerpts. Results showed that, in phobic subjects before CBT, the transient state of fear triggered, during the viewing of the phobogenic stimuli, was correlated with significant activation of the right dorsolateral prefrontal cortex (Brodmann area—BA 10), the parahippocampal gyrus, and the visual associative cortical areas, bilaterally. For normal control subjects ( n = 13), only the left middle occipital gyrus and the right inferior temporal gyrus were significantly activated. In phobic subjects before CBT, the activation of the dorsolateral prefrontal cortex (BA 10) may reflect the use of metacognitive strategies aimed at self-regulating the fear triggered by the spider film excerpts, whereas the parahippocampal activation might be related to an automatic reactivation of the contextual fear memory that led to the development of avoidance behavior and the maintenance of spider phobia. After successful completion of CBT, no significant activation was found in the dorsolateral prefrontal cortex (BA 10) or the parahippocampal gyrus. These findings suggest that a psychotherapeutic approach, such as CBT, has the potential to modify the dysfunctional neural circuitry associated with anxiety disorders. They further indicate that the changes made at the mind level, within a psychotherapeutic context, are able to functionally “rewire” the brain.

Increased fructose concentrations in blood and urine in patients with diabetes.

To investigate fructose metabolic changes in patients with diabetes. Serum and urinary fructose concentrations were determined in healthy subjects (n = 23) and in nondiabetic (n = 23) and diabetic patients (n = 26). Fructose was measured using our newly developed method, and (13)C(6)-fructose was used as the internal standard. After adding sample to a fixed amount of internal standard, ion-exchange resins and high-performance liquid chromatography pretreatments were performed. Then, the amount of fructose in the sample was measured by gas chromatography-mass spectrometry. Serum fructose concentrations in patients with diabetes (12.0 +/- 3.8 micromol/l) were significantly higher than those in healthy subjects (8.1 +/- 1.0 micromol/l, P < 0.001) and nondiabetic patients (7.7 +/- 1.6 micromol/l, P < 0.001), and daily urinary fructose excretion was significantly greater in patients with diabetes (127.8 +/- 106.7 micromol/day) than in nondiabetic patients (37.7 +/- 23.0 micromol/day, P < 0.001). In patients with diabetes (n = 20), serum fructose concentrations (8.6 +/- 1.8 micromol/l, P < 0.001) and daily urinary fructose excretion (63.4 +/- 63.8 micromol/day, P < 0.01) significantly decreased by week 2 after admission. The present results differed from those of previous studies in that we found that the serum and urinary fructose concentrations decreased rapidly, concomitant with an improvement in glycemia. Therefore, hyperglycemia was associated with increased serum and urinary fructose concentrations in patients with diabetes.

TREATMENT OF HAART-ASSOCIATED METABOLIC CHANGES IN PATIENTS WITH HIV INFECTION: DK-02-006

TREATMENT OF HAART-ASSOCIATED METABOLIC CHANGES IN PATIENTS WITH HIV INFECTION: DK-02-006

Treatment of Haart-Associated Metabolic Changes in Patients with HIV Infection

Treatment of Haart-Associated Metabolic Changes in Patients with HIV Infection

Treatment of Haart-Associated Metabolic Changes in Patients with HIV Infection

Treatment of Haart-Associated Metabolic Changes in Patients with HIV Infection

Hair repigmentation in lentigo maligna

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Cerebral metabolic changes in patients with a symptomatic occlusion of the internal carotid artery: a longitudinal 1H magnetic resonance spectroscopy study.

The objective of this 1H magnetic resonance spectroscopy study was to investigate the time course of the brain metabolites N-acetyl-aspartate (NAA), choline, and lactate in patients with transient or minor disabling neurological deficits associated with an occlusion of the internal carotid artery (ICA). Fifty patients had had symptoms of hemispheric ischemia, and 16 had suffered symptoms of retinal ischemia. Single-voxel proton spectra were obtained from uninfarcted cerebral regions on three occasions: 0-6, 6-12, and 12-18 months after symptoms. Reference values were obtained from 29 control subjects. In the 0-6 month period, patients with hemispheric ischemia showed a significantly lower NAA/creatine ratio in the hemisphere ipsilateral to the ICA occlusion, compared with control subjects and patients with retinal ischemia, and a significantly higher choline/creatine ratio, compared with control subjects. The prevalence of lactate did not differ significantly between patient groups. In the following time periods, the NAA/creatine ratio in patients with hemispheric ischemia tended to return to control values and no longer differed from that in patients with retinal ischemia; the choline/creatine ratio decreased significantly and returned to control values. These results demonstrate that cerebral metabolism is altered in patients with an ICA occlusion who have had a hemispheric ischemic event, but returns (choline) or tends to return (NAA) to control values over time. The metabolic changes occur primarily in the hemisphere ipsilateral to the symptomatic ICA occlusion and are related to the occurrence of the hemispheric ischemic event.

Compensatory mechanisms for chronic cerebral hypoperfusion in patients with carotid occlusion.

The purpose of this experiment was to assess long-term cerebral hemodynamic and metabolic changes in patients with increased oxygen extraction fraction (OEF) in the hemisphere distal to an occluded carotid artery who remain free of stroke. Methods--Ten patients with increased OEF and no interval stroke underwent repeated positron emission tomography examinations 12 to 59 months after the initial examination. Quantitative regional measurements of cerebral blood flow, cerebral blood volume, cerebral rate of oxygen metabolism (CMRO2), and OEF were obtained. Regional measurements of the cerebral rate of glucose metabolism (CMRGlc) were made on follow-up in 5 patients. Statistical significance (P<0.05) was measured with t tests and linear regression analysis. The ipsilateral/contralateral OEF ratio declined from a mean of 1.16 to 1.08 (P=0.022). Greater reductions were seen with longer duration of follow-up (P=0.023, r=0.707). The cerebral blood flow ratio improved from 0.81 to 0.85 (P=0.021). No change in cerebral blood volume or CMRO2 was observed. CMRGlc was reduced in the ipsilateral hemisphere (P=0.001 compared with normal), but the CMRO2/CMRGlc ratio was normal. Increased OEF improves in patients with carotid occlusion and no interval stroke. This improvement in OEF is due to an improvement in collateral blood flow.

Metabolic changes in patients with mitochondrial myopathies and effects of coenzyme Q10 therapy.

We used a standardized bicycle ergometry protocol with a stepwise increasing workload (30-100 W) to evaluate various metabolic factors for the diagnosis and metabolic monitoring of mitochondrial encephalomyopathies. All patients (n = 9) showed pathological venous lactate/pyruvate (L/P) ratios, which normalized in three patients after 6 months of coenzyme Q10 (CoQ) therapy. Thus, the L/P ratio proved to be the clinically most useful parameter in the evaluation and monitoring of mitochondrial diseases, showing higher sensitivity than lactate measurements only. CoQ may exert a favourable effect in some patients with mitochondrial diseases.