Skip to main content

Home/ Dr. Goodyear/ Group items tagged imaging

Rss Feed Group items tagged

Nathan Goodyear

Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumat... - 0 views

  • The changes in SPECT images after treatment indicate that HBOT led to reactivation of neuronal activity in stunned areas that seemed normal under CT and MRI imaging. While SPECT imaging has a limited spatial resolution (compared, for example, to fMRI), the changes in activity were sufficiently robust to be clearly detected by the SPECT images.
  • HBOT might initiate a cellular and vascular repair mechanism and improve cerebral vascular flow
  • HBOT induces regeneration of axonal white matter [61], [62], [63], [64], has positive effect upon the myelinization and maturation of injured neural fibers [65], and can stimulate axonal growth and increase the ability of neurons to function and communicate with each other
  • ...6 more annotations...
  • HBOT was found to have a role in initiation and/or facilitation of angiogenesis and cell proliferation processes needed for axonal regeneration [67].
  • The observed reactivation of neuronal activity in the stunned areas found here, along with similar results in post-stroke patients
  • At the cellular level, HBOT can improve cellular metabolism, reduce apoptosis, alleviate oxidative stress and increase levels of neurotrophins and nitric oxide through enhancement of mitochondrial function (in both neurons and glial cells)
  • HBOT may promote the neurogenesis of endogenous neural stem cells
  • With regard to secondary injury mechanisms in mTBI, HBOT can initiate vascular repair mechanism and improve cerebral vascular flow [58], [59], [68], [69], promote blood brain barrier integrity and reduce inflammatory reactions [28] as well as brain edema
  • It might be possible that HBOT enables the metabolic change simply by supplying the missing energy/oxygen needed for those regeneration processes.
  •  
    Hbot therapy, according to study, induces neuroplasticity and improves brain function in post concussion syndrome and those with mTBI.  The important point about this study was that the study was done years after the injury; what if the therapy was employed immediately after...
umar111

Computer Science: Computer hardware - 0 views

  •  
    Computer Science Tuesday, April 25, 2023 Computer hardware Computer hardware is the physical components that make up a computer system. It includes everything from the central processing unit (CPU) to the monitor, keyboard, and mouse. Understanding the different types of hardware and how they work together is essential for anyone who works with computers. In this article, we will explore the various components of computer hardware, including internal and external components, and the peripherals that connect to them. We will also discuss the importance of hardware maintenance, the latest advancements in computer technology, and factors to consider when choosing the right hardware for your needs. Whether you are a computer technician, a gamer, or simply someone who uses a computer for everyday tasks, this article will help you better understand the world of computer hardware. Introduction to Computer Hardware Computer hardware refers to the physical components that make up a computer system. It includes everything from the processor and memory to input/output devices such as the keyboard and monitor. In this article, we will explore the different types of computer hardware and their functions. What is Computer Hardware Computer hardware refers to the physical components of a computer system. It includes all the components that can be touched, seen, and used to interact with a computer, such as the monitor, keyboard, and mouse. Hardware is different from computer software, which refers to the programs and applications that run on a computer system. History of Computer Hardware The history of computer hardware dates back to the 1820s when Charles Babbage, an English mathematician, and inventor, designed the first analytical engine, which was considered to be the first mechanical computer. With time, more complex electronic computers were developed, including the first Intel microprocessor in 1971. Since then, computer hardware has continued to evolve, becoming
Nathan Goodyear

Imaging of bone metastasis: An update - 0 views

  •  
    Great review of imaging for bone metastasis.
Nathan Goodyear

Late Disseminated Lyme Disease: Associated Pathology and Spirochete Persistence Post-Tr... - 0 views

  • In this study, we have demonstrated microscopic pathology ranging from minimal to moderate in multiple different tissues previously reported to be involved with LD, including the nervous system (central and peripheral), heart, skeletal muscle, joint-associated tissues, and urinary bladder 12 to 13 months following tick-inoculation of rhesus macaques by Bb strain B31
  • Based on histomorphology, inflammation consisted predominantly of lymphocytes and plasma cells, with rare scattered histiocytes
  • in rare instances, morphologically intact spirochetes were observed in inflamed brain and heart tissue sections from doxycycline-treated animals
  • ...41 more annotations...
  • colocalization of the Bb 23S rRNA probe was not observed in any of the sections of experimental inoculated animals shown to harbor rare persistent spirochetes (Supplemental Figure S1). Previous in vitro work has shown large decreases in Bb rRNA levels when in a stationary phase of growth despite the majority of spirochetes remaining viable
  • The possibility that the spirochetes were intact but dead also exists, though this may be unlikely given the precedence for viable but non-cultivable B. burgdorferi post-treatment
  • The doxycycline dose utilized in this study (5mg/kg) was based on a previous pharmacokinetic analysis of oral doxycycline in rhesus macaques proven to be comparable to levels achieved in humans and was meant to mimic treatment of disseminated LD
  • In addition to the brain of two treated animals, rare morphologically intact spirochetes immunoreactive to OspA were observed in the heart of one treated animal
  • Although we did not measure the doxycycline levels in the cerebrospinal fluid, they have been found to be 12% to 15% of the amount measured in serum
  • We and others have demonstrated the development of a drug-tolerant persister population when B. burgdorferi are treated with antibiotics in vitro
  • The adoption of a dormant or slow-growing phenotype likely allows the spirochetes to survive and re-grow following removal of antibiotic
  • The basic premise that antibiotic tolerance may be an adaptation of the sophisticated stringent response required for the enzootic cycle by the spirochetes is described in a recent review as well
  • Although current IDSA guidelines recommend intravenous ceftriaxone (2g daily for 30 days) over oral doxycycline for treatment of neuroborreliosis, a randomized clinical trial failed to show any enhanced efficacy of I.V. penicillin G to oral doxycycline for treatment of Lyme neuroborreliosis (no treatment failures were reported in this study of 54 patients).
  • we can speculate that the minimal to moderate inflammation that was observed, especially within the CNS and PNS can, in part, explain the breadth of symptoms experienced by late stage Lyme disease patients, such as cognitive impairment and neuralgia.
  • Erythema migrans, the clinical hallmark of early localized Lyme disease, was observed in one of the rhesus macaques from this study.
  • In 2014, a trailblazing study in mice demonstrated a dramatic decline in B. burgdorferi DNA in the tissues for up to eight months after antibiotic treatment followed by the resurgence of B. burgdorferi growth 12 months after treatment
  • This study provides evidence that the slow-growing spirochetes which persist after treatment, but are not cultivable in standard growth media may remain viable.
  • The first well-documented indication of Lyme disease (LD) in the United States occurred in the early 1970s
  • Lyme, Connecticut.
  • Lyme disease is now known to be caused by multiple closely related genospecies classified within the Bb sensu lato complex, representing the most common tick-borne human disease in the Northern Hemisphere
  • approximately 30,000 physician-reported cases occur annually in the United States, the annual incidence has been estimated to be 10-fold higher by the Centers for Disease Control and Prevention.6
  • Current antibiotic therapy guidelines outlined by the Infectious Disease Society of America (IDSA) are successful in the treatment of LD for the majority of LD patients, especially when administered early in disease immediately following identification of erythema migrans (EM)
  • ‘post-treatment Lyme disease syndrome’ (PTLDS)
  • host-adapted spirochetes that persist in the tissues, probably in small numbers, inaccessible or impervious to antibiotic
  • inflammatory responses to residual antigens from dead organisms
  • residual tissue damage following pathogen clearance;
  • autoimmune responses, possibly elicited by antigenic mimicry
  • Experimental studies on immunocompetent mice, dogs, and rhesus macaques have provided evidence for the persistence of Bb spirochetes subsequent to antibiotic treatment in the form of residual spirochetes detected within tissue by IFA and PCR, and recovered by xenodiagnoses
  • Ten male rhesus macaques
  • half (five) of the NHP received antibiotic treatment, consisting of 5 mg/kg oral doxycycline twice per day.
  • Minimal and focal lymphoplasmacytic inflammation
  • inflammation was observed in the leptomeninges overlying a section of temporal cerebral cortex
  • Minimal localized lymphoplasmacytic choroiditis
  • Peripheral nerves contained minimal to moderate lymphoplasmacytic inflammation with a predilection for collagen-rich epineurium and perivascular spaces
  • Inflammation was observed in 56% (5/9) of the NHPs irrespective of treatment group
  • For all animals, inflammation was reserved to perineural tissue
  • The treatment lasted 28 days
  • Minimal to mild lymphoplasmacytic inflammation of either the myocardial interstitium (Figure 2Figure 2A), pericardium (Figure 2Figure 2B), or combination therein was observed in 60% of NHPs
  • A single morphologically intact spirochete, as indicated by positive red immunofluorescence (Figure 2Figure 2C), was observed in the myocardium of one treated animal
  • mild, multifocal lymphoplasmacytic inflammation was observed in one doxycycline-treated animal
  • three animals exhibited minimal to mild lymphoplasmacytic inflammation affecting joint-associated structures
  • 10% to -20% of human patients treated
  • Multiple randomized placebo-controlled studies which evaluated sustained antimicrobial therapy concluded that there is no benefit in alleviating patients’ symptoms and indicated that long-term antibiotic therapy may even be detrimental to patients due to potential associated complications (ie, catheter infection and/or clostridial colitis)
  • and the rapid clearance of dead spirochetes in a murine model
  • higher doses may be needed to combat neuroborreliosis
  •  
    persistent borrelia burgdorferia were found in the brain (2) and the heart (1) up to 13 months post standard antibiotic treatment suggesting borrelia burdorferia, the cause of Lyme, can persist in a chronic, persistant state poste acute treatment.
Nathan Goodyear

The Ketogenic Diet and Sport: A Possible Marriage? : Exercise and Sport Sciences Reviews - 0 views

  • It is important to note that, although the blood level of glucose drops, it still remains at a physiological level (23), which is maintained through gluconeogenesis involving glucogenic amino acids and also glycerol released from triglycerides
  • “physiological ketosis” where KB levels may rise to 7 to 8 mmol L-1 (but without any pH change). In “pathological diabetic ketoacidosis,” on the other hand, ketonemia can exceed 20 mmol L-1 and also cause lowering of blood pH
  • in the initial phase of KD, about 16% of glucose comes from glycerol (released from triglyceride hydrolysis) and the bulk (60–65 g) from proteins via gluconeogenesis (proteins may be of either dietary or endogenous origin
  • ...5 more annotations...
  • the protein supply consumed during a KD “preserves,” as demonstrated, lean body mass
  • The importance of glycerol as a glucose source increases progressively during ketosis; in fact, glycerol passes from supplying 16% of total glucose to an average of 60% after many days (>7 d) of complete fasting (from 38% in lean individual to 79% in the obese).
  • The possible reasons for the effectiveness of KD for weight loss may be listed as follows, in order of evidence, strongest first: Figure 3Image Tools 1. Appetite reduction: protein satiety, effects on appetite-related hormones such as ghrelin, and possibly a sort of direct appetite-blocking effect of KB 2. Reduced lipogenesis and increased fat oxidation 3. A reduction in respiratory quotient may indicate a greater metabolic efficiency in fat oxidation 4. A thermic effect of proteins and increased energy usage by gluconeogenesis
  • all data regarding biochemical and molecular mechanisms suggest that it is very difficult to increase muscle mass during a KD; use of which really should be limited to the few days immediately before competition in bodybuilding.
  • a long-term KD can interfere with some muscle hypertrophy mechanisms and this could be counterproductive if the aim of the athlete is to gain muscle mass
  •  
    Great read on the ketogenic  and its application to sports/training...
Nathan Goodyear

Pictorial Review of Glutamate Excitotoxicity: Fundamental Concepts for Neuroimaging - 0 views

  •  
    excellent article on the imaging of excitotoxicity.  Glutamate excitotoxicity is a key component in neurodegenerative diseases: Alzheimers, Parkinsons, ALS, MS...
Abdullah Kul

Phen375 Phentemine Fat Burner - 0 views

  •  
    Phen375 is a pharmacy grade food supplement with diet program included - both extensive diet plans and exercise video instructions. It is great choice for people who look for that extra to help them with losing weight and getting motivation. Phen375 is food supplement and would greatly compliment your existing weight loss and dieting promotions (especially those attracting American search traffic). Why to promote Phen375 - Most paying weight loss sector merchant - One of highest EPC amongst diet products - Most profitable merchant for the affiliates in 2011, 2012 and 2013 - Reorder ratios ranging between 21- 33% - Top range conversion rates Phen375 offers highly converting website, ensuring you get highest return possible on your traffic. Also you will find wealth of resources, such as articles, product images and banners to help with your promotions. Also if you have any questions or need help with promotions, please contact Phen375's dedicated affiliate manager - Catherine Day. You can see her details on the right.
Dr. Jennifer Martinick

Dr Jennifer Martinick Reviews: Client Results - 0 views

  •  
    Dr Jennifer Martinick of Martinick Hair Restoration Clinics shares her Client reviews and Image results as proof of her brilliant work.
Nathan Goodyear

http://www.uclouvain.be/cps/ucl/doc/ir-ldri/images/BINDELS2013IJBCLB.pdf - 0 views

  •  
    gut microflora and its impact on muscle loss/muscle growth.  Not just for lean versus fat evaluation.
Nathan Goodyear

KoreaMed Synapse - 0 views

  •  
    Nice image that clearly depicts aerobic glycolysis and more, the effects of HIF-1alpha due to hypoxia.
Nathan Goodyear

Production of bilirubin with hemolysis | eClinpath - 0 views

  •  
    Good image of bilibrubin metabolism with hemolysis.
Nathan Goodyear

Role of maximum standardized uptake value in fluorodeoxyglucose positron emission tomog... - 0 views

  • 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is an effective and popular technique for evaluating patients before and after breast cancer surgery.
  • Quantitative FDG-PET/CT imaging is becoming prevalent in cancer treatment as it measures glucose metabolism that reflects the growth potential and metabolic activity of malignant tumors
  • The FDG-PET/CT findings of primary lesions in colorectal and lung cancers correlate with metastasis and prognosis because FDG reflects tumor viability
  • ...15 more annotations...
  • The technique is valuable for predicting the prognosis of patients with recurrent breast cancer and for determining and predicting the outcomes of neoadjuvant chemotherapy
  • FDG-PET/CT is useful not only for evaluating metastasis but also for predicting the prognosis of recurrent breast cancer and measuring treatment effects
  • reports remain limited to small-scale clinical trials of about 100 patients.
  • MaxSUV, which is the most popular FDG-PET/CT value, can vary up to 30 % because of differences among PET/CT devices and among the operators who create the images
  • the degree of malignancy would increase with an increase in maxSUV when ER or HER-2 signaling is involved.
  • Factors that determine the rate of cancer progression include T-factor (tumor diameter) and N-factor (presence or absence/number of lymph node metastasis)
  • The prognostic factors applied in breast cancer can be broadly divided into those that determine staging and those that determine biological tumor characteristics
  • Prognosis was previously predicted based on T, N, and M staging, which indicates the degree of progression. However, prognosis is now predicted and treatment regimes are presently selected by also considering ER and HER-2 levels, which determine the nature of the tumor
  • maxSUV presently serves as an indicator of metabolic activity during cancer therapy. For instance, the maxSUV of primary lung and hematological cancer lesions correlates with metastasis and prognosis, whereas maxSUV also seems useful for predicting the prognosis of recurrent breast cancer and in determining and predicting the outcome of neoadjuvant chemotherapy
  • The maxSUV cut-off calculated from ROC curves for recurrence was 3.0
  • Factors that determine the nature of tumors also include ER, HER-2, Ki-67 labeling index, and nuclear grade
  • both ER status and maxSUV as independent prognostic factors
  • maxSUV has a closer correlation with prognosis
  • maxSUV, clinical T-factor and ER were significant prognostic factors
  • Our results showed that maxSUV has the potential to be a novel prognostic factor and that it can be used to determine future therapies
  •  
    Retrospective, multi-facility finds maxSUV can be used in prognosis in cancer.  Others have shown benefit in recurrence risk.  MaxSUV was found to be an independent factor.
Nathan Goodyear

Evaluation of FLT-PET-CT as an imaging biomarker of proliferation in primary breast can... - 0 views

  • We have demonstrated that the majority of patients have a sizeable reduction in SUVmax from a single cycle of NAC with a mean change of −32.3%
  • This study, however, failed to show any predictive markers of response after one cycle of chemotherapy
  • These data therefore suggest that the main utility of FLT-PET as an imaging biomarker in early breast cancer is pre-chemotherapy, as a marker of proliferation, rather than in predicting pathological response after chemotherapy
  • ...2 more annotations...
  • In terms of the histological proliferation biomarker Ki-67, we have shown a good correlation with FLT-PET pre-chemotherapy. The best predictive marker of response in terms of pCR was baseline Ki-67
  • Our study has shown that baseline Ki-67 and FLT SUVmax is well correlated in keeping with FLT-PETs status as a proliferation biomarker, although Ki-67 had a better predictive ability in terms of pathological outcome
  •  
    PET CT scan shown to be useful as a proliferation biomarker pre-chemo in breast cancer.
Nathan Goodyear

FDG-PET/CT imaging biomarkers in head and neck squamous cell carcinoma - 0 views

  • F-fluoro-2-deoxyglucose (FDG) PET/CT is sensitive for the diagnosis and initial staging of several types of malignancies
  • SUV is a semiquantitative measure of the normalized concentration of radioactivity in a tumor or lesion
  • As FDG is the most common radiotracer used clinically and reflects tumor glucose metabolism, SUV is used as a surrogate marker for tumor metabolism.
  • ...9 more annotations...
  • The association between FDG uptake and tumor burden or stage has been well documented
  • advanced tumors tend to have higher FDG uptake (and thus higher SUV values)
  • the impact of the SUV on treatment outcome has been observed even within a given tumor stage
  • primary tumor SUVmax >10 predicted survival, independent of the tumor stage and diameter
  • FDG uptake not only reflects tumor burden/stage but also expresses, at least in part, some intrinsic biologic characteristic(s) of the tumor
  • SUVmax reflects the highest voxel value within the ROI or VOI. It is the most widely used parameter to measure metabolic tumor activity in oncologic FDG-PET/CT imaging
  • Several studies suggest that primary tumor baseline SUVmax also has predictive value in assessing the tumor burden, lymph node involvement and local extension
  • According to EORTC, a drop (delta between baseline and post-therapy) of 15–25% in SUVmax may represent a good treatment response
  • PERCIST criteria was proposed by the investigators at the Johns Hopkins Medical Institutions and suggested that a decrease in SUV normalized to lean body mass of at least 30% should be achieved before considering partial tumor response
  •  
    Good review of PET/CT scan and MaxSUV in head and neck cancers.
Nathan Goodyear

How We Read Oncologic FDG PET/CT | Cancer Imaging | Full Text - 0 views

  • In early PET literature focusing on analysis of solitary pulmonary nodules, some researchers defined malignancy based on a SUVmax threshold of greater than 2.5
  • We contend that SUV analysis has virtually no role in this setting.
  • tumours grow as spheres, whereas inflammatory processes are typically linear
  • ...35 more annotations...
  • Far more important than the SUVmax is the pattern rather than intensity of metabolic abnormality and the correlative CT findings
  • Descriptively, we define SUV < 5 as “low intensity”, 5–10 as “moderate”, 10–15 as “intense” and >15 as “very intense”
  • Evolving literature suggests that intensity of uptake is an independent prognostic factor and in some tumour subtypes superior to histopathologic characterisation.
  • aerobic glycolysis
  • Our practice of thresholding the grey and colour scale to liver as detailed above results in similar image intensity to a fixed upper SUV threshold of 8 to 10
  • The advantage of using the liver as a reference tissue is also aided by this organ having rather low variability in metabolic activity
  • When the liver is abnormal and cannot be used as a reference organ, we use the default SUV setting of an upper SUV threshold of 8
  • One of the most challenging aspects of oncologic FDG PET/CT review, however, is to recognise all the patterns of metabolic activity that are not malignant and which consequently confound interpretation
  • Many benign and inflammatory processes are also associated with high glycolytic activity
  • Future articles in the “How I Read” series will address the specific details of reading PET/CT in various cancers
  • The intensity of uptake in metastases usually parallels that in the primary site of disease
  • For example, discordant low-grade activity in an enlarged lymph node in the setting of intense uptake in the primary tumour suggests it is unlikely malignant and more likely inflammatory or reactive
  • By CT criteria the enlarged node is ‘pathologic’ but the discordantly low metabolic signature further characterises this is as non-malignant since such a node is not subject to partial volume effects and therefore the intensity of uptake should be similar to the primary site
  • The exception is when the lymph node is centrally necrotic as a small rim of viable tumour is subject to partial volume effects with expectant lower intensity of uptake; integrating the CT morphology is therefore critical to reaching an accurate interpretation
  • Small nodes that are visualised on PET are conversely much more likely to be metastatic as such nodes are subject to partial volume effects.
  • The exception to this rule is tumours with a propensity for tumour heterogeneity at different sites
  • The combination of FDG and a more specific tracer, which visualises the well-differentiated disease can be very useful to characterise this phenomenon
  • “metabolic signature”
  • For the majority of malignant processes, the intensity of metabolic abnormality correlates with degree of aggressiveness or proliferative rate.
  • a negative PET/CT study in a patient with biopsy proven malignancy would be considered false-negative
  • Warburg effect
  • There, however, are a significant minority of tumours that utilise substrates other glucose such as glutamine or fatty acids as a source of the carbon atoms required for growth and proliferation
  • This includes a subset of diffuse gastric adenocarcinomas, signet cell colonic adenocarcinomas and some sarcomas, particularly liposarcoma
  • There may be a role for other radiotracers such as fluorothymidine (FLT) or amino acid substrates in this setting.
  • Some tumours harbour mutations that result in defective aerobic mitochondrial energy metabolism, effectively simulating the Warburg effect
  • patients with hereditary paraganglioma and pheochromocytoma highlight this phenomenon
  • These have intense uptake on FDG PET/CT despite often having low proliferative rate.
  • Uterine fibroids, hepatic adenomas, fibroadenomas of the breast and desmoid tumours are benign or relatively benign lesions that can have quite high FDG-avidity.
  • Metabolic activity switches off rapidly following initiation of therapy
  • Common examples where patients have commenced active therapy but the referrer is requesting “staging” includes hormonal therapy (eg. tamoxifen) in breast cancer, oral capecitabine in colorectal cancer or high dose steroids in Hodgkin’s lymphoma
  • It is therefore critical to perform PET staging before commencement of anti-tumour therapy
  • The potential advantage of routine diagnostic CT is improved anatomic localisation and definition
  • Without intravenous contrast, additional identification of typical oncologic complications such as pulmonary embolism or venous thrombosis cannot be identified
  • If the study is performed as an “interim” restaging study after commencement of therapy but before completion, in order to reach a valid or clinically useful conclusion findings must be interpreted in the context of known changes that occur at a specific timing and type of therapy
  • The most well studied use of interim PET is in Hodgkin’s lymphoma where repeat PET after two cycles of ABVD-chemotherapy provides powerful prognostic information and may improve outcomes by enabling early change of management
  •  
    good read on the PET/CT scan reading.  They mention that tumors are spheres and inflammation is linear, yet inflammation coexists with cancer; hard to simply delineate these on simple terms. I do agree aon the metabolic signature of the PET/CT scan
Nathan Goodyear

PET/CT Standardized Uptake Values (SUVs) in Clinical Practice and Assessing Response to... - 0 views

  • use of PET in clinical research, clinical trials, and drug discovery
  • use of PET/CT in assessing response to therapy
  • In some cases, such as Hodgkins lymphoma, quantitative PET/CT imaging may not actually be needed, as success can be defined by the complete absence of tracer uptake in the PET image following a course of standardized therapy
  • ...9 more annotations...
  • The utilization of PET/CT to assess response to therapy is increasing in the US related, in part, to the creation and subsequent favorable results of the National Oncologic PET Registry (NOPR)
  • Changes in size as a result of therapy may take many months to develop and any opportunity to make early decisions about therapy success or failure is often unduly delayed or lost altogether
  • measures of changes in metabolic activity via FDG PET/CT can provide an alternate approach to assess response to therapy -- often very early in the course of treatment
  • Current recommendations are that tumor SUVs should be reported
  • The true tracer uptake in a patient is composed of two components: the first being the amount of tracer uptake (e.g. FDG) associated with the disease status (the signal of interest), which can be modified by the biophysiological status of the patient. One of the more important patient parameters is the blood glucose level, which has been shown to inversely-linearly affect SUVs
  • A prospective study by Crippa et al.30 in eight patients showed that as blood glucose levels were increased from 92.4 ±10.2 to 158 ± 13.8 mg/100 ml by glucose loading, the average SUV of 20 liver metastases decreased from 9.4 ± 5.7 to 4.3 ± 8.3
  • chemotherapy can result in impaired renal function, significantly reducing the clearance of plasma FDG through the kidney and thus increasing tumor SUV relative to an initial PET scan
  • The second component of the true tracer uptake is biological variability
  • The biological variability has been estimated in several test-retest studies7,32–35 at approximately 10% for scans repeated within a few days
  •  
    Good review of the SUVs of a PET/CT scan.
Nathan Goodyear

Press-pulse: a novel therapeutic strategy for the metabolic management of cancer | Nutr... - 0 views

  • A “press” disturbance was considered a chronic environmental stress on all organisms in an ecological community
  • “pulse” disturbances were considered acute events that disrupted biological communities to produce high mortality
  • Neoplasia involving dysregulated cell growth is the biological endpoint of the disease
  • ...84 more annotations...
  • Data from the American Cancer Society show that the rate of increase in cancer deaths/year (3.4%) was two-fold greater than the rate of increase in new cases/year (1.7%) from 2013 to 2017
  • cancer is predicted to overtake heart disease as the leading cause of death in Western societies
  • cancer can also be recognized as a metabolic disease.
  • glucose is first split into two molecules of pyruvate through the Embden–Meyerhof–Parnas glycolytic pathway in the cytosol
  • Aerobic fermentation, on the other hand, involves the production of lactic acid under normoxic conditions
  • persistent lactic acid production in the presence of adequate oxygen is indicative of abnormal respiration
  • Otto Warburg first proposed that all cancers arise from damage to cellular respiration
  • The Crabtree effect is an artifact of the in vitro environment and involves the glucose-induced suppression of respiration with a corresponding elevation of lactic acid production even under hyperoxic (pO2 = 120–160 mmHg) conditions associated with cell culture
  • the Warburg theory of insufficient aerobic respiration remains as the most credible explanation for the origin of tumor cells [2, 37, 51, 52, 53, 54, 55, 56, 57].
  • The main points of Warburg’s theory are; 1) insufficient respiration is the predisposing initiator of tumorigenesis and ultimately cancer, 2) energy through glycolysis gradually compensates for insufficient energy through respiration, 3) cancer cells continue to produce lactic acid in the presence of oxygen, and 4) respiratory insufficiency eventually becomes irreversible
  • Efraim Racker coined the term “Warburg effect”, which refers to the aerobic glycolysis that occurs in cancer cells
  • Warburg clearly demonstrated that aerobic fermentation (aerobic glycolysis) is an effect, and not the cause, of insufficient respiration
  • all tumor cells that have been examined to date contain abnormalities in the content or composition of cardiolipin
  • The evidence supporting Warburg’s original theory comes from a broad range of cancers and is now overwhelming
  • respiratory insufficiency, arising from any number mitochondrial defects, can contribute to the fermentation metabolism seen in tumor cells.
  • data from the nuclear and mitochondrial transfer experiments suggest that oncogene changes are effects, rather than causes, of tumorigenesis
  • Normal mitochondria can suppress tumorigenesis, whereas abnormal mitochondria can enhance tumorigenesis
  • In addition to glucose, cancer cells also rely heavily on glutamine for growth and survival
  • Glutamine is anapleurotic and can be rapidly metabolized to glutamate and then to α-ketoglutarate for entry into the TCA cycle
  • Glucose and glutamine act synergistically for driving rapid tumor cell growth
  • Glutamine metabolism can produce ATP from the TCA cycle under aerobic conditions
  • Amino acid fermentation can generate energy through TCA cycle substrate level phosphorylation under hypoxic conditions
  • Hif-1α stabilization enhances aerobic fermentation
  • targeting glucose and glutamine will deprive the microenvironment of fermentable fuels
  • Although Warburg’s hypothesis on the origin of cancer has created confusion and controversy [37, 38, 39, 40], his hypothesis has never been disproved
  • Warburg referred to the phenomenon of enhanced glycolysis in cancer cells as “aerobic fermentation” to highlight the abnormal production of lactic acid in the presence of oxygen
  • Emerging evidence indicates that macrophages, or their fusion hybridization with neoplastic stem cells, are the origin of metastatic cancer cells
  • Radiation therapy can enhance fusion hybridization that could increase risk for invasive and metastatic tumor cells
  • Kamphorst et al. in showing that pancreatic ductal adenocarcinoma cells could obtain glutamine under nutrient poor conditions through lysosomal digestion of extracellular proteins
  • It will therefore become necessary to also target lysosomal digestion, under reduced glucose and glutamine conditions, to effectively manage those invasive and metastatic cancers that express cannibalism and phagocytosis.
  • Previous studies in yeast and mammalian cells show that disruption of aerobic respiration can cause mutations (loss of heterozygosity, chromosome instability, and epigenetic modifications etc.) in the nuclear genome
  • The somatic mutations and genomic instability seen in tumor cells thus arise from a protracted reliance on fermentation energy metabolism and a disruption of redox balance through excess oxidative stress.
  • According to the mitochondrial metabolic theory of cancer, the large genomic heterogeneity seen in tumor cells arises as a consequence, rather than as a cause, of mitochondrial dysfunction
  • A therapeutic strategy targeting the metabolic abnormality common to most tumor cells should therefore be more effective in managing cancer than would a strategy targeting genetic mutations that vary widely between tumors of the same histological grade and even within the same tumor
  • Tumor cells are more fit than normal cells to survive in the hypoxic niche of the tumor microenvironment
  • Hypoxic adaptation of tumor cells allows for them to avoid apoptosis due to their metabolic reprograming following a gradual loss of respiratory function
  • The high rates of tumor cell glycolysis and glutaminolysis will also make them resistant to apoptosis, ROS, and chemotherapy drugs
  • Despite having high levels of ROS, glutamate-derived from glutamine contributes to glutathione production that can protect tumor cells from ROS
    • Nathan Goodyear
       
      reason to eliminate glutamine in cancer patients and even GSH with cancer patients
  • It is clear that adaptability to environmental stress is greater in normal cells than in tumor cells, as normal cells can transition from the metabolism of glucose to the metabolism of ketone bodies when glucose becomes limiting
  • Mitochondrial respiratory chain defects will prevent tumor cells from using ketone bodies for energy
  • glycolysis-dependent tumor cells are less adaptable to metabolic stress than are the normal cells. This vulnerability can be exploited for targeting tumor cell energy metabolism
  • In contrast to dietary energy reduction, radiation and toxic drugs can damage the microenvironment and transform normal cells into tumor cells while also creating tumor cells that become highly resistant to drugs and radiation
  • Drug-resistant tumor cells arise in large part from the damage to respiration in bystander pre-cancerous cells
  • Because energy generated through substrate level phosphorylation is greater in tumor cells than in normal cells, tumor cells are more dependent than normal cells on the availability of fermentable fuels (glucose and glutamine)
  • Ketone bodies and fats are non-fermentable fuels
  • Although some tumor cells might appear to oxidize ketone bodies by the presence of ketolytic enzymes [181], it is not clear if ketone bodies and fats can provide sufficient energy for cell viability in the absence of glucose and glutamine
  • Apoptosis under energy stress is greater in tumor cells than in normal cells
  • A calorie restricted ketogenic diet or dietary energy reduction creates chronic metabolic stress in the body
  • . This energy stress acts as a press disturbance
  • Drugs that target availability of glucose and glutamine would act as pulse disturbances
  • Hyperbaric oxygen therapy can also be considered another pulse disturbance
  • The KD can more effectively reduce glucose and elevate blood ketone bodies than can CR alone making the KD potentially more therapeutic against tumors than CR
  • Campbell showed that tumor growth in rats is greater under high protein (>20%) than under low protein content (<10%) in the diet
  • Protein amino acids can be metabolized to glucose through the Cori cycle
  • The fats in KDs used clinically also contain more medium chain triglycerides
  • Calorie restriction, fasting, and restricted KDs are anti-angiogenic, anti-inflammatory, and pro-apoptotic and thus can target and eliminate tumor cells through multiple mechanisms
  • Ketogenic diets can also spare muscle protein, enhance immunity, and delay cancer cachexia, which is a major problem in managing metastatic cancer
  • GKI values of 1.0 or below are considered therapeutic
  • The GKI can therefore serve as a biomarker to assess the therapeutic efficacy of various diets in a broad range of cancers.
  • It is important to remember that insulin drives glycolysis through stimulation of the pyruvate dehydrogenase complex
  • The water-soluble ketone bodies (D-β-hydroxybutyrate and acetoacetate) are produced largely in the liver from adipocyte-derived fatty acids and ketogenic dietary fat. Ketone bodies bypass glycolysis and directly enter the mitochondria for metabolism to acetyl-CoA
  • Due to mitochondrial defects, tumor cells cannot exploit the therapeutic benefits of burning ketone bodies as normal cells would
  • Therapeutic ketosis with racemic ketone esters can also make it feasible to safely sustain hypoglycemia for inducing metabolic stress on cancer cells
    • Nathan Goodyear
       
      Ketones are much more than energy adaptabilit, but actually are therapeutic.
  • ketone bodies can inhibit histone deacetylases (HDAC) [229]. HDAC inhibitors play a role in targeting the cancer epigenome
  • Therapeutic ketosis reduces circulating inflammatory markers, and ketones directly inhibit the NLRP3 inflammasome, an important pro-inflammatory pathway linked to carcinogenesis and an important target for cancer treatment response
  • Chronic psychological stress is known to promote tumorigenesis through elevations of blood glucose, glucocorticoids, catecholamines, and insulin-like growth factor (IGF-1)
  • In addition to calorie-restricted ketogenic diets, psychological stress management involving exercise, yoga, music etc. also act as press disturbances that can help reduce fatigue, depression, and anxiety in cancer patients and in animal models
  • Ketone supplementation has also been shown to reduce anxiety behavior in animal models
  • This physiological state also enhances the efficacy of chemotherapy and radiation therapy, while reducing the side effects
  • lower dosages of chemotherapeutic drugs can be used when administered together with calorie restriction or restricted ketogenic diets (KD-R)
  • Besides 2-DG, a range of other glycolysis inhibitors might also produce similar therapeutic effects when combined with the KD-R including 3-bromopyruvate, oxaloacetate, and lonidamine
    • Nathan Goodyear
       
      oxaloacetate is a glycolytic inhibitor, as is doxycycline, and IVC.
  • A synergistic interaction of the KD diet plus radiation was seen
  • It is important to recognize, however, that the radiotherapy used in glioma patients can damage the respiration of normal cells and increase availability of glutamine in the microenvironment, which can increase risk of tumor recurrence especially when used together with the steroid drug dexamethasone
  • Poff and colleagues demonstrated that hyperbaric oxygen therapy (HBOT) enhanced the ability of the KD to reduce tumor growth and metastasis
  • HBOT also increases oxidative stress and membrane lipid peroxidation of GBM cells in vitro
  • The effects of the KD and HBOT can be enhanced with administration of exogenous ketones, which further suppressed tumor growth and metastasis
  • Besides HBOT, intravenous vitamin C and dichloroacetate (DCA) can also be used with the KD to selectively increase oxidative stress in tumor cells
  • Recent evidence also shows that ketone supplementation may enhance or preserve overall physical and mental health
  • Some tumors use glucose as a prime fuel for growth, whereas other tumors use glutamine as a prime fuel [102, 186, 262, 263, 264]. Glutamine-dependent tumors are generally less detectable than glucose-dependent under FDG-PET imaging, but could be detected under glutamine-based PET imaging
  • GBM and use glutamine as a major fuel
  • Many of the current treatments used for cancer management are based on the view that cancer is a genetic disease
  • Emerging evidence indicates that cancer is a mitochondrial metabolic disease that depends on availability of fermentable fuels for tumor cell growth and survival
  • Glucose and glutamine are the most abundant fermentable fuels present in the circulation and in the tumor microenvironment
  • Low-carbohydrate, high fat-ketogenic diets coupled with glycolysis inhibitors will reduce metabolic flux through the glycolytic and pentose phosphate pathways needed for synthesis of ATP, lipids, glutathione, and nucleotides
  •  
    Cancer is a mitochondrial disease? So says the well published Dr Seyfried. Glucose and glutamine drive cancer growth.
Nathan Goodyear

High dose intravenous vitamin c and metastatic pancreatic cancer: Two cases - 0 views

  •  
    2 case studies of high dose vitamin C in pancreatic cancer with good results.  The important thing here is the imaging and biomarkers were initiated and followed.  Progressive cancers, like pancreatic cancer, require more frequent dosing of IVC.
indiacardiacsurg

Dr. T S Kler Predict Contrast-Associated Kidney Injury After Percutaneous Coronary Inte... - 0 views

  •  
    Dr. T S Kler Best cardiologist Delhi uses x-ray imaging, known as angiography, to determine which arteries have the most intense blockages, and inject a fluid referred to the as iodinated evaluation into the bloodstream to make the blockages seen on x-ray. That fluid is toxic, and high-risk agencies could have kidney issues as an end result. For Consultation Dr.TS Kler Email - drtskler@indiacardiacsurgerysite.com Call for Appointment- +91-9370586696
‹ Previous 21 - 40 of 67 Next › Last »
Showing 20 items per page