Effects Of Various Therapeutic Interventions Research Articles

Model order reduction and sensitivity analysis for complex heat transfer simulations inside the human eyeball.

Heat transfer in the human eyeball, a complex organ, is significantly influenced by various pathophysiological and external parameters. Particularly, heat transfer critically affects fluid behavior within the eye and ocular drug delivery processes. Overcoming the challenges of experimental analysis, this study introduces a comprehensive three-dimensional mathematical and computational model to simulate the heat transfer in a realistic geometry. Our work includes an extensive sensitivity analysis to address uncertainties and delineate the impact of different variables on heat distribution in ocular tissues. To manage the model's complexity, we employed a very fast model reduction technique with certified sharp error bounds, ensuring computational efficiency without compromising accuracy. Our results demonstrate remarkable consistency with experimental observations and align closely with existing numerical findings in the literature. Crucially, our findings underscore the significant role of blood flow and environmental conditions, particularly in the eye's internal tissues. Clinically, this model offers a promising tool for examining the temperature-related effects of various therapeutic interventions on the eye. Such insights are invaluable for optimizing treatment strategies in ophthalmology.

Validation of the Greek version of the Binge Eating Scale in a sample of binge eating disorder patients.

Binge eating disorder (BED), the most prevalent eating disorder, carries significant physical and psychological consequences. Therefore, there is a continuous need to assess binge eating symptomatology and evaluate the effectiveness of various therapeutic interventions. The Binge Eating Scale (BES), which is a self-administered questionnaire, is widely used to assess binge eating in obese people. It examines the person' s experience of binge eating and the emotional, cognitive, and behavioural symptoms associated with it. The purpose of the present study was to translate and adapt BES in Greek, as well as to assess the factorial structure of BES and evaluate its psychometric properties. A sample of 160 participants (90% females) with a mean age of 40.7 years (SD=11.5 years) and a mean body mass index (BMI) 37.5kg/m2 (SD=9.2kg/m2) completed the BES and the Eating Disorder Examination Questionnaire (EDE-Q). An exploratory factor analysis (EFA) was carried out to assess the construct validity of the BES in a sample of patients with BED according to DSM-5 who came for therapy at the Eating Disorders Unit at Eginition Hospital and the day center "Anasa". The two-factor structure fits the data best. Regarding internal consistency, the results were acceptable, with Cronbach' s alpha equal to 0.78. The BES has high significant correlations with the Eating Concern, Weight Concern, and Shape Concern subscales and the Global Score of EDE-Q, but not with the Restrain subscale. Also, BES has correlations with the specific EDE-Q questions about the frequency of objective and subjective binge eating episodes. A high correlation was obtained with the measure of ΒΜΙ too. The Greek version of BES is a valid and reliable scale to evaluate binge eating in a clinical population diagnosed with BED.

Quality of Life: A Comprehensive Review on Impact of Interventions among Breast Cancer Patients

ABSTRACT The effect of various therapeutic interventions on quality of life (QoL) among breast cancer patients is vital. The purpose of this systematic review was to investigate therapies that target patients with breast cancer’s health-related QoL (HRQoL). The literature search was carried out in the Cochrane, Medline, Embase, and CINAHL databases and PubMed between January 2015 and March 2023 which included published theses and articles from a variety of national and international databases. To extract pertinent material, the text and abstract of the chosen articles were carefully reviewed and evaluated. By applying the PRISMA guidelines, the Google search engine’s search parameters were expanded to encompass open-access articles, guaranteeing a greater variety of resources for the research. Following the screening of various citations, 284 full-text articles were examined. In the end, 14 articles were included. The reviews emphasized the effectiveness of therapies meant to improve HRQoL in individuals with breast cancer. The physical, psychological, and social domains saw therapeutic effects from these therapies, which resulted in a major improvement in the HRQoL of breast cancer patients. The importance of including different therapies in the treatment of patients with breast cancer is underscored by the persistent evidence of noteworthy enhancements in HRQoL. Overall, the review supports the recommendation for incorporating counseling, psychological interventions, educational programs, and supportive therapies such as progressive muscle relaxation as essential components of comprehensive care for breast cancer patients. By addressing the multidimensional needs of patients, these interventions contribute to improved HRQoL and overall well-being throughout the breast cancer journey.

The enhancement of therapeutic effects of low-intensity ultrasound with spiky and spherical gold nanoparticles on CT26 cell line; an in vitro study

Introduction: The utilization of combination therapy has gained attention in the medical field as it can enhance treatment efficacy while minimizing side effects. Gold nanoparticles (AuNPs) have been identified as a promising candidate for enhancing the bioeffects of ultrasound (US) waves. Objectives: The primary objective of this study was to examine the impact of US irradiation when combined with spiky and spherical AuNPs on CT26 cells. Materials and Methods: Following a tailored composition, we devised and produced AuNPs with spiky and spherical morphologies. The properties of these nanoparticles were assessed using dynamic light scattering (DLS), voltammetry, and transmission electron microscopy (TEM). The CT26 cells were treated with the two types of nanoparticles and subsequently exposed to US radiation (1 W/cm2 , 1 MHz, and 10 minutes). The cytotoxic effects of various therapeutic interventions were assessed using MTT and flow cytometry assays. Results: This study’s findings indicate that nanoparticles’ morphology played a significant role in influencing the antitumor effects of US. Specifically, it was observed that the presence of spiky nanoparticles, when subjected to US, resulted in a significantly higher rate of cell death compared to spherical nanoparticles (P<0.001). Additionally, it was observed that the temperature changes induced by the spiky nanoparticles were comparatively lower. This observation implies that nanoparticles with spiky morphology enhance the non-thermal effects of US waves. Conclusion: The outcomes demonstrate a noteworthy augmentation in the biological impacts, specifically the non-thermal effects of US waves when employed in conjunction with spiky nanoparticles.

In Vitro Dental Plaque Culture Model for Biofilm Structural Analyses.

Extensive research has focused on the compositional changes in dental plaque microbiome communities during the transition from health to disease, known as dysbiosis. However, alterations in the spatial composition of these communities throughout the progression from health to disease remain under-explored. We describe an in vitro dental plaque model for culturing oral biofilms seeded with dental plaque from human volunteers. Our model recapitulates important features of the in vivo environment including shear force induced by salivary flow over teeth and the nutritional milieu experienced by microbes that inhabit the transitional zone between supragingival and subgingival aspects of the teeth. Importantly, our model is amenable to multiplex fluorescent labeling and multispectral imaging for testing specific hypotheses regarding systems-level community structure and function. The model allows for precise manipulation of various environmental conditions, such as flow rate and nutrient availability to investigate their effects on biofilm development and spatial structure. Furthermore, this model can be used to test the effects of various therapeutic interventions, e.g., antimicrobial agents, on the biofilm composition and structure at the micron to millimeter scale, making it a valuable tool for studying the molecular and cellular basis of dental plaque-mediated diseases and for benchmarking new therapeutic interventions. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Dental plaque-on-a-chip in vitro model culture system Support Protocol: Gingival margin (GM) medium preparation Basic Protocol 2: Microcosm labeling and multispectral image acquisition.

Concise review: gamma-glutamyl transferase - evolution from an indiscriminate liver test to a biomarker of cardiometabolic risk

This concise review article critically examines the recent medical literature regarding gamma glutamyl transferase (GGT) with a special emphasis on newly proposed indications for GGT use, including cardiovascular risk assessment. GGT is a ubiquitous glycosylated protein embedded in the outer surface of cell membranes, which catalyzes the transfer of glutamyl groups from various substrates and plays a key role in the antioxidant/pro-oxidant balance. In the past, the enzyme was considered a non-specific liver test. Current evidence supports the role of GGT in the assessment of portal hypertension in cystic fibrosis, porto-sinusoidal vascular disease, malignant mesothelioma, and incident type 2 diabetes and as a biomarker of cardiometabolic risk and cardiovascular disease. Several specific points including the use of GGT in hepatology as a sensitive but poorly specific test and the association of GGT with metabolic syndrome, nonalcoholic fatty liver disease and its fibrotic stages, cardiometabolic risk, chronic kidney disease, neurodegenerative disorders and dementia, idiopathic pulmonary arterial hypertension, and Corona Virus Disease 2019 (COVID-19) are addressed based on the most recent research in these fields. Putative mechanisms linking GGT with increased metabolic stress and the effects of various therapeutic interventions on GGT values are also discussed. We conclude that GGT has evolved from an indiscriminate liver test and an index of alcohol consumption to a biomarker of cardiometabolic health. The proper interpretation of GGT values (i.e., of hepatic vs. extrahepatic origin) is deeply affected by the clinical and epidemiological context. We propose that GGT may be utilized in public health campaigns, in the research arena, and in clinical practice to identify those individuals who can benefit most from the proactive preventive and therapeutic approaches, given that they are at high cardiometabolic risk.

Effect of obesity on assisted reproductive treatment outcomes and its management: a literature review

Key content Obesity is associated with infertility and poor obstetric outcomes. The current trends of advanced maternal age and rising obesity rates contribute indirectly to the growing demand for fertility treatment and assisted reproduction treatment (ART), posing clinical and ethical dilemmas for fertility service providers. The live‐birth rate, after ART, is significantly lower in obese women than non‐obese women, possibly due to impaired oocyte quality and/or defective endometrial receptivity. Poor ART outcomes correlate positively with the severity of obesity. Management of obesity‐related infertility should include diet, exercise, cognitive behavioural interventions and possibly adjunctive pharmacotherapy. Bariatric surgery may benefit morbidly obese women who struggle to lose weight otherwise. Randomised controlled trials are required to clarify the effects of various therapeutic interventions for obesity on ART outcomes. Learning objectives To understand the association of obesity and infertility with ART outcomes. To learn the principles of obesity‐related infertility management. Ethical issues To understand the ethical challenges in the provision of ART for obese women and to inform the stance of professional bodies, such as the British Fertility Society and the European Society of Human Reproduction and Embryology.

Periimplantitis Treatment

Periimplantitis is the most frequent cause of late implant failure; however, little is known about the long-term success of periimplantitis treatment and the effectiveness of various therapeutic interventions. A total of 142 patients were referred to the Academy for Oral Implantology in Vienna for the treatment of recurrent periimplantitis around single-tooth implants. Of them, 72 patients (51%) were treated by laser decontamination, 47 patients (33%) by implantoplasty surgery, and 23 patients (16%) by a combination of both approaches. Overall success of periimplantitis therapy was 89% after 9 years of follow-up, and it did not differ significantly between female and male patients (P = 0.426). The number of implant failures that could not be prevented by periimplantitis treatment was 6 after laser decontamination (8%), 6 after implantoplasty surgery (13%), and 4 after a combination of both therapies (17%). Implant loss occurred after 4.9 ± 1.9 years of therapy, on average. No significant difference between the 3 treatment groups could be observed (P = 0.393). The present results suggest that success rates of periimplantitis therapy with either laser decontamination or surgical implantoplasty are high. These success rates do not appear to be associated with patient gender or treatment strategy.

Disinhibitory Interventions and Voluntary Quadriceps Activation: A Systematic Review

To determine the effects of various therapeutic interventions on increasing voluntary quadriceps muscle activation. Decreased voluntary quadriceps activation is commonly associated with knee injury. Recently, research has focused on developing specific disinhibitory interventions to improve voluntary quadriceps activation; yet, it remains unknown which interventions are most effective in promoting this improvement. We searched Web of Science from January 1, 1965 through September 27, 2012, using the key words quadriceps activation and transcutaneous electrical nerve stimulation, transcranial magnetic stimulation, cryotherapy, focal joint cooling, joint mobilization, joint mobilisation, joint manipulation, manual therapy, and neuromuscular electrical stimulation. Studies evaluating the effect of disinhibitory interventions on volitional quadriceps activation were used in our review. Standardized effect sizes (Cohen d) and 95% confidence intervals (CIs) were calculated from voluntary quadriceps activation means and standard deviations measured at baseline and at all available postintervention time points from each study. Ten studies were grouped into 5 categories based on intervention type: manual therapy (4 studies), transcutaneous electrical nerve stimulation (2 studies), cryotherapy (2 studies), neuromuscular electrical stimulation (2 studies), and transcranial magnetic stimulation (1 study). Transcutaneous electrical nerve stimulation demonstrated the strongest immediate effects (d = 1.03; 95% CI = 0.06, 1.92) and long-term effects (d = 1.93; 95% CI = 0.91, 2.83). Cryotherapy (d = 0.76; 95% CI = -0.13, 1.59) and transcranial magnetic stimulation (d = 0.54; 95% CI = -0.33, 1.37) had moderate immediate effects in improving voluntary quadriceps activation, whereas manual therapy (d = 0.38; 95% CI = -0.35, 1.09) elicited only weak immediate effects. Neuromuscular electrical stimulation produced weak negative to strong positive effects (range of d values = -0.50 to 1.87) over a period of 3 weeks to 6 months. Transcutaneous electrical nerve stimulation demonstrated the strongest and most consistent effects in increasing voluntary quadriceps activation and may be the best disinhibitory intervention for improving the same.

Isokinetic Testing in Patients with Neuromuscular Diseases

This literature review aimed to study the use of isokinetic testing in patients with neuromuscular diseases (NMDs) and to identify directions for future research of isokinetic testing. The MEDLINE (January 1, 1965, to July 1, 2010), Cumulative Index to Nursing and Allied Health (1980 to May 2010), and Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2009) electronic databases were searched. The literature search was conducted using the keywords muscle assessment, muscle strength, evaluation, isokinetic, neuromuscular diseases, muscle fatigue, functional test, rehabilitation, and literature search. Relevant references cited in the selected articles were also considered, regardless of the year of publication. The search strategy yielded 13 articles involving a variety of patients with known NMDs. All studies demonstrated that isokinetic dynamometry is appropriate and safe for ambulatory patients with NMDs. Isokinetic testing has proven to be reliable (intratest/intertest correlation coefficient ranged from 0.65 to 0.98), with the proximal muscles having the highest reliability, and sensitive to disease progression and to the effects of various therapeutic interventions. However, isokinetic testing has never gained wide acceptance, partly because of concerns about stabilizing the dynamometer and the subject during the test and of the lack of standardized protocols for isokinetic strength measurement. Isokinetic testing is an important part of the comprehensive evaluation and rehabilitation of patients with NMD. Research has demonstrated its efficacy in providing clinically relevant information. When integrated with a complete history, physical examination, and functional evaluation, isokinetic testing and exercise can be a valuable tool for the clinician in the assessment, rehabilitation, and performance enhancement of patients with NMD. Such equipment, however, has several disadvantages, rendering it usually impractical in the clinical setting.

Neuroimaging in Parkinson's disease.

Parkinson's disease (PD) is a common disorder in which the primary features can be related to dopamine deficiency. Changes on structural imaging are limited, but a wealth of abnormalities can be detected using positron emission tomography, single photon emission computed tomography, or functional magnetic resonance imaging to detect changes in neurochemical pathology or functional connectivity. The changes detected on these studies may reflect the disease process itself and/or compensatory responses to the disease, or they may arise in association with disease- and/or treatment-related complications. This review will focus mainly on neurochemical and metabolic studies and reviews various approaches to the assessment of dopaminergic function as well as the function of other neurotransmitters that may be affected in PD. A number of clinical applications are highlighted, including diagnostic utility, identification of preclinical disease, changes associated with motor and nonmotor complications of PD, and the effects of various therapeutic interventions.

Wilson′s disease: An Indian perspective

Wilson's disease (WD) is an autosomal recessive disease involving a defect of copper transport by the hepatic lysosomes. It leads to excess copper deposition in the liver, the brain, the kidneys and the skeletal system, affecting most commonly children or young adults and running an invariably fatal course if not adequately treated by de-coppering therapy. The last century has witnessed several changes, notable among these are: Increased awareness, improved diagnostic facilities leading to earlier recognition even in the pre-symptomatic phase, clear distinction from its mimics, aggressive therapeutic approaches owing to availability of effective treatment and an overall reduction in the morbidity and mortality. It is widely acknowledged that the disease is not as rare as once believed. Sir SAK Wilson published his landmark article in 1912, but it was only in 1968 that the first patient of WD was reported from our country. Publications from India on WD have focused on phenotypic characterization, documentations of lesser recognized aspects of the disease e.g. seizures, behavior abnormality, speech and cognitive impairment, sub-clinical affection of visual pathway, heart and autonomic function and pre-symptomatic detection. Attempts have been made to understand the clinical heterogeneity of the disease through identification of biochemical and immunological markers, magnetic resonance imaging, neuropathological study and genetic analysis for novel and/or known mutations. Assessment of impairment and severity and effect of various therapeutic interventions namely zinc sulphate on the long-term outcome and quality of life have also been studied. Nevertheless, clinicians often face difficulties in long-term care of these patients. Diagnostic errors leading to delay in diagnosis and initiation of treatment are common, even in patients with positive family history. There is no consensus regarding therapeutic protocols since the use of penicillamine, once a 'gold standard' for treatment, has been debated by experts. Mortality and morbidity of this potentially treatable disease and nonavailability of medications to the poor patients remain a major area of concern.

MO‐C‐AUD‐01: The Emerging Role of Imaging as a Biomarker for Response

Radiologic images have been used for decades to gauge the effectiveness of various therapeutic interventions. In the areas of oncology, cardiovascular disease, neurology, arthritis and osteoporosis, imaging plays a vital role in decision‐making regarding effectiveness of therapy for an individual patient. Increasingly, imaging also is being utilized during all phases of therapeutic drug development, resulting in speedier drug discovery and, in some instances, ensuring a drug's safety. There has been an “explosion” in use of biomarkers in drug discovery.Many imaging biomarkers are already commonly used, such as tumor size measured at CT to reflect tumor burden;T2 hyperintensity detected at brain MR imaging to reflect the burden of Multiple Sclerosis; and bone density determined on DEXA studies to assess for osteoporosis. One major benefit of imaging biomarkers is that the findings may be evaluated and quantified for changes over time. Newer imaging biomarkers are also playing a role in drug discovery, such as dynamic contrast‐enhanced MR imaging to assess for vascular flow to tumors; molecular imaging in the functional evaluation of cardiac, neurologic and oncologic processes; and CT in the evaluation of cystic fibrosis. The complexity in imaging biomarkers is increasing not only with the number of available imaging and post‐processing techniques, but perhaps even more importantly, with the number and diversity of relevant therapeutic options. Increasingly, it is becoming clear that a single imaging biomarker alone can be misleading, but is more robust when combined with other imaging or non‐imaging biomarkers.Educational Objectives:1. Understand the role of imaging in monitoring response to therapy.2. Understand the issues and clinical complications of imaging as a biomarker.Research sponsored by Astrazeneca Corporation.

A Functional Floxed Allele of Pkd1 that Can Be Conditionally Inactivated In Vivo

Gene targeting has been used to create a variety of lines of mice with Pkd1 mutations that share many common features. Homozygous Pkd1 mutants invariably develop pancreatic and renal cysts if they survive to day 15.5 post coitum and die in either the fetal or the perinatal period. In contrast, mice with heterozygous mutations of Pkd1 are generally normal and have few if any renal cysts. These features have limited the utility of these models as tools to study the pathogenesis of cyst formation and the effect of various therapeutic interventions on disease progression. This report describes a new line of mice with a floxed allele of Pkd1 (Pkd1(cond)) that has an FRT-flanked neomycin cassette inserted into intron 1 and lox P sites inserted into intron 1 and intron 4. The Pkd1(cond) allele is fully functional, and homozygotes are viable and healthy. It is shown that the lox P and FRT sites can be selectively induced to recombine to produce two new alleles, Pkd1(del2-4) and Pkd1(cond-Deltaneo), by crossing to animals that express either the cre or FLPe recombinase, respectively. It is found that Pkd1(del2-4) allele functions as a true null, whereas presence or absence of the neomycin gene has no functional effects. It also is shown that somatic loss of Pkd1 results in renal and hepatic cysts. This new line of mice will be invaluable in the study of Pkd1 biology and serve as a powerful new tool that can be used to study the pathogenesis of autosomal dominant polycystic kidney disease.

Murine models of polycystic kidney disease: molecular and therapeutic insights

Numerous murine (mouse and rat) models of polycystic kidney disease (PKD) have been described in which the mutant phenotype results from a spontaneous mutation or engineering via chemical mutagenesis, transgenic technologies, or gene-specific targeting in mouse orthologs of human PKD genes. These murine phenotypes closely resemble human PKD, with common abnormalities observed in tubular epithelia, the interstitial compartment, and the extracellular matrix of cystic kidneys. In both human and murine PKD, genetic background appears to modulate the renal cystic phenotype. In murine models, these putative modifying effects have been dissected into discrete factors called quantitative trait loci and genetically mapped. Several lines of experimental evidence support the hypothesis that PKD genes and their modifiers may define pathways involved in cystogenesis and PKD progression. Among the various pathway abnormalities described in murine PKD, recent provocative data indicate that structural and/or functional defects in the primary apical cilia of tubular epithelia may play a key role in PKD pathogenesis. This review describes the most widely studied murine models; highlights the data regarding specific gene defects and genetic modifiers; summarizes the data from these models that have advanced our understanding of PKD pathogenesis; and examines the effect of various therapeutic interventions in murine PKD.

Nephroprotection in Diabetes Mellitus

Present study analyses nephroprotective effect of various therapeutic interventions at different stages of kidney involvement in diabetes mellitus. A MEDLINE search of past 10 years data on various experimental studies, controlled clinical trials, meta-analysis and editorials pertaining to nephroprotection in diabetes mellitus was made. Effect of various therapeutic interventions such as metabolic glycaemic control, restricted protein diet and antihypertensive drugs (especially ACE inhibitors) has been analysed on the progression of different stages of kidney involvement in diabetes mellitus such as normoalbuminuria, microalbuminuria, diabetic nephropathy and end stage renal disease (ESRD). An attempt has been made to analyse differential long-term impact of various therapeutic interventions in relation to type of diabetes mellitus (i.e., IDDM and NIDDM) and associated hypertension. Progression of IDDM patients having microalbuminuria or diabetic nephropathy with or without hypertension has improved during the past decade largely because of adequate glycaemic control and effective antihypertensive treatment with conventional drugs e.g. beta-blockers and calcium antagonists, and more so due to the use of ACE inhibitors e.g. captopril, enalapril etc. Superiority of ACE inhibitor tends to decline from normotensive stage to the degree of rise in systemic blood pressure. However, data in NIDDM patients suffering from diabetic nephropathy is incomplete and inconclusive.

Metabolic tissue characterization in the failing heart by positron emission tomography.

Congestive heart failure represents an important clinical issue which can benefit from newer imaging approaches. Use of radiolabelled pharmaceuticals allow for functional tissue characterization in patients with impaired left ventricular function. Assessment of regional myocardial perfusion and metabolism with either SPECT or PET methods provide accurate detection of tissue viability. Several studies have indicated the utility of these imaging approaches for improved selection of patients for revascularization. The combination of functional measurements with echocardiography and metabolic tissue characterization with PET allows for the non-invasive measurement of cardiac efficiency. The effect of various therapeutic interventions can be objectively assessed by a work-metabolic index. Finally, autonomic innervation of the heart plays an important role in the modulation of the haemodynamic performance of the failing heart. New imaging approaches using radiolabelled catecholamine analogues or receptor antagonists have been used to identify the integrity of myocardiac pre- and post-synaptic sympathetic innervation. Imaging results in patients with dilated cardiomyopathy not only demonstrated a down-regulation of beta-receptor density, but also an abnormal pre-synaptic neuronal function, which may result into impaired regulation of extraneuronal catecholamine concentration. Thus, advanced scintigraphic imaging approaches may improve our diagnostic and prognostic workup in patients with congestive heart failure and may provide objective endpoints for the assessment of therapy.

Drug utilisation studies as tools in health economics.

Drug utilisation and many pharmacoeconomic studies use pharmacoepidemiological methods characterised by the study of drugs from a socioeconomic perspective. Drug utilisation studies may be defined as studies of the marketing, distribution, prescription and use of drugs in a society, with special emphasis on the resulting medical, social and economic consequences. Pharmacoeconomic studies are used to measure drug efficiency, through comparison of the costs and effects of alternative therapies. Drug utilisation studies can provide highly valuable information, at a reasonable price, on the costs and effects (harmful and beneficial) of drugs. Such studies make available much useful information including indirect data on morbidity, the pharmaceutical component of the treatment cost of an illness, therapeutic compliance, the incidence of adverse reactions, the effectiveness of drug consumption and the choice of comparators. This information can be of great use in the subsequent elaboration of pharmacoeconomic studies, or in the selection of problematic areas in which these studies may be applied. Pharmacoeconomic studies, in turn, can be used to discover the economic repercussions of inappropriate prescribing and to quantify the cost effectiveness of various therapeutic interventions. The use of drug utilisation studies in conjunction with pharmacoeconomic analysis can result in more cost effective utilisation of medicines and a better utilisation of pharmacoeconomic methods, both of which contribute to a more rational use of drugs.

Assessment of myocardial fatty acid metabolism with 1-11C-palmitate.

The myocardium has the capacity to utilize a variety of metabolic substrates, including long-chain fatty acids, ketone bodies, glucose, lactate, and amino acids. Under most conditions long-chain fatty acids constitute the major myocardial energy source. Imaging of long-chain fatty acids can be accomplished with carbon 11-labeled palmitate (1-11C-palmitate) and positron emission tomography. Imaging can be performed in either static or dynamic modes. In normal subjects accumulation of the tracer is homogeneous throughout the heart. In patients with myocardial infarction, distinct defects in accumulation are seen. In dilated cardiomyopathy, uptake is spatially heterogeneous. Clearance of 1-11C-palmitate in normal myocardium is biexponential and homogeneous throughout the heart. Administration of glucose, or feeding, decreases uptake of the tracer into the early rapid turnover pool and decreases clearance of the tracer from that pool. In normal myocardium atrial pacing increases the rate of clearance; in ischemic myocardium the degree of increased clearance is attenuated. In patients with cardiomyopathy caused by long-chain fatty acid coenzyme A dehydrogenase deficiency, 1-11C-palmitate clearance is diminished compared with total myocardial oxygen consumption traced with carbon 11-labeled acetate. Thus positron emission tomography with 1-11C-palmitate permits assessment of patients with ischemic heart disease and cardiomyopathy of diverse causes, providing insights into both pathophysiologic mechanisms and the effectiveness of various therapeutic interventions.

Morphology of global cerebral ischemia.

The cerebral tissue responses to ischemia are modified by many factors, including the mechanism by which ischemia is induced, and the severity and duration. Children can withstand brain ischemic insults that are usually lethal to older patients. Other modifying factors of ischemia, such as barbiturates and serum glucose, remain poorly defined in humans. Once a cerebral ischemic event occurs, for example, after cardiac arrest and resuscitation, secondary events (such as alterations in the perfusability and reactivity of the microcirculation) may aggravate the original ischemic injury at discrete sites of the brain. A more exact definition of a) the limits of reversibility of ischemic injury, b) the histologic features of sublethally injured tissues, and c) the effects of various therapeutic interventions, awaits the development of relatively inexpensive and reproducible animal models of ischemia in which objective comparisons can be made between the nature of the local circulatory conditions and the accompanying histologic abnormalities.